into a broad range of micellar, rod-like, bicontinuous, and liquid-crystalline complex fluids, which have myriad biological, materials, and product applications. However, amphiphilic self-assembly is not limited to aqueous systems. We have explored the self- assembly of surfactants in anhydrous sugars. Our study reveals that anhydrous powders of sugars and surfactants suspended in oil spontaneously form molten microemulsion glasses with nanometer-size domains of sugar and liquid oil without mixing. The low cost, water solubility, low toxicity and stabilizing properties of glassy sugars make them ideal water replacements for many pharmaceutical, food and materials synthesis applications. The optical clarity and solid appearance of these glasses at room temperature belie their inclusion of more than 50% (vol.) oil, which confers liquid-like diffusivity.

We have also investigated the phase behavior and characterization studies of edible microemulsions of d-limonene (orange oil) with concentrated sugar solutions (>65 wt%) using sucrose laurate and sucrose oleate as surfactants. The phase behavior of these mixtures is studied as a function of temperature and surfactant composition, identifying the specific effects of sugar concentration, surfactant chain length, and oil loading on the formation of microemulsion and lamellar phases. Small-angle neutron scattering experiments confirm the presence of well-structured microemulsions with domain sizes ranging from ~35 to 60 nm. With few exceptions, the patterns of microemulsion phase behavior with concentrated sugar solutions are very similar to that of aqueous systems.

These studies simulate the effect of either increasing sugar concentrations or removing

iii water (e.g. spray drying) on the one phase microemulsion region. In addition to providing better understanding of the underlying phenomena of formation of sugar based microemulsion glasses, these aqueous sugar based microemulsions have potential applications in encapsulation of hydrophobic and hydrophilic actives, which are used in food, pharmaceuticals and many other industries.

Acknowledgements

I take this opportunity to express my thanks and gratitude to my advisor, Dr. Carlos

Co, for his continuous guidance and support during my graduate studies at University of

Cincinnati. I would also like to thank my Ph.D. committee members, Dr. Chia-Chi Ho,

Dr. Gerald B. Kasting and Dr. Steve Clarson for their valuable suggestions during my

Ph.D. research.

I am grateful to Dr. Jing-Huei Lee and Dr. Matthew Liberatore for their successful collaborative research efforts on characterization of sugar-oil glasses using self-diffusion coefficient measurements and rheological measurements respectively.

I would like to thank my lab mates – Dr. Girish kumar, Dr. Feng Gao, Weiyi Li,

Stephen Fenimore and Brian Shoop for their help and making my graduate study experience unique and memorable.

I am deeply grateful to one of my best friends and lab mate, Dr. Dan Wu, for her support and guidance during this Ph.D. research work. Her suggestions and support provided a solid backbone to keep myself motivated and focused during the difficult periods of my Ph.D. research.

There are no words to express my gratitude to my beloved parents (Rajeshkumar

Dave and Aruna Dave) and my brother (Kirtesh Dave) and sister-in-law (Bhavisha

Dave) for their love, support, care, and encouragement during the five years of my graduate studies.

I would like to acknowledge the Givaudan Flavors Corporation and National Science

Foundation (NSF) for providing the funding support during this research work.

v Table of Contents

Abstract…...... iii

Acknowledgements ...... v

List of Figures...... ix

List of Abbreviations ...... xvi

Chapter 1 Introduction...... 1

1.1 Dissertation Outline ...... 3

Chapter 2 Background ...... 4

2.1 Surfactant ...... 4

2.2 Surfactant Self-Assembly ...... 4

2.2.1 Morphologies of Self-Assembled Aggregates...... 5

2.3 Sugar Based Surfactants ...... 12

2.3.1 Comparison of Sugar Based Surfactants to Petroleum Based Nonionic

Surfactants...... 12

2.3.2 Phase Behavior of Sugar Based Microemulsions ...... 13

2.3.2.1 General Patterns of Nonionic Microemulsions Phase Behavior...... 14

2.3.2.2 Alkyl polyglucoside (APG) Surfactant Based Microemulsions ...... 20

2.3.2.3 Sucrose Ester Surfactant Based Microemulsions ...... 24

2.3.2.4 Sugar Based Nonaqueous Microemulsions ...... 28

Chapter 3 Experimental Section...... 40

3.1 Introduction...... 40

3.2 Sugar Based Aqueous Microemulsions ...... 40

3.2.1 Materials ...... 40

vi 3.2.2 Phase Diagram Determination ...... 42

3.2.2.1 Microemulsion Sample Preparation...... 42

3.2.3 Neutron Scattering ...... 43

3.3 Sugar Based Non-aqueous Microemulsions ...... 45

3.3.1 Materials ...... 45

3.3.2 Phase Diagram Determination ...... 45

3.3.2.1 Microemulsion Glass Sample Preparation...... 45

3.3.3 Neutron Scattering ...... 47

3.3.4 Modulated Differential Scanning Calorimetry (MDSC) ...... 48

3.3.5 Rheometry...... 48

3.3.6 Magnetic Resonance Imaging...... 48

3.3.7 Scanning Electron Microscopy...... 49

Chapter 4 Sugar Based Aqueous Microemulsions...... 50

4.1 Summary...... 50

4.2 Introduction...... 50

4.3 Results...... 51

4.3.1 Effects of Increasing Sugar Concentration ...... 51

4.3.2 Effects of Surfactant Alkyl Chain Length ...... 54

4.3.2.1 Sucrose Ester Surfactants...... 54

4.3.2.2 Alkyl Polyglucoside Surfactants...... 57

4.3.3 Compensatory Effects of Sugar Concentration and Surfactant Alkyl Chain

Length…...... 57

4.3.4 Effects of Varying Oil Loading ...... 60

vii 4.3.5 Effects of Increasing Surfactant Concentration On Microemulsion

Structure...... 60

4.4 Discussion...... 66

4.5 Conclusions...... 67

Chapter 5 Sugar Based Non-aqueous Microemulsions ...... 68

5.1 Summary...... 68

5.2 Introduction...... 68

5.3 Results and Discussion ...... 69

5.3.1 Spontaneous Formation of Anhydrous Microemulsion Glasses...... 69

5.3.2 Phase Behavior of Anhydrous Microemulsion Glasses...... 71

5.3.3 Characterization of Anhydrous Microemulsion Glasses ...... 73

5.3.3.1 Small Angle Neutron Scattering (SANS) ...... 73

5.3.3.2 Self-Diffusion Coefficient Measurements (Using MRI) ...... 77

5.3.3.3 Rheology...... 82

5.3.3.4 Glass Transition Temperature Measurements (Using MDSC)...... 82

5.3.3.5 Scanning Electron Microscopy (SEM) Imaging...... 84

5.4 Conclusions...... 88

Chapter 6 Conclusions...... 90

6.1 Sugar Based Aqueous Microemulsions ...... 90

6.2 Sugar Based Non-aqueous Microemulsions ...... 91

Chapter 7 Proposed Future Work...... 92

Bibliography ...... 93

viii List of Figures

Figure 2.1 Non-ionic surfactant, water and oil mixture self-assembles into rich variety of

nanostructures10...... 6

15 Figure 2.2 Illustration of surfactant packing number, =ν / 0lap c ...... 9

Figure 2.3 Surfactant packing number of surfactant molecules and corresponding optimal

aggregated structure for geometrical packing reasons7...... 10

Figure 2.4 Radii of curvature perpendicular to the surfactant film of aggregate structures14...... 11

Figure 2.5 Phase diagrams of three corresponding binary mixtures of the ternary mixtures

of water, oil and nonionic surfactant (adapted from Kahlweit et al.)32...... 16

Figure 2.6 Ternary phase prism of water, oil and nonionic surfactant with increasing

temperature37...... 17

Figure 2.7 Fish cut section through the phase prism of ternary mixtures of water, oil and

nonionic surfactant containing equal masses of oil and water29...... 19

Figure 2.8 Fish cut section through the phase prism of quarternary mixtures of water,

octane, C6E2 and C10βG1 with varying C10βG1 concentration (δ) containing equal masses

of octane and water60...... 22

60 Figure 2.9 Binary phase diagram of C9βG1 and C3OC2OC3 ...... 23

Figure 2.10 Fish cut through the phase prism of the ternary mixtures of water–

52 CkOC2OCk–C8βG1 containing equal amount of water and oil ...... 25

Figure 2.11 Fish cuts through the phase prism of the quarternary mixtures of water-

decane-sucrose monododecanoate-hexanol at increasing temperature progression

containing equal amount of water and oil83...... 27

ix Figure 2.12 Fish cut through the phase prism of the quarternary mixtures of glycerol-

propylene glycol-dodecane-C12E5 with increasing mass fraction of glycerol in polar

organic mixtures (y)92...... 30

Figure 2.13 Effect of solvophobicity of oil on fish cuts through the phase prism of the

quarternary mixtures of glycerol-propylene glycol-dodecane-C12E5 with increasing mass

fraction of glycerol in polar organic mixtures (y)92...... 31

Figure 2.14 Comparison of fish cuts through the phase prism of the ternary mixtures of formamide-octane-C18E6 (shown by solid line) and water-octane-C12E4 (shown by dotted

line) with increasing temperature and surfactant concentration94...... 32

Figure 2.15 Fish cuts through the phase prism of the mixtures of aqueous sugar solutions,

isobutylacrylate, C8G1 and C12G1 as surfactants, and 1,2 octanediol as cosurfactants

containing equal amount of sugar and isobutylacrylate oil5...... 34

Figure 2.16 Anhydrous microemulsion glass prepared by controlled dessication of the

75% sugar solution based microemulsions (shown by the star in Figure 2.15) containing

equal amount of sugar and isobutylacrylate oil5...... 35

Figure 2.17 Modulated differential scanning calorimetry (MDSC) measurements of the

microemulsion glasses prepared by controlled desiccation of liquid microemulsions

prepared from a 75% sugar solution with divinylbenzene mass loading (α) varies from 50

wt% to 80 wt% at constant surfactant concentration (γ) of 22.5 wt%6...... 37

Figure 2.18 Small angle neutron scattering (SANS) measurements of the sugar based

microemulsion glasses before and after polymerization of divinlbenzene oil.

Microemulsion glasses were prepared by controlled desiccation of liquid microemulsions

x prepared from a 75% sugar solution with divinylbenzene mass loading (α) varies from 50

wt% to 70 wt% at constant surfactant concentration (γ) of 22.5 wt%6...... 38

Figure 4.1 Phase diagram of aqueous mixtures of sugar, limonene, sugar ester surfactants

showing the progression of phase behavior with increasing sugar concentration.

Markings identify temperature and composition of microemulsion and liquid crystalline

samples probed with SANS (Figure 4.3)...... 52

Figure 4.2 Phase diagram of aqueous mixtures of sugar, limonene, sugar ester surfactants

showing the progression of phase behavior with further increase in sugar concentration.

Not shown is a small one phase lamellar region present above 9% surfactant for 80%

sugar...... 53

Figure 4.3 SANS spectra of microemulsion and lamellar phase samples marked in Figure

1. Solid line fitted to the microemulsion SANS spectra is calculated from the Teubner-

Strey model. SANS measurements performed at NIST...... 55

Figure 4.4 Phase diagram of aqueous mixtures of sugar, limonene, sugar ester surfactants

showing the progression of phase behavior with varying ratio of sucrose oleate and

sucrose laurate surfactants...... 56

Figure 4.5 Phase diagram of aqueous mixtures of sugar, limonene, alkyl polyglucoside

surfactants showing the progression of phase behavior with varying ratio of C8G1 and

C12G1 surfactants...... 58

Figure 4.6 Phase diagram of aqueous mixtures of sugar, limonene, sugar ester surfactants

showing the compensatory adjustment of long to short chain surfactant ratio to

accommodate different sugar concentrations...... 59

xi Figure 4.7 Phase diagram of aqueous mixtures of sugar, limonene, sugar ester surfactants

showing the progression of phase behavior with varying oil loading. Very slow phase

separation precluded precise determination of lower boundaries for the lamellar and

microemulsion phases at 30% oil loading...... 61

Figure 4.8 Adjusting the sucrose oleate:sucrose laurate ratio for 30% oil loading from

50:50 to 40:60 shifts the microemulsion and lamellar regions upwards, allowing for

precise determination of lower phase boundaries...... 62

Figure 4.9 Phase diagram and composition-temperature of microemulsions samples

probed with SANS (Figure 4.10)...... 63

Figure 4.10 SANS spectra of concentrated sugars, d-limonene and surfactant mixtures

(Figure 8) showing the effect of increasing surfactant concentration. Symbols and lines

represent measured and model calculated intensities, respectively...... 64

Figure 4.11 Variation of domain size with increasing surfactant concentration...... 65

Figure 5.1 Spontaneous formation of a microemulsion glass. Sugar and surfactant powder dried to 99.5% dryness dispersed in oil at room temperature “dissolves” upon heating to 365 K to form a one phase molten microemulsion glass. The composition here corresponds to sample C in the phase diagram shown in Figure 5.2. Gradual cooling of the molten glass to room temperature yields a solid microemulsion glass (left) containing

~52 vol% liquid oil with a Mohs hardness of 0.7...... 70

Figure 5.2 Phase diagrams for molten sugar – limonene microemulsion glasses at 365 K.

Multiple phases are present above and below the boundaries delineating the one phase

(1φ) microemulsion region. (a) Phase diagram for 50:50 limonene oil to sugar mass ratio

corresponding to α=50%. Letter symbols correspond to compositions probed by small

xii angle neutron scattering (Figure 5.3) and magnetic resonance imaging (Figure 5.4). (b)

Phase diagram at fixed overall surfactant loading of γ=20%. Square symbols for phase boundaries at low oil loadings (α≤0.3) were estimated from samples prepared heated briefly to 400 K then observed at 365 K. Room temperature self-diffusion coefficients of limonene oil present in the interstices of the microemulsion glasses measured by MRI

(Figure 5.4) are shown for compositions marked by stars. For comparison, the self- diffusion coefficient of pure limonene measured under identical conditions was 1.3×10-5 cm2/s...... 72

Figure 5.3 Comparison of phase diagrams of molten sugar – limonene microemulsion glasses at 365 K with varying sugars ratio of sucrose:trehalose from 50:50 to 40:60 and

60:40 (volume basis). Multiple phases are present above and below the boundaries delineating the one phase (1φ) microemulsion region. Star symbols correspond to compositions probed by small angle neutron scattering (Figure 5.6 and Figure 5.7) and values indicate the self-diffusion coefficient values of microemulsion glasses measured by magnetic resonance imaging along the middle composition point...... 74

Figure 5.4 SANS spectra of solid microemulsion glasses at room temperature corresponding to compositions F, E, and C in the phase diagram shown in Figure 5.2a.

Solid lines are fits to the Teubner-Strey model. which yield domain sizes (d) ranging from 25 to 28 nm and correlation lengths (ζ) of ~10 nm...... 75

Figure 5.5 SANS spectra of solid microemulsion glasses at room temperature corresponding to compositions B, C, and D in the phase diagram shown in Figure 5.2a.

Solid lines are fits to the Teubner-Strey model. which yield domain sizes (d) ranging from 22 to 25 nm and correlation lengths (ζ) of ~10 nm...... 76

xiii Figure 5.6 Variation of domain size of microemulsion glasses with increasing surfactant concentration of the composition points F, E and C in Figure 5.2(a)...... 78

Figure 5.7 SANS spectra of solid microemulsion glasses at room temperature corresponding to compositions shown by the star in the phase diagram shown in Figure

5.3 containing sucrose to trehalose ratio of 60:40 on volume basis. Solid lines are fits to the Teubner-Strey model. which yield domain sizes (d) ranging from 22 to 27 nm and correlation lengths (ζ) of ~10 nm...... 79

Figure 5.8 SANS spectra of solid microemulsion glasses at room temperature corresponding to compositions shown by the star in the phase diagram shown in Figure

5.3 containing sucrose to trehalose ratio of 40:60 on volume basis. Solid lines are fits to the Teubner-Strey model. which yield domain sizes (d) ranging from 24 to 28 nm and correlation lengths (ζ) of ~10 nm...... 80

The self-diffusion measurements were performed using a conventional spin-echo pulse sequence. (c) The slope of the normalized spin echo intensity relative to the field gradient (g), gradient duration (δ), time delay (Δ), and proton gyromagnetic ratio (γ) as shown here for sample C (Figure 5.2a) yields a room temperature self-diffusion coefficient of 6.3×10-6 cm2/s...... 81

xiv Figure 5.10 Master curve of the elastic and viscous moduli for sample C (Figure 5.2a) by

time-temperature superposition using the Williams-Landel-Ferry (WLF) equation...... 83

Figure 5.11 Reversible heat capacity and midpoint heating glass transition temperatures

of microemulsion glasses within the one phase channel (Fig. 2b) for varying oil loadings

(α)...... 85

Figure 5.12 Effect of increasing trehalose fraction (from sucrose:trehalose volume ratio of 50:50 to sucrose:trehalose ratio of 40:60) on the glass transition temperature of

microemulsion glass...... 86

Figure 5.13 SEM image of the vacuum dried microemulsion glass shown in Figure 1... 87

xv List of Abbreviations

Symbol Description

α Mass fraction of oil on a surfactant-free basis

b Incoherent background scattering

CMC Critical micelle concentration

Cp Sample heat capacity

cpα Upper critical point at low temperature Tα

cpβ Lower critical point at high temperature Tβ

dTS Characteristic domain size in Teubner-Strey model

ε Mass fraction of short chain surfactant in the surfactant mixtures

γ Overall mass fraction of surfactant in the mixture

I(q) Experimental scattering intensity

λ Wave length of neutron q Scattering vector

SANS Small Angle Neutron Scattering

Tg Glass transition temperature

ξTS Correlation length in Teubner-Strey model

xvi Chapter 1 Introduction

In aqueous systems, hydrophobic effect drives the self assembly of amphiphiles into a rich variety of nanostructures ranging from micellar, rod-like micellar, bicontinuous and various liquid crystalline phases. Among these self-assembled structures, microemulsions are thermodynamically stable one phase mixtures of water, oil, surfactant, and cosurfactants. They can form oil in water micellar structures at low oil concentration, bicontinuous networks at intermediate oil concentrations, and water in oil reverse micellar structures at higher oil concentrations. Due to this wide range of microstructures, microemulsions are widely used in many applications such as detergency, synthesis of nanoparticles1, enhanced oil recovery2, synthesis of polymeric

membranes from bicontinuous structures3, drug delivery4, and as microreactors.

Bicontinuous microemulsions contain continuous domains of oil and water separated by

surfactant film at the interface. Equal amount of oil and water can facilitate the formation

of bicontinuous structures. However, we have found that bicontinuous microemulsions

can form up to 30 wt% to 60 wt% oil loadings in sugar based microemulsions. This

thesis discusses our investigations on phase behavior of bicontinuous microemulsion regions of sugar based aqueous and non-aqueous microemulsions. Gao and coworkers5, 6

have proposed the controlled desiccation approach to form anhydrous sugar based

microemulsion glasses. However, due to the practical limitation of diffusion based

control desiccation approach and inconsistent neutron scattering data of the sugar glasses

prepared by controlled desiccation, it is required to investigate new approach to form

sugar based microemulsion glasses.

1 We have investigated sugar based aqueous and non-aqueous microemulsions by replacing water in traditional microemulsion with either concentrated sugar solutions or with anhydrous powder of sugars. The principle motivation of investigating sugar based aqueous microemulsions is to understand the underlying phenomena of formation of anhydrous microemulsion glasses by systematically replacing water in traditional microemulsions with anhydrous sugar powder. Phase behavior studies of sugar based aqueous microemulsions simulate the effect of either increasing sugar concentrations or removing water (e.g. spray drying) on the one phase microemulsion region. Thus, these studies provide us valuable information about the types of structural transition occurring during the spray drying processes and the factors responsible for the loss of active ingredients during the spray drying. In addition, these aqueous sugar based microemulsions have potential applications in encapsulation of hydrophobic and hydrophilic actives, which are used in food, pharmaceuticals and many other industries.

Motivation of studying non-aqueous microemulsion glasses has come from their broad practical applications. These sugar-oil glasses do not contain any water and thus, non-aqueous self-assembly approach can certainly provide a possible alternative to many spray and freeze drying processes. Primary ingredient of these sugar-oil glasses is sugar.

The low cost, water solubility, low toxicity and stabilizing properties of glassy sugars make them ideal water replacements for many pharmaceutical, food and materials synthesis applications.

2 1.1 Dissertation Outline

This dissertation discusses detailed phase behavior and microstructure studies of

sugar based aqueous and non-aqueous microemulsions. The dissertation is organized in

seven chapters including the introductory chapter.

Chapter 2 provides the necessary information about self-assembly phenomena and

general phase behavior patterns of nonionic surfactant based on water – oil - CiEj surfactants. This general phase behavior pattern provides a basis for comparison with phase behavior studies of sugar based surfactants (alkyl polyglucosides and sucrose esters) and studies covered during this dissertation research work. Previous findings on sugar based microemulsion glasses have been discussed

Chapter 3 briefly describes the materials, experimental and sample preparation methods, and characterization techniques used.

Chapter 4 explores the phase behavior of the sugar based aqueous microemulsion, studied as a function of temperature and surfactant composition, identifying the specific effects of sugar concentration, surfactant chain length, and oil loading on the formation of microemulsion and lamellar phases.

Chapter 5 presents the self-assembly of surfactants in sugar based non-aqueous microemulsion glasses.

3 Chapter 2 Background

2.1 Surfactant

Surfactant is an abbreviation for the term “Surface Active Agent”. They are adsorbed at variety of surfaces (e.g. solid-vapor and liquid-vapor) and interfaces (e.g. solid-liquid,

solid-solid and liquid-liquid). Surfactants change the properties of these surfaces and

interfaces. Thus, they are called surface active7. Surfactant molecules contain

hydrophobic tail (soluble in non-polar solvents) and hydrophilic head group (soluble in

polar solvents such as water). Due to their amphiphilic nature, surfactants can co-

solubilize non-polar solvents and polar solvents such as oil and water respectively.

Surfactants are classified based on the charge of the polar head groups. Head groups can

be anionic (e.g., sulfate, phosphate, carboxylate), cationic (e.g., quaternary ammonium),

zwitterionic (e.g., betaine), or nonionic (polyether, carbohydrate)8. These surfactants are

widely used in home and personal care industries, cosmetics, pharmaceuticals, textiles, fibers, food industry, paints, plastics, pesticides, and in the oil industries.

2.2 Surfactant Self-Assembly

Surfactant self-assembly is manifestation of the hydrophobic effects9 that prevail in the

mixture of surfactant and polar and/or non-polar solvents. At low surfactant

concentration, there is almost no orientation of the surfactant molecules at the interface

and they lie flat on the interface. Further increasing the surfactant concentration,

surfactant molecules cover the entire interface by a unimolecular layer. The

concentration at which surfactant molecules occupy the entire interface is called the

4 critical micelle concentration (CMC). Above CMC, surfactant molecules self-assemble into rich variety of nanostructures such as micellar, cylindrical micellar, bicontinuous structure and various liquid crystalline phases. Figure 2.1 illustrates the wide gamut of nanostructures that non-ionic surfactant can form when added into a mixture of polar and non-polar solvents such as oil and water10.

Driving force for the self-assembly in water is the formation of hydrophobic hydration shell around the hydrophobic chain of the surfactant molecule. Classically, it was believed that water forms many hydrogen bonds per unit volume in the hydration shell to undergo the structural enhancement of the shell surrounding the hydrophobic surfactant chain. However, these shells overlap at the time of aggregation and structured water releases accompanied by gain in entropy. Current views suggest that hydrogen bonds of water in hydration shells orient themselves tangentially11 to the hydrophobic surface with accompanied loss of entropy. This tangential alignment does not provide the strong structural enhancement to the hydrophobic hydration shell. However, at a certain surfactant concentration, there are not sufficient amount of water molecules to complete the hydration shell. Thus, increased number of –OH groups point towards the hydrophobic surfactant chain and tendency to form spontaneous aggregates increases rapidly with accompanied entropy gain.

2.2.1 Morphologies of Self-Assembled Aggregates

Optimal morphologies of these self-assembled aggregates can be explained through free energy minimization arguments12. Free energy of surfactant self-assembly in dilute solution can be combined by three terms:

Figure 2.1 Non-ionic surfactant, water and oil mixture self-assembles into rich variety of nanostructures10.

6 • A favorable hydrophobic contribution reflects the portion of the hydrophobic chains,

which isolate themselves within the interior of the aggregates.

• A surface term accounts for the two opposing effects. (i) Head groups coming near

each other to prevent the water – hydrocarbon tail contacts and (ii) repulsions

between head groups due to the electrostatic repulsion (for ionic surfactants),

hydration, and steric hindrance (for non-ionic surfactants).

• A geometrical packing term requires that hydrophobic region of the aggregates does

not contain either water or head groups, thus limits the geometry of the self-

assembled aggregates.

Specific aggregated geometry has unique surface and packing terms. The geometry that gives minimum free energy determines the optimal aggregate. These three terms can be interrelated into a dimensionless number, surfactant number or critical packing parameter,

is defined as =ν / 0lap c , where υ is the volume of the hydrophobic portion (hydrocarbon

chains), a0 is the optimal area of the hydrophilic group (surfactant head group), and lc is the critical chain length of the hydrophobic group (Figure 2.2). For ionic surfactants,

a0 depends on both electrolyte and surfactant concentration. The head group repulsions are screened by electrolyte concentration and head groups come near each other. Thus,

a0 decreases for ionic surfactants upon addition of electrolytes. For non-ionic surfactants, temperature rather than electrolyte concentration is controlling factor for head group interactions. Figure 2.3 illustrates the fact that surfactant numbers relate the property of surfactant molecules to the preferred curvature of the aggregates. Surfactant number, p <1/3 suggests the formation of aggregates with spherical micelles. Spherical micelles form for a single chain surfactants with a strongly polar head group such as ionic

7 surfactant in absence of electrolyte or non-ionic with larger head group. Surfactant

number, p ~1/3-1/2 and rod-like micelles are characteristic of single chain ionic

surfactants with an added electrolyte or non-ionic surfactants with intermediate head

group size. For ionic surfactants, electrolyte addition increases the surfactant number and

this leads to aggregate structures from bilayer/lamellar to reversed type structures.

Similar aggregate structure transition is observed for non-ionic surfactants but with increasing temperature instead of electrolyte concentrations. Increasing temperature

simulates effect of reducing head group size of non-ionic surfactants.

Surfactant aggregates can be considered to be built up of surfactant films. Thus, the

curvature of surfactant film7 can also be used to analyze aggregate structures.

Spontaneous curvature is considered to be positive if the surfactant film is curved

towards hydrophobic region (e.g. normal micellar structures). However, reversed

micellar structures have negative spontaneous curvature as the surfactant film is curved

towards hydrophilic region. Lamellar phase has planer surfactant film with zero

curvature. Spontaneous curvature decreases by adding second hydrophobic chain to the

surfactant molecule or by screening the head group repulsions as in the case of ionic

surfactants by adding electrolytes.

Curvature concept can be explained quantitatively by defining the mean curvature of

12 13 the surfactant film H and Gaussian curvature KG at a point on a surface as:

1 11 1 H 2 ( += ) K G = where R1 and R2 RR 21 RR 21

are the radii of curvature in two perpendicular directions at a point on surfactant film, as

14 illustrated in Figure 2.4 . A spherical aggregate forms when R1 =R2 =R

15 Figure 2.2 Illustration of surfactant packing number, =ν / 0lap c .

Figure 2.3 Surfactant packing number of surfactant molecules and corresponding optimal aggregated structure for geometrical packing reasons7.

Figure 2.4 Radii of curvature perpendicular to the surfactant film of aggregate structures14.

11 and H = R ; A cylinder forms when 1 = RR , R2 = ∞ and = 2/1 RH ; a bilayer forms when H = 0. The mean curvature and Gaussian curvature are related to the surfactant packing number as follows13: lK 2 ν 1/ Hlla +−= G 0 c 3

2.3 Sugar Based Surfactants

Sugar based surfactants such as alkyl polyglucosides, sucrose esters, sorbitan esters, and fatty acid glucamides are gaining increasing attention due to their environmentally friendly attributes such as biodegradability, non-toxicity, and less irritability to the skin.

These characteristics coupled with their synthesis from renewable resources made them excellent candidates as an alternative to the petroleum based non-ionic surfactants. Sugar surfactants are widely used in the areas of foods, cosmetics, pharmaceuticals, and detergent applications16-22.

2.3.1 Comparison of Sugar Based Surfactants to Petroleum Based

Nonionic Surfactants

Petroleum sources are limited and continuous use of these resources will lead to increased price of the petroleum based products in near future. Hydrophilic portion of petroleum based non-ionic surfactants such as alkyl polyethylene glycol ethers is primarily synthesized from ethylene oxide23. In the future, price of ethylene oxide will increase due to the decreased availability of petroleum sources and this would force the demand for alternative sources, such as surfactants from renewable resources. On the other hand, sugars like glucose, fructose, sucrose, maltose, and lactose are relatively cheaper, low toxic, plentiful and renewable starting materials for the synthesis of non-

12 ionic surfactants. Sugar surfactants are readily biodegradable24, 25 and environmentally more compatible compared to petroleum based conventional non-ionic surfactants.

Petroleum based non-ionic alkyl polyethylene glycol ether surfactants are very temperature sensitive and aqueous solutions of these surfactants turn turbid at particular temperature (cloud point) upon heating23. On the other hand, sugar based surfactants do not show this clouding phenomena and their aqueous solutions are relatively temperature insensitive. This temperature insensitivity behavior is due to the strong hydrogen bonding between the hydroxyl groups of sugar and water molecules, which prevents the considerable dehydration of the head groups at the higher temperature26, 27. This temperature insensitive behavior makes sugar based surfactants attractive for the formulation applications. Aqueous solutions of the alkyl polyethylene glycol ether surfactants are useful for the applications wherein change in emulsion types is required with increasing temperature.

2.3.2 Phase Behavior of Sugar Based Microemulsions

Phase behavior studies of non-ionic microemulsions are predominantly restricted to

28-37 water -alkane - alkyl polyethylene glycol ether (CiEj) surfactants and water - alkane –

5, 6, 38-52 alkyl polyglucosides (CmGn) surfactants . In CiEj, notation i denotes the number of carbon atoms in hydrophobic alkyl chain and j is the number of ethoxy units in the hydrophilic head group. CmGn surfactants contain m number of carbon atoms in the hydrophobic alkyl chain and n numbers of glucose groups in the hydrophilic head group.

Kahlweit et al.29, 32 discussed the general patterns of non-ionic microemulsions phase behavior based on alkyl polyethylene glycol ether surfactants. In this section, general patterns of nonionic microemulsions are reviewed and these patterns are compared with

13 reported phase behavior of sugar based microemulsions. This section also summarizes reported phase behavior studies of sugar based microemulsions in aqueous and non- aqueous systems.

2.3.2.1 General Patterns of Nonionic Microemulsions Phase Behavior

Phase behavior studies of binary mixtures provide useful information to interpret the phase behavior of ternary system of water - oil - nonionic surfactant. Figure 2.5 shows the unfolded phase prism with the phase diagrams of the three binary mixtures. Phase diagram of oil and water is the simplest of the three binary phase diagrams and oil and water mixtures are practically insoluble for the experimental temperature window of 0 to

100 °C. Oil and water binary mixture shows the upper critical point of their miscibility gap at extremely high temperature, which exists typically well above the boiling point of the oil. Increasing the temperature above the upper critical point makes oil and water mixtures soluble in each other.

Binary phase diagram of oil and nonionic surfactant shows lower miscibility gap with an upper critical point (cpα) above which nonionic surfactant is completely soluble in oil.

The upper critical temperature (Tα) also depends on the chemical nature of both the surfactant and oil. Opposing nature of these two substances (i.e. more hydrophobic oil and the more hydrophilic nonionic surfactant) shifts upper critical point at higher temperature.

The binary phase diagram of water and nonionic surfactant is the most interesting among the three binary diagrams. Water and nonionic surfactant mixture shows the upper miscibility gap with lower critical point (cpβ). Nonionic surfactant has very good

14 solubility at lower temperature and above lower critical temperature (Tα), the solubility of nonionic surfactant in water starts decreasing. This change of surfactant solubility from highly soluble in water at lower temperature to the highly soluble in oil at the higher temperature plays a key role in the understanding of the phase behavior of the ternary mixtures of water, oil and surfactant.

Figure 2.637 shows Gibb’s phase prism, which is the most convenient way to represent the detailed phase behavior studies of the ternary mixtures of water, oil and nonionic surfactant with increasing temperature. At lower temperature, surfactant primarily dissolves in the water and tie lines ascend towards the water rich phase producing surfactant rich water phase in equilibrium with the excess oil phase ( 2 ). Bar in this notation indicates that surfactant preferentially dissolves in water phase. At higher temperature, surfactant mainly dissolves in oil and tie lines ascend towards the oil rich phase producing the surfactant rich oil phase in equilibrium with the excess water phase

( 2 ). Bar indicates that surfactant mainly dissolves in oil phase. With increasing temperature, two phase region detaches from oil and surfactant binary at a temperature Tl and a critical tie line, shown as the bold line, emerges in the two phase region. Three phase region appears above this critical tie line, which is shown by the shaded triangles.

This three phase region extends with increasing temperature and disappears at the upper critical tie line at a temperature Tu. Increasing temperature above Tu, water and surfactant miscibility gap appears at temperature Tα due to the limited solubility of surfactant in water. At higher temperature, surfactant head groups becomes dehydrated and effective size of the head group decreases making the surfactant more hydrophobic

100°C

surfactant 0°C

cpβ

cpα

100°C

cmc 0°C H2O oil 0°C

100°C

Figure 2.5 Phase diagrams of three corresponding binary mixtures of the ternary mixtures of water, oil and nonionic surfactant (adapted from Kahlweit et al.)32.

Figure 2.6 Ternary phase prism of water, oil and nonionic surfactant with increasing temperature37.

17 shifting the surfactant partitioning from water phase to oil phase with increasing temperature. At higher surfactant loading, ternary mixtures do not pass through the three phase region instead they form one phase microemulsions causing the phase transition

212−− instead of following the phase sequence 232− − with increasing temperature.

Studying the phase behavior of entire phase prism requires substantial experimental work. Thus, researchers have investigated different sections passing through the phase prism such as (i) vertical sections passing through phase prism as a function of temperature (T) and surfactant concentration (γ) at constant oil to water ratio (α); (ii) vertical section passing through phase prism as a function of temperature (T) and oil to water ratio (α) at a constant surfactant concentration (γ). Figure 2.729 shows a schematic of a vertical section passing through phase prism at a constant oil to water ratio of α =

50%. At low surfactant concentration (i.e. less than the surfactant required for the formation of three phase body), two phases always exist with surfactant changing its partitioning from water to the oil phase ( 22− ) with increasing temperature. Liquid crystalline phases form at very high surfactant concentration (γ). At intermediate surfactant concentration (γ% ) and lower temperature, surfactant preferentially dissolves in water phase and the surfactant head groups become hydrated that increases the effective size of the head groups. Due to the packing of larger head groups, surfactant film is curved toward the oil phase and the mixture forms oil in water microemulsion which is in equilibrium with the excess oil phase ( 2 ). At moderate temperature ( T% ), an isotropic one phase microemulsion forms beyond surfactant concentration ( γ% ). With increasing temperature, one phase microemulsion shifts to two phase mixtures, wherein surfactant

Figure 2.7 Fish cut section through the phase prism of ternary mixtures of water, oil and nonionic surfactant containing equal masses of oil and water29.

19 preferentially dissolves in the oil phase and surfactant head groups become dehydrated which decreases the effective size of the surfactant head groups. Due to the packing of smaller head groups, surfactant film is curved towards the water phase and the mixture forms water in oil inverse microemulsion which is in equilibrium with the excess water phase ( 2).

At lower surfactant concentration, the phase sequence 212− − changes to 232−− with increasing temperature and 3 indicates that three phases - water rich, oil rich and microemulsion phase coexist at equilibrium. Phase boundaries of 232− − transition provides a shape that corresponds to the fish body and phase boundaries of 212−− transition makes a shape that relates to the fish tail. Due to the fish-like shape of the figure 2.7, section through the phase prism containing constant oil to water ratio is called a fish cut. Intersection of fish body and fish tail is defined by the point X% ( γ% , T% ) that corresponds to the minimum amount of the surfactant needed to micro-emulsify equal amount of oil and water, which is a measure of the surfactant efficiency.

2.3.2.2 Alkyl polyglucoside (APG) Surfactant Based Microemulsions

21, 22 Alkyl polyglucosides (CmGn) surfactants are gaining considerable attention due to

53 their excellent biodegradability and production from renewable sources . CmGn surfactants are widely used in cosmetics, manual dishwashing, and detergent

18, 21, 22 52, 54-60 applications . Binary phase behavior studies of CmGn surfactants indicate that CmGn surfactants are highly hydrophilic and they have limited solubility in hydrophobic oil such as alkanes. Due to their limited solubility in oils, it is difficult to prepare and study the microemulsion phase behavior of water – alkane - CmGn

20 surfactants. Cosurfactants are widely used to increase the solubility of CmGn surfactants in oils and thus, researchers have investigated phase behavior of water – alkane - CmGn - cosurfactant microemulsions41, 49-51, 61, 62.

Ryan and coworkers60 have studied the microemulsion phase behavior of water – octane – C6E2 - C10βG1 microemulsions. Figure 2.8 shows a schematic of vertical section through the phase prism at equal masses of octane and water (fish cut) with varying

C10βG1 concentration (δ). C6E2 is highly soluble in octane ( 2) and thus fish diagram exists at lower temperature for δ=0 and mixtures form two phase oil continuous emulsion with excess water at experimenatl temperature window of >20°C. With increasing

fraction of C10βG1 (i.e. δ=10, δ=25 and δ=50), solubility of surfactant mixtures in water increass as C10βG1 is mainly dissolved in water phase ( 2 ) and thus three phase body and fish diagram shifts to the higher temperature. This reported phase behaviour of quarternary mixture is very similar to that of general patterns of non-ionic surfactant

29, 32, 36 (CiEj ) microemulsions .

Ryan and coworkers52 have also investigated the intrinsic behavior of alkyl polyglucoside surfactants by studying the microemulsions formed using ternary mixtures of water- oxygenated ether oil - CmGn without using any cosurfactant. Oxygenated ether oils (CkOC2OCk, where k is the number carbon in alkyl ether chains) are relatively hydrophilic than alkanes and are better candidates to prepare CmGn based microemulsions.

Figure 2.9 shows that C9βG1 are completely soluble in C3OC2OC3 at temperatures above

50°C. Thus CmβG1 have higher solubility in CkOC2OCk than in alkanes and it is possible to study the “fish cut” phase behavior of microemulsions formed using ternary mixtures

Figure 2.8 Fish cut section through the phase prism of quarternary mixtures of water, octane, C6E2 and C10βG1 with varying C10βG1 concentration (δ) containing equal masses of octane and water60.

60 Figure 2.9 Binary phase diagram of C9βG1 and C3OC2OC3 .

23 of water –CkOC2OCk–CmβG1 with phase sequence of 232− − at desired experimental temperature window. Figure 2.10 shows the phase diagram of the ternary mixtures of water–CkOC2OCk–C8G1 as a function of temperature and surfactant composition containing equal amount of water and oil. For k=2, mixtures do not show three phase body and with increasing k from 2 to 2.1, a narrow three phase body appears. Further increasing the hydrophobicity of oil (k), shifts three phase body at higher temperature and forms larger three phase regions indicating the lower solubility of C8G1 in relatively more hydrophobic oil. Increasing k=2 to k=2.5 shifts the phase behavior at higher temperature and also increases the required surfactant concentration to form one phase microemulsions. Thus, efficiency (amount of the surfactant required to cosolubilize equal amount of oil and water) decreases with increasing k. In addition, increasing the hydrophilicity of the CmG1 surfactants by increasing sugar head group (C8G2) shifts the phase behavior to higher temperature reflecting the lower solubility of sugar groups in

52 oil . Studies suggest that phase behavior of CmGn surfactant based microemulsions containing either additional cosurfactant or relatively hydrophilic oil is very similar to that of reported non-ionic microemulsion phase behavior based on CiEj surfactants.

2.3.2.3 Sucrose Ester Surfactant Based Microemulsions

Similar to CmGn surfactants, binary phase behavior of sucrose monoalkanoate in water shows that sucrose alkanoate surfactants do not have any cloud point below 100

°C due to the strong hydrophilic nature of the sucrose head groups63, 64. Temperature insensitivity of sucrose alkanoate phase behavior is due to the strong hydrogen bonding of hydroxyl groups of sucrose head group to the water molecules. Sucrose esters are approved food additives due to their extremely mild behavior with regard to 24

Figure 2.10 Fish cut through the phase prism of the ternary mixtures of water–

52 CkOC2OCk–C8βG1 containing equal amount of water and oil .

25 dermatological properties. These properties of sucrose esters with their temperature insensitive phase behavior make them excellent emulsifier for personal care products, cosmetic applications, food industries, special detergent products, and as well as in many other applications17, 65-74.

Due to the existence of lower critical temperature (Tα) of the miscibility gap of sucrose ester – water binary at very high temperature, it is difficult to study the phase behavior of microemulsions based on water-oil-sucrose ester surfactants. Thus, researchers have reported microemulsion phase behavior of sucrose ester surfactants using cosurfactants73, 75-84. Kunieda and coworkers81 have studies the phase behavior of sucrose alkanoate based microemulsions using polyethylene glycol ether as cosurfactant.

Pes et al.83 have reported the temperature insensitive bicontinuous microemulsion phase behavior of quaternary mixtures of water-decane-sucrose monododecanoate-hexanol. In

Figure 2.11, phase transitions II-III-II (equivalent to 232− − transitions) and II-I-II

( 212−− ) have reported by varying mass fraction of hexanol to the overall surfactant concentration (W1) and overall surfactant concentration (X). Pes and coworkers found that sucrose monododecanoate is extremely hydrophilic surfactant and it is inevitable to add a cosurfactant such as medium alkyl chain alcohols to facilitate the formation of low curvature structures such as bicontinuous microemulsions (I). Study also revealed that it is possible to form temperature insensitive bicontinuous microemulsions of sucrose esters surfactants using cosurfactants.

Kabir and coworkers 64, 79 have studies the phase behavior of sucrose monododecanoate based microemulsions using different cosurfactants such as short alkyl chain alcohol (pentanol, hexanol) and long alkyl chain alcohol (heptanol, octanol,

Figure 2.11 Fish cuts through the phase prism of the quarternary mixtures of water- decane-sucrose monododecanoate-hexanol at increasing temperature progression containing equal amount of water and oil83.

27 decanol). They found that short alkyl chain alcohol tends to form bicontinuous microemulsion with phase transitions 212− − and long chain alcohols tend to form liquid crystalline phase with phase transitions 2LC2− − (where LC indicates liquid crystalline phase). Studies also suggest that phase behavior of sucrose ester surfactant based microemulsions containing cosurfactant is very similar to that of general patterns of non-ionic surfactant CiEj phase behavior.

2.3.2.4 Sugar Based Nonaqueous Microemulsions

Typically, microemulsions are isotropic and thermodynamically stable mixtures of water, oil, and surfactant. With systematically increasing oil to water ratios in these ternary mixtures, microemulsions can form microstructures ranging from water continuous micelles, bicontinuous networks to oil swollen micelles. Tendency of water molecules to form intermolecular and intramolecular hydrogen bonding network plays a key role in the formation of classical microstructures present in aqueous based microemulsions. However, studies85-97 suggest that water is not required to facilitate the self assembly of surfactants and if water is replaced with other polar solvents, which are not soluble in oil, microemulsion forms. In this section, non-aqueous microemulsions based on nonionic surfactants briefly reviewed followed by the detailed phase behavior studies reported in sugar based microemulsions.

There are several reports of formation of non-aqueous self assembly based on ionic surfactants85, 87-89, 96, 97. In general, critical micelle concentration of ionic surfactants increases in nonaqueous polar solvents than in water. In addition, liquid crystalline regions, which are present in water, either become smaller or absent in nonaqueous polar organic solvents.

28 Martino and coworkers92, 93 have studies the microemulsions in noaqueous polar solvents based on CiEj nonionic surfactants. Figure 2.12 shows the systematic phase behavior studies of quaternary mixtures of glycerol-propylene glycol-dodecane-C12E5.

With increasing mass fraction of glycerol in polar organic mixtures (y), surfactant becomes less soluble in the polar organic phase and produces the 232− − phase transition. They also reported the microemulsion phase behavior based on oil solvophobicity by increasing alkyl chain length of oils such as heptane, dodecane, and hexadecane (Figure 2.13). Higher oil solvophobicity sifts the fish diagram at higher mass fraction of glycerol (y) in the reported phase behavior. Martino and coworkers also investigated the effect of surfactant solvophobicity and solvophilicity by varying i and j in the CiEj surfactants.

Schubert et al.94, 95 have reported detailed phase behavior study of ternary mixtures of formamide (FA), octane, and CiEj surfactants. They have found that solubility of hydrocarbons in FA is slightly higher than that in water and which leads to reduced hydrophobic interaction between FA and hydrocarbon chain of surfactant molecule.

Thus, surfactant’s mutual solubility and critical micelle concentration increases upon replacing water with formamide (FA). Figure 2.14 shows the comparison of phase diagrams of the fish cuts through the phase prism of ternary mixtures of formamide- octane-C18E6 (shown by solid line) and water-octane-C12E4 (shown by dotted line).

Schubert and coworkers found that increasing the number of carbon atoms by ~5, it is possible to observe the phase transition 232− − and 212− − in the formamide-octane-

CiEj surfactant mixtures, which are similar to that are reported in aqueous microemulsions of CiEj surfactants. These nonaqueous phase behavior studies are very

Figure 2.12 Fish cut through the phase prism of the quarternary mixtures of glycerol- propylene glycol-dodecane-C12E5 with increasing mass fraction of glycerol in polar organic mixtures (y)92.

Figure 2.13 Effect of solvophobicity of oil on fish cuts through the phase prism of the quarternary mixtures of glycerol-propylene glycol-dodecane-C12E5 with increasing mass fraction of glycerol in polar organic mixtures (y)92.

Figure 2.14 Comparison of fish cuts through the phase prism of the ternary mixtures of formamide-octane-C18E6 (shown by solid line) and water-octane-C12E4 (shown by dotted line) with increasing temperature and surfactant concentration94.

32 similar to that of general patterns of nonionic microemulsion phase behavior based on

CiEj surfactants.

Sugars (sucrose, trehalose, glucose etc.) and their derivatives have multiple hydroxyl groups and they can easily form intermolecular and intramolecular hydrogen bonding networks when dissolved in different nonaqueous solvents98, 99. In addition to their polar nature, sugars’ low cost, water solubility and environmentally friendly characteristics make them ideal water replacement materials for the formulation work in food, pharmaceutical, and agricultural industries to avoid the spray drying100 and freeze drying processes. Gao and coworkers5, 6 have studies the detailed phase behavior studies of aqueous sugar based microemulsions based on alkyl polyglucoside surfactants. Figure

2.15 shows the effect of increasing sugar fraction in mixtures of aqueous sugar solutions, isobutylacrylate, C8G1 and C12G1 as surfactants, and 1,2 octanediol as cosurfactants containing equal amount of sugar and isobutylacrylate. Study revealed a large one phase microemulsion region wih incresing sugar concentrations in the aqueous phase from 70% to 80%. Gao et al. proposed a novel approach to prepare anhydrous microemulsion glasses by controlled dessication of concentrated sugar solution based microemulsions.

Figure 2.16 shows the optically clear anhydrous microemulsion glass prepared by controlled dessication approach of the 75% sugar solution based liquid microemusion sample shown by the star in Figure 2.15, which contains equal amount of sugar and isobutylacryalte oil. They have used this anhydrous microemulsion glass template for the polymerization of oil phase without the phase separation.

Gao and coworkers6 have also investigated the phase behavior of bicontinuous microemulsions of aqueous sugar solutions, divinylbenzene, C8G1 and C12G1 as

Figure 2.15 Fish cuts through the phase prism of the mixtures of aqueous sugar solutions, isobutylacrylate, C8G1 and C12G1 as surfactants, and 1,2 octanediol as cosurfactants containing equal amount of sugar and isobutylacrylate oil5.

Figure 2.16 Anhydrous microemulsion glass prepared by controlled dessication of the

75% sugar solution based microemulsions (shown by the star in Figure 2.15) containing equal amount of sugar and isobutylacrylate oil5.

35 surfactants, and 1,2 octanediol as cosurfactants containing equal amount of sugar and divinylbenzene. They have used diffusion based controlled dessication approach to prepare the anhydrous microemulsion glass templates for the polymerization of divinylbenzene phase. Using this approach, Gao and coworkerers have synthesized polydivinylbenzene membranes with 25 nm pores.

Gao et al. have used scanning electron microscopy (SEM), atomic force microscopy

(AFM), differential scanning calorimetry (DSC), and small angle netron scattering

(SANS) measurement techniques to characterize anhydrous sugar based microemulsion glasses before and after the polymerization of the oil phase. Figure 2.17 shows the glass transition measurements of the anhydrous microemulsion glasses prepared by controlled dessication of the 75 wt% sugar solution based liquid microemulsions containing 50 wt% to 80 wt% divinylbenzene oil loading (α) using Modulated Differential Scanning

Calorimetry (MDSC) technique. Glass transition temperatures decreases from 75 °C to

64 °C with increasing oil loading from 50 wt% to 80 wt%. This decrese in glass transition temperature (Tg) is consistent with the decrease in Tg of the liquids confined in the porous silica glasses101. Gao and coworkers have characterized these anhydrous microemulsion glasses, prepared by controlled dessication of liquid microemulsions, before and after polymerization using small angle neutron scattering (SANS) measurement technique (Figure 2.18). Except oil loading of 70 wt%, neutron scattering data shows the progressive increase in scattering at low q which indicates the probable phase separation during the controlled dessicaion of the liquid microemulsions. However, at higher oil loading, neutron scattering data of dessicated microemulsion glass becomes comparable to that of classical aqueous microemulsions. Analysis of these neutron

Figure 2.17 Modulated differential scanning calorimetry (MDSC) measurements of the microemulsion glasses prepared by controlled desiccation of liquid microemulsions prepared from a 75% sugar solution with divinylbenzene mass loading (α) varies from 50 wt% to 80 wt% at constant surfactant concentration (γ) of 22.5 wt%6.

Figure 2.18 Small angle neutron scattering (SANS) measurements of the sugar based microemulsion glasses before and after polymerization of divinlbenzene oil.

Microemulsion glasses were prepared by controlled desiccation of liquid microemulsions prepared from a 75% sugar solution with divinylbenzene mass loading (α) varies from 50 wt% to 70 wt% at constant surfactant concentration (γ) of 22.5 wt%6.

38 scattering data at 70 wt% oil loading using classical Teubner Strey model102, which is typically used for aqueous microemulsions, yields domain sizes 8.6 and 8.3 nm before and after polymerization.

Proposed diffusiion based controlled dessication approach to create anhydrous microemulsion glasses by Gao and coworkers5, 6 simulates the spray drying phenomena and has limited practical applications while handling the large quantities of auqeous based sugar microemulsions. Thus, in chapter 5, we have presented a novel direct mixing approach to form the anhydrous molten microemulsion glasses and these molten glasses are easily extrudable for variety of applications. These molten glasses solidify and crack into pieces upon cooling below their glass transition temperature. They are optically clear and contains more than 50 vol% of oil. Small angle neutron scattering (SANS) measurement of microemulsion glasses prepared by direct mixing approach provides neutron scattering data that is typical of aqoueous microemulsions and overcomes the limitation of controlled dessication approach which is presented by Gao et al5, 6.

39 Chapter 3 Experimental Section

3.1 Introduction

This chapter provides detailed description of materials (Table 3-1), experimental methods, and characterization techniques used for the investigation of sugar based aqueous and non-aqueous microemulsions. This section also describes the sample preparation procedures and characterization techniques that are used to study the phase behavior of sugar based microemulsions.

3.2 Sugar Based Aqueous Microemulsions

3.2.1 Materials

Food grade sucrose laurate (80% monolaurate, 20% higher substitution) and sucrose oleate (74% sucrose monooleate, 23% sucrose dioleate, 3% higher substitution) surfactants were supplied by Mitsubishi Kagaku-Foods Corporation, Japan and used as received. Technical grade C8G1 and C12G1 were supplied by Henkel (APG 225 and APG

600, respectively) in the form of 65 and 50 wt % solutions in water respectively and used as received.

D-limonene (97%) with 0.1 wt% butylated hydroxytoluene (BHT) added as an antioxidant was purchased from Aldrich Chemical and used as received. Sucrose and trehalose dihydrate (99%) were purchased from Acros Organics and used as received.

Deionized water with a specific resistance of 18.2 MΩ cm was used in preparing all samples.

40 Table 3-1 Molecular weights and densities of chemicals used

Materials Molecular weight (g/mol) Density (g/ml)

Sucrose 342.29 1.587

Trehalose dihydrate 378.29 ca. 1.5

Limonene 136.24 0.843

Sucrose laurate 524.60 ca. 1.5

Sucrose Oleate 606.74 ca. 1.5

Sucrose caprylate 468.49 1.5

41 3.2.2 Phase Diagram Determination

Following the nomenclature of Kahlweit and Strey32, 36, composition variables used in determining the phase diagrams are defined as follows. Mass ratio of oil to sugars in the

mixture (α):

oil α = ×100 in wt% (1) (oil + sugars) mass ratio of long chain surfactant to the short chain surfactant (ε) for sucrose esters based microemulsions and alkyl polyglucoside based microemulsions respectively:

oleate sucrose oleate ε = ×100 in wt % (2) oleate (sucrose oleate + sucrose lurate)

CG ε =12 1 ×100 in wt % (3) (C12 G 1+ C 8 G 1 )

and mass fraction of surfactant in the overall mixture (γ).

3.2.2.1 Microemulsion Sample Preparation

Stock solutions of 25 wt% sucrose oleate and 40 wt% sucrose laurate in 65 wt% sugar were prepared to facilitate the phase behavior studies. One gram samples were prepared by gently heating mixtures of sugar, surfactant solution, and water in flat bottom screw- cap tubes, evaporating excess water when necessary by passing argon over the sample, then adding d-limonene. Complete dissolution of the sugars is important to avoid crystallization. The sample tubes were immersed in isothermal water baths (±0.02 °C), stirred vigorously with gold-coated NdFeB magnetic stir-bars, and then allowed to phase

42 separate for up to 12 hours to locate accurately boundaries between one and two phase regions. The presence of multiple phases was determined by visual inspection in both transmitted and scattered light, using crossed polarizers to determine the presence of liquid crystalline phases. Although optical rotation arising from the optically pure sugars can be observed, this is weak and noticeably distinct from that arising due to liquid crystalline phases.

3.2.3 Neutron Scattering

Neutron scattering experiments were performed using the 30-m small angle neutron scattering (NG-3 SANS) instrument at the National Institute of Standards and

Technology (NIST), Gaithersburg, MD. Neutrons of wavelength λ = 6 Å were collimated and focused on samples held in 1 mm quartz cells. The coherent scattering, arising principally from the difference in mass density between the sugar and oil, was sufficient compared to the incoherent scattering background even without deuteration.

Three sample-to-detector distances (1.33, 4.5 and 13.17 m) were used to cover a scattering vector q (4π sin(θ /2)/λ)) range of 0.015 to 6 nm-1. Additional neutron scattering experiments were performed using the small angle neutron diffractometer

(SAND) instrument at the Argonne National Laboratory (ANL), Argonne, IL. Data were corrected for background, circularly averaged, then set to an absolute intensity scale using software provided by NIST and ANL.

SANS and SAND data were fitted using the Teubner and Strey model102 for the static scattering indensity distribution I(q) of microemulsions:

/)8( Δρφφξπ 2 c TS 21 2 (4) qI )( = 2 4 + b 12 ++ 2 qcqca

43 where a2, c1 and c2 are variables related to the Landau free energy expansion. φ1 and φ2 represent the volume fraction of the oil and water phase respectively and Δρ corresponds to the scattering length difference. ξTS is the correlation length and b accounts for the incoherent background, which results due to the scattering from hydrogen. In practice,

2 95, 103, 104 the factor (8π/ξTS)φ1φ2Δρ c2 is incorporated into the parameters a2, c1 and c2 and scattering data is least-squares fitted to

1 (5) qI )( = 2 4 + b 12 ++ 2 qcqca

This scattering intensity equation is equivalent to the real-space density correlation function:

d TS −r/ξ ⎡2πr ⎤ G(r) = e TS sin⎢ ⎥ (6) 2πr ⎣ d TS ⎦ representing a periodic structure modulated by an exponential decay. The parameters dTS and ξTS , representing the domain size (periodicity) and correlation length respectively are related to the scattering parameters via

1 − ⎡ 1 ⎤ 2 1 ⎛ a ⎞ 2 1 c d = 2π⎢ ⎜ 2 ⎟ − 1 ⎥ (7) TS ⎢ ⎜ ⎟ ⎥ 2 ⎝ c2 ⎠ 4 c2 ⎣⎢ ⎦⎥

1 − ⎡ 1 ⎤ 2 1 ⎛ a ⎞ 2 1 c ξ = ⎢ ⎜ 2 ⎟ + 1 ⎥ (8) TS ⎢ ⎜ ⎟ ⎥ 2 ⎝ c2 ⎠ 4 c2 ⎣⎢ ⎦⎥

44 3.3 Sugar Based Non-aqueous Microemulsions

3.3.1 Materials

Sucrose caprylate and sucrose oleate surfactants were supplied by Mitsubishi

Kagaku-Foods Corporation, Japan and used as received. D-limonene (97%) with 0.1 wt% butylated hydroxytoluene (BHT) added as an antioxidant was purchased from

Aldrich Chemical and used as received. Sucrose and trehalose dihydrate (99%) were purchased from Acros Organics and used as received. Deionized water with a specific resistance of 18.2 MΩ cm was used in preparing all samples.

3.3.2 Phase Diagram Determination

Following the nomenclature of Kahlweit and Strey32, 36 composition variables used in determining the phase diagrams are defined as follows. Mass ratio of oil to sugars in the mixture (α):

oil α = ×100 in wt% (9) (oil + sugars) mass ratio of long chain surfactant to the short chain surfactant (ε)

sucrose oleate ε =×100 in wt % (10) (sucrose oleate+ sucrose caprylate) and mass fraction of surfactant in the overall mixture (γ)

3.3.2.1 Microemulsion Glass Sample Preparation

Samples were prepared by gently heating mixtures of sugar, surfactant solutions, and water in flat bottom screw-cap tubes, evaporating excess water by passing argon over the sample followed by vacuum drying. Complete dissolution and accurate dehydration of

45 the sugar/surfactant solutions is critical. Prior to dehydration, samples were pre-weighed to an accuracy of ±0.1 mg. Initial dehydration with dry argon gas at room temperature was performed with continuous rotation of the tubes to form thin viscous films of 90 to

92 wt% sugar/surfactant. The sample tubes were subsequently transferred to a vacuum oven and ramped carefully to 60°C over ~4 hours to maximize drying area through controlled foaming of the sugar/surfactant films. The sample tubes were weighed periodically and dehydration was terminated when the sugar/surfactant mixtures reached

99.5 wt%. Drying times of 2 and 6 days are typical of one and five gram samples respectively.

After addition of d-limonene, the sugar/surfactant powders were dispersed at room temperature using NdFeB stir-bars at room temperature, then thermostated at

365.00±0.02 with no further stirring. For samples containing α≤20% oil, there is insufficient oil to disperse the sugar/surfactant powders at room temperature. Samples are thus heated and stirred at 400 K for two minutes to mix the molten sugar/surfactant powder with limonene, then thermostated at 365 K for observation. Thermostated samples are observed for one hour, although one-phase samples generally become optically transparent within 5 minutes. The presence of multiple phases was determined by visual inspection in both transmitted and scattered light, using crossed polarizers to check for the presence of liquid crystalline phases. The water content of one-phase microemulsion glasses, containing limonene, was validated by Karl Fischer titration, yielding water content of 0.5 to 1 wt% on an oil-free basis and corresponding closely to the 99.5 wt% sugar/surfactant concentration expected following the dehydration procedure.

46 3.3.3 Neutron Scattering

Neutron scattering spectra were acquired using the Small Angle Neutron

Diffractometer (SAND) instrument at Argonne National Laboratory, using the instrument software for background correction and circular averaging. Even without deuteration, we found that the coherent scattering, arising from the difference in mass density between the sugar and oil, was sufficiently large compared to the incoherent scattering background.

SANS spectra were analyzed using the Teubner and Strey model102 for the scattering I(q) from bicontinuous microemulsions:

1 (11) qI )( = 2 4 + b 12 ++ 2 qcqca

In this model, a2, c1 and c2 are variables related to the Landau free energy expansion and b is the incoherent background. The physical parameters dTS and ξTS , representing the domain size (periodicity) and correlation length present in the microemulsions, respectively are calculated from the fitted parameters through:

1 − ⎡ 1 ⎤ 2 1 ⎛ a ⎞ 2 1 c d = 2π⎢ ⎜ 2 ⎟ − 1 ⎥ (12) TS ⎢ ⎜ ⎟ ⎥ 2 ⎝ c2 ⎠ 4 c2 ⎣⎢ ⎦⎥

1 − ⎡ 1 ⎤ 2 1 ⎛ a ⎞ 2 1 c ξ = ⎢ ⎜ 2 ⎟ + 1 ⎥ (13) TS ⎢ ⎜ ⎟ ⎥ 2 ⎝ c2 ⎠ 4 c2 ⎣⎢ ⎦⎥

47 3.3.4 Modulated Differential Scanning Calorimetry (MDSC)

MDSC measurements were performed using a TA Instruments Q100 calorimeter

(New Castle, DE) with modulation amplitude, time, and heating rate set to ±1°C, 60 seconds and 2°C/min, respectively. N2 purge flow was set to 50 ml/min. Samples were sealed in aluminum pans during the measurements. Reversible heat capacity of microemulsion glasses was plotted against temperature to determine the midpoint heating glass transition temperatures.

3.3.5 Rheometry

A TA Instruments AR-2000 (New Castle, DE) controlled stress rheometer equipped with a high pressure cell was used for the rheological measurements. Although the cell is capable of being pressurized to 2000 psi, these experiments were completed at ambient pressure inside the sealed chamber in the temperature range of 335 to 365 K. Frequency sweeps were completed at a strain of 0.005, which was determined to be in the linear viscoelastic regime by amplitude sweeps.

3.3.6 Magnetic Resonance Imaging

MRI images and self-diffusion coefficients were obtained using a Bruker Biospec

70/30 MRI scanner (Billerica, MA) equipped with a 7 Tesla magnet and 400 mT/m field gradients. Samples comprising of seven glass tubes containing different microemulsion glasses were positioned in the center of the RF coil (72 mm diameter). Scout images using multi-slice multi-echo were acquired to select regions for self-diffusion coefficient measurements that avoided cracks present in the samples. Self-diffusion coefficient

48 measurements were performed using Bruker’s standard spin echo diffusion sequence

(FOV 6 x 6 cm2, data matrix 128 x 64, TR/TE = 2000/60 ms, slice thickness = 5 mm, gradient duration (δ) = 10 ms, time delay (Δ) = 40 ms, NEX= 1) with diffusion gradient strengths set to 0, 6, 12, 24, 48, 60, 72, and 84 mT/m.

3.3.7 Scanning Electron Microscopy

To visualize the microstructure of bicontinuous microemulsion glasses, which are solid at room temperature, samples were vacuum dried to vaporize the oil trapped in their interstices. Vacuum dried samples were sputter coated with 1-2 nm Pt and then imaged at room temperature using a scanning electron microscope (SEM, Hitachi S-900) at 2 kV accelerating voltage.

49 Chapter 4 Sugar Based Aqueous Microemulsions

4.1 Summary

We have studied the phase behavior and microstructure of edible microemulsions of d-limonene with concentrated sugar solutions (>65 wt%) using either mixtures of sucrose esters (sucrose laurate and sucrose oleate) or mixtures of alkyl polyglucosides

(C8G1 and C12G1) as surfactants. The phase behavior of these mixtures is systematically studied as a function of temperature and surfactant composition, identifying the specific effects of sugar concentration, surfactant chain length, and oil loading on the formation of microemulsion and lamellar phases. Small-angle neutron scattering experiments confirm the presence of well-structured microemulsions with domain sizes ranging from ~35 to

60 nm. With few exceptions, the patterns of microemulsion phase behavior with concentrated sugar solutions are very similar to that of aqueous systems.

4.2 Introduction

Microemulsions, comprising of surfactant, oil, and water, have widespread utility in detergency, synthesis of nanoparticles, drug delivery, microreactors, and other applications that take advantage of their self-assembled microstructure and thermodynamic stability. Furthering this range of applications, our recent report of anhydrous microemulsion glasses demonstrated that sugar-rich microemulsions, containing equal masses of polymerizable liquid oils and sugars, can be completely dehydrated to the solid glassy state without phase separation5.

The formation of microemulsion glasses starts from liquid precursor microemulsions wherein water in traditional microemulsions is replaced with concentrated (>65 wt%)

50 sugar solutions. We report here the detailed phase behavior and structure of sugar-based microemulsion glass precursors prepared using edible surfactants (sucrose oleate/sucrose laurate) and d-limonene, the principal component of citrus oil. Using supersaturated, equimolar solutions of sucrose and trehalose as the “aqueous” phase, we studied the effects of varying sugar concentration, alkyl chain length of the surfactant, oil loading, and increasing surfactant concentration on the phase behavior. Neutron scattering spectra, as analyzed using the Teubner-Strey model was used to probe the domain size and correlation lengths of the microemulsion structure. The wide temperature stability of these concentrated sugar microemulsions (~20 to 65°C) achievable with as little as ~7 wt% surfactant, are important characteristics that make them useful not only for the preparation of solid microemulsion glasses by spray drying, but also in various surface cleaning applications.

4.3 Results

4.3.1 Effects of Increasing Sugar Concentration

Figure 4.1 and Figure 4.2 show the phase diagram of sugar-based-microemulsions containing equal masses of sugar and d-limonene (α=50%). Water used in traditional microemulsions is replaced with supersaturated 65, 75 and 80 wt% aqueous solutions of sugar. Phase boundaries delineate two phase emulsion, one phase microemulsion, and one phase liquid crystalline regions. With increasing sugar concentration in the aqueous phase, the one phase regions shifts progressively downward. With the sucrose

51 80 65% sugar; ε=70%; α=50% 75% sugar; ε=70%; α=50%

2Φ 60 C) 1Φ Ο e ( 50 emperatur

T 40 1Φ lamellar 30 2Φ 1Φ

20 0.05 0.06 0.07 0.08 0.09 0.10 0.11 0.12 Overall Surfactant Mass Fraction

Figure 4.1 Phase diagram of aqueous mixtures of sugar, limonene, sugar ester surfactants showing the progression of phase behavior with increasing sugar concentration.

Markings identify temperature and composition of microemulsion and liquid crystalline samples probed with SANS (Figure 4.3).

52 75% sugar; ε=50%; α=50% 90 80% sugar; ε=50%; α=50% 2Φ 80

70 C) Ο 60 1Φ

50 1Φ lamellar Temperature ( 40

30 2Φ

20 0.07 0.08 0.09 0.10 Overall Surfactant Mass Fraction

Figure 4.2 Phase diagram of aqueous mixtures of sugar, limonene, sugar ester surfactants showing the progression of phase behavior with further increase in sugar concentration.

Not shown is a small one phase lamellar region present above 9% surfactant for 80% sugar.

53 oleate:sucrose laurate ratio (ε) fixed at 70:30, increasing the sugar concentration from

65% to 75%, causes the upper phase boundary to shift 30°C downwards (Figure 4.1).

The lamellar phase and the lower bound, which presumably also exist for 75% sugar, are shifted to below room temperature. However, the samples phase separate very slowly at room temperature, precluding accurate determination of phase boundaries below room temperature.

The same phenomena are observed for sucrose oleate:sucrose laurate ratio (ε) fixed at

50:50 (Figure 4.2). In this case, both the upper and lower boundaries shifts downwards in temperature as the sugar concentration increased from 75 to 80%. Microemulsions with

80% sugar in their aqueous phase are viscous and require several hours to phase separate.

Representative microstructures of the microemulsion and lamellar regions was determined using SANS for the 65% sugar sample at temperatures and surfactant loading indicated in Figure 4.1. SANS spectra of the microemulsion (Figure 4.3), corresponding to composition marked by stars in Figure 4.1, is dominated by a single peak, analysis of which yields Teubner-Strey domain size95, 102-104 and correlation length of 44.8 and 21.7 nm, respectively. SANS spectra of the liquid crystalline phase (Figure 4.3) show two peaks consistent with a lamellar structure with repeat spacing of ~28 nm.

4.3.2 Effects of Surfactant Alkyl Chain Length

4.3.2.1 Sucrose Ester Surfactants

Fixing the mass ratio of sugar to d-limonene at 50:50 and concentration of sugar in the aqueous phase at 75%, increasing the fraction of the longer chain sucrose oleate surfactant from ε=50 to 70% shifts the one phase region downwards (Figure 4.4). The

54 γ=0.12; ε=70%; d =55.43 nm; d =27.96 nm; T=25 oC 60 1 2 o γ=0.12; ε=70%; d=44.82 nm; ξTS=21.7 nm; T=60 C

40 ) -1 30 I (cm

0 0.005 0.010 0.015 0.020 0.025 0.030

q (Å-1)

Figure 4.3 SANS spectra of microemulsion and lamellar phase samples marked in Figure

1. Solid line fitted to the microemulsion SANS spectra is calculated from the Teubner-

Strey model. SANS measurements performed at NIST.

55 75% sugar; ε=50%; α=50% 75% sugar; ε=60%; α=50% 90 75% sugar; ε=70%; α=50% 2Φ 80

70 1Φ C) O 60

Temperature ( 1Φ 1Φ lamellar 40

30 2Φ 1Φ 20 0.06 0.07 0.08 0.09 0.10 Overall Surfactant Mass Fraction (γ)

Figure 4.4 Phase diagram of aqueous mixtures of sugar, limonene, sugar ester surfactants showing the progression of phase behavior with varying ratio of sucrose oleate and sucrose laurate surfactants.

56 upper phase boundary shifts downwards by ~25°C, for every 10% increase in the sucrose oleate fraction. Accompanying this downwards shift with increasing size of the effective surfactant alkyl chain length is an enlargement of the liquid crystalline phase, consistent with interfacial curvature arguments27, 105 and the general patterns of microemulsion phase behavior observed for alkyl glucoside surfactants42, 106.

4.3.2.2 Alkyl Polyglucoside Surfactants

Fixing the mass ratio of sugar to d-limonene at 50:50 and concentration of sugar in the aqueous phase at 75%, increasing the fraction of the longer chain C12G1 surfactant from ε=85 to 95% shifts the one phase region downwards (Figure 4.5). The upper phase boundary shifts downwards by ~10°C, for every 5% increase in the C12G1 fraction.

Accompanying this downwards shift with increasing size of the effective surfactant alkyl chain length is an enlargement of the liquid crystalline phase, consistent with interfacial curvature arguments27, 105 and the general patterns of microemulsion phase behavior observed for alkyl glucoside surfactants42, 106.

4.3.3 Compensatory Effects of Sugar Concentration and Surfactant

Alkyl Chain Length

The opposing effects of increasing sugar concentration and sucrose laurate fraction on temperature of the one phase microemulsion window (Figures 4.1, 4.2 and 4.4) can be used to advantage in forming one phase microemulsions at specific temperatures for arbitrary sugar concentrations. Should it be desirable to have a one phase microemulsions containing equal masses of sugar and d-limonene at ~50°C, Figure 4.6

57 75% sugar; ε=90%; α=50% 75% sugar; ε=95%; α=50% 90 75% sugar; ε=85%; α=50%

80 2Φ

70 C)

o 60 1Φ

50 1Φ lamellar 40

Temperature ( 2Φ 30

10 0.03 0.04 0.05 0.06 0.07 0.08 0.09 Overall Surfactant Mass Fraction (γ)

Figure 4.5 Phase diagram of aqueous mixtures of sugar, limonene, alkyl polyglucoside surfactants showing the progression of phase behavior with varying ratio of C8G1 and

C12G1 surfactants.

75% sugar; ε=50%; α=50% 90 70% sugar; ε=60%; α=50% 65% sugar; ε=70%; α=50%

80 2Φ

1Φ 1Φ 60

Temperature (C) 40 1Φ

1Φ lamellar 30

20 0.05 0.06 0.07 0.08 0.09 0.10 Overall Surfactant Mass Fraction

Figure 4.6 Phase diagram of aqueous mixtures of sugar, limonene, sugar ester surfactants showing the compensatory adjustment of long to short chain surfactant ratio to accommodate different sugar concentrations.

59 shows how the sucrose oleate:sucrose laurate ratio can be varied to compensate for varying sugar concentrations and maintain one phase conditions.

4.3.4 Effects of Varying Oil Loading

Figure 4.7 shows the effects of reducing oil loading from 50:50 limonene:sugar to

30:70 limonene:sugar, while the sucrose oleate:sucrose laurate ratio is fixed at 50:50 with

75% sugar in the aqueous phase. Reducing the oil loading from α=50% to 30% shifts the one phase region downwards and causes significant expansion of the liquid crystalline region to lower surfactant concentration. Again, the high viscosity of the samples precluded determination of the lower liquid crystalline and microemulsion boundaries.

These boundaries are nonetheless evident when the phase behavior is shifted upwards by reducing the sucrose oleate:sucrose laurate ratio to 40:60 (Figure 4.8). Reducing the oil loading also reduces the minimum amount of surfactant necessary to form one phase microemulsions from ~7 wt% to less than 5 wt%.

4.3.5 Effects of Increasing Surfactant Concentration On

Microemulsion Structure

Fixing the mass ratios of sucrose oleate:sucrose laurate and sugar:oil at 50%, we studied the structure of microemulsions with increasing surfactant concentrations, marked in Figure 4.9, using SANS. The SANS spectra and model lines from Teubner–Strey analysis is shown in Figure 4.10. With increasing concentration of surfactant, the domain size shrinks monotonically with increasing surfactant concentration consistent with the packing of a larger interfacial area in a fixed volume (Figure 4.11).

60 90 75% sugar; ε=50%; α=50% 75% sugar; ε=50%; α=30% 80 2Φ

50 Temperature (C) 40 1Φ 1Φ lamellar

20 0.06 0.07 0.08 0.09 0.10 Overall Surfactant Mass Fraction

Figure 4.7 Phase diagram of aqueous mixtures of sugar, limonene, sugar ester surfactants showing the progression of phase behavior with varying oil loading. Very slow phase separation precluded precise determination of lower boundaries for the lamellar and microemulsion phases at 30% oil loading.

75% sugar; ε=40%; α=30% 80 75% sugar; ε=50%; α=30%

2Φ 70

Temperature (C) 40 1Φ

1Φ lamellar 30

20 0.05 0.06 0.07 0.08 0.09 0.10

Overall Surfactant Mass Fraction

Figure 4.8 Adjusting the sucrose oleate:sucrose laurate ratio for 30% oil loading from

50:50 to 40:60 shifts the microemulsion and lamellar regions upwards, allowing for precise determination of lower phase boundaries.

90 75% sugar; ε=50%;α=50%

2Φ 80

70 1Φ

50 1Φ lamellar Temperature (C) 40 2Φ

0.07 0.08 0.09 0.10 0.11 0.12 0.13 0.14 Overall Surfactant Mass Fraction

Figure 4.9 Phase diagram and composition-temperature of microemulsions samples probed with SANS (Figure 4.10).

γ = 0.09; ε=50%; d=60.4 nm; ξ = 25.9 nm; T=60 oC TS o γ = 0.1; ε=50%; d=52.5 nm; ξTS = 25.5 nm; T=60 C 250 o γ = 0.12; ε=50%; d=45.5 nm; ξTS = 15.5 nm; T=60 C o γ = 0.13; ε=50%; d=39.9 nm; ξTS = 17.3 nm; T=60 C γ = 0.14; ε=50%; d=36.6 nm; ξ = 16.4 nm; T=60 oC 200 TS

150 ) 1 -

I (c 100

0 0.005 0.010 0.015 0.020 0.025 0.030

q (Å-1)

Figure 4.10 SANS spectra of concentrated sugars, d-limonene and surfactant mixtures

(Figure 8) showing the effect of increasing surfactant concentration. Symbols and lines represent measured and model calculated intensities, respectively.

75% sugar; ε=50%; α = 50%; T=60 0C (NIST) 0 75% sugar; ε=50%; α = 50%; T=60 C (ANL) 60

d (nm)

30 0.08 0.09 0.10 0.11 0.12 0.13 0.14 0.15 Overall Surfactant Mass Fraction

Figure 4.11 Variation of domain size with increasing surfactant concentration.

65 4.4 Discussion

A striking observation from this study is the large one phase microemulsion and one phase lamellar regions present in the phase diagram of sugar-rich d-limonene microemulsions of either sucrose esters (sucrose laurate and sucrose oleate) or of alkyl polyglucosides (C8G1 and C12G1). In all the phase diagrams, a two-phase coexistence region between the one phase microemulsion and one phase liquid crystalline regions is expected because of differences in their internal symmetry107 and order parameter.

However, despite a concerted effort to locate these two phase regions, none were observed. These two phase regions likely span only a very small temperature window (<

0.2°C) and/or the refractive index difference between the microemulsion and lamellar phases is too small to observe the two phases. Consistent with earlier observations in predominantly aqueous systems with alkyl glucoside surfactants26, 39, 42, 51, 52, 106, 108, 109, the one phase region of these sugar-based microemulsions also spans a much larger temperature window than that typically observed for non-ionic oligoethyleneglycol surfactants36, 110, 111. Figure 4.9 shows, for example, mixtures containing equal amounts of sugar and d-limonene with only 10 wt% surfactant that can be heated from room temperature to 80°C with no phase separation. For samples containing more surfactant, no visible change in optical transparency can be observed upon heating from the one phase microemulsion state at room temperature, across the one phase lamellar region, and up to the upper phase boundary at >80°C.

In practical spray drying processes, the complex interplay of water and oil evaporation during drying of these liquid microemulsion glass precursors lead to compositional gradients that become trapped in the sample. Controlled dehydration of

66 these microemulsions in thermostated desiccant filled chambers whose vapor phase is saturated with limonene oil does lead to solid transparent microemulsion glasses.

However, gradients set into the samples during desiccation lead to inconsistent compositional, physical, and microstructural analysis. To minimize compositional gradients and other drying derived artifacts, we are developing techniques for handling and studying the phase behavior of “ultra-viscous” microemulsion that form at much higher sugar concentrations (>95%).

4.5 Conclusions

We have mapped out the phase diagrams of edible microemulsions of concentrated sugar solutions with d-limonene. The surfactants used, sucrose laurate and sucrose laurate, are very efficient and allow the preparation microemulsions containing equal masses of limonene and sugar at overall surfactants concentrations less than 10 wt%. Increasing concentration of sugar in the supersaturated aqueous phases, simulating the effect of dehydration, e.g., in a spray-dryer, shifts the one phase region downwards. Nonetheless, the temperature range of one phase microemulsions can be tuned effectively by variation of the ratio of long and short chain sucrose ester surfactants. Reduction of oil loading shifts the temperature of the microemulsion region downwards. This is accompanied by a reduction in the minimum amount of surfactant necessary to form single phase microemulsions and an enlargement of an adjacent single phase lamellar phase. Two phase regions, which typically separate single phase microemulsion and lamellar regions were very small and never observed. Small angle neutron scattering confirms the presence of microstructure with domain sizes that decrease in size with increasing surfactant loading.

67 Chapter 5 Sugar Based Non-aqueous Microemulsions

5.1 Summary

In this study, we explored the self assembly of sucrose ester surfactants (sucrose oleate/sucrose caprylate) in anhydrous sugars (equimolar sucrose/trehalose) and oil

(limonene) mixtures. Our study reveals that anhydrous powders of sugars and surfactants suspended in oil can spontaneously form molten glasses with nanometer size domains of sugar and liquid oil without mixing. The optical clarity and solid appearance of these glasses at room temperature belie their inclusion of more than 50 vol% oil, which retain liquid-like diffusivities. The unique combination of solid- and liquid-like properties may lead to broad applications in encapsulation, template synthesis, sensors and optical devices.

5.2 Introduction

In aqueous systems, the hydrophobic effect drives the self-assembly of amphiphiles into a broad range of micellar, rod-like, bicontinuous, and liquid-crystalline complex fluids, which have myriad biological, materials, and product applications. Amphiphilic self-assembly is not limited to aqueous systems, however. Replacement of water with supercritical carbon dioxide, for example, results in complex fluids that combine the best properties of gases and liquids112. Along this vein, we explored the self-assembly of surfactants in anhydrous sugars, where the low-cost, water-solubility, low toxicity, and stabilizing properties of glassy sugars make them ideal water-replacements for many pharmaceutical, food, and materials synthesis applications.

68 We report here the detailed phase behavior and microstructure of sugar based microemulsion glasses prepared using edible surfactants (sucrose oleate/sucrose caprylate) and d-limonene, the principal component of citrus oil. We have replaced water in traditional microemulsion with anhydrous powder of sugars (equimolar sucrose/trehalose) to prepare the solid microemulsion glasses. The spontaneous mixing of molten sugars and oil to the nanometer scale, as demonstrated here using food-grade surfactants, sugars, and limonene oil, has broad consumer product applications, potentially replacing many spray and freeze drying processes with direct melt extrusion.

Complex glasses may also be used as templates for nanomaterial synthesis by replacing the limonene oil with polymerizable monomers, e.g., tetrafluoroethyelene, or by non- aqueous sol-gel chemistries113-115 to permit complementary templating of the sugar glass structure, which can be removed subsequently by simple immersion in excess water. For applications where water solubility is undesirable, the sugar skeleton can be stabilized by reaction with multifunctional isocynates to form urethane crosslinks. Broader applications of these complex glasses include sensor and optical applications where the clarity of the solid glasses may be coupled with the rapid response of molecularly mobile organic liquids.

5.3 Results and Discussion

5.3.1 Spontaneous Formation of Anhydrous Microemulsion Glasses

The spontaneous solubilization of sugars (equimolar sucrose/trehalose) and oil

(limonene) by surfactants (sucrose oleate/sucrose caprylate), as shown in Figure 5.1, bears much similarity to the surfactant-driven spontaneous microemulsification of water

~52 vol% liquid oil with a Mohs hardness of 0.7.

70 and oil mixtures32. However, upon cooling below their glass transition temperature

(~330 K), molten glasses, solidify and crack into pieces. The hardness (0.7 mohs) and optical clarity of these glasses are remarkable considering that they contain ~52 vol% liquid oil. Although a lower temperature bound for these one-phase microemulsion glasses is certain to be present, phase separation has not been observed for samples cycled between molten and solid states or slowly cooled through the glass transition in thermostated water baths. Dynamically arrested microemulsion glasses kept for over six months at room temperature also show no signs of phase separation or crystallization.

5.3.2 Phase Behavior of Anhydrous Microemulsion Glasses

In the molten state at 365 K, the phase behavior of sugar-oil microemulsions closely parallels that observed for water-oil mixtures (Figure 5.2). For equal mass loadings of oil and sugar, the one-phase region (Figure 5.2a) is bounded by upper and lower limits in the mass ratio of long chain to short chain surfactants (ε). At fixed overall surfactant mass loading (γ) of 20 wt% (Figure 5.2b), a continuous one-phase channel extends from the sugar-surfactant binary to ~60 wt% oil loading on a surfactant-free basis (α), beyond which solid microemulsion glasses do not form. The extreme viscosity of the sugar-oil mixtures precludes assignment of the multiphase regions bounding the one-phase regions into two-phase and three-phase regions typically observed in aqueous systems36.

Nonetheless, the interfacial curvature, as set by the ratio of long-chain to short-chain surfactants27, remains the deterministic variable controlling microemulsification of sugar- oil mixtures in the molten glass state.

Equimolar mixture of sucrose and trehalose is helpful to prevent the crystallization of individual sugar molecules in the prepared microemulsion glasses. However, we have

71 a b

Figure 5.2 Phase diagrams for molten sugar – limonene microemulsion glasses at 365 K.

Multiple phases are present above and below the boundaries delineating the one phase

(1φ) microemulsion region. (a) Phase diagram for 50:50 limonene oil to sugar mass ratio

corresponding to α=50%. Letter symbols correspond to compositions probed by small

angle neutron scattering (Figure 5.3) and magnetic resonance imaging (Figure 5.4). (b)

Phase diagram at fixed overall surfactant loading of γ=20%. Square symbols for phase

boundaries at low oil loadings (α≤0.3) were estimated from samples prepared heated

briefly to 400 K then observed at 365 K. Room temperature self-diffusion coefficients of

limonene oil present in the interstices of the microemulsion glasses measured by MRI

(Figure 5.4) are shown for compositions marked by stars. For comparison, the self-

diffusion coefficient of pure limonene measured under identical conditions was 1.3×10-5

cm2/s.

72 found that there is no sign of crystallization inside these microemulsion glasses up to sucrose:trehalose ratios of 40:60 or 60:40 volume basis. Sucrose has glass transition temperature of ~58 °C and trehalose has ~115 °C. It is quite interesting to study the phase behavior of varied sucrose to trehalose fractions as it allows us to form microemulsion glasses with tunable glass transition temperatures so that they can be used for varied temperature applications. Figure 5.3 shows the phase behaviors of sugar-oil mixtures containing 40:60 and 60:40 sucrose:trehalose ratios on volume basis, which are very similar to the phase behavior of sugar-oil mixtures containing 50:50 sucrose:trehalose ratio. Phase behavior does not change significantly with varying sucrose to trehalose volume ratio due to the similar hydrophilic nature of sucrose and trehalose molecule and this approach allows us to form microemulsion glasses with higher glass transition temperature up to 82 °C (Figure 5.11).

5.3.3 Characterization of Anhydrous Microemulsion Glasses

5.3.3.1 Small Angle Neutron Scattering (SANS)

Although solids at room temperature, the structure of sugar-oil microemulsions is similar to that of liquid water-oil microemulsions. Their small angle neutron scattering

(SANS) spectra (Figure 5.4 and Figure 5.5) is consistent with that of bicontinuous microemulsions, and can be fit well with the classical Teubner-Strey model102 to yield domain sizes (d) of 22 to 28 nm and correlation lengths (ζ) of ~10 nm that are typical of aqueous microemulsions116. Matching the Ginzburg-Landau free energy expression that underlies the Teubner-Strey model to a Gaussian random field model117, 118 yields a renormalized bending modulus (κR) of ~0.95 kT, also typical of aqueous microemulsions.

73 50:50 (sucrose:trehalose) 60:40 (sucrose:trehalose) 0.64 40:60 (sucrose:trehalose) 2Φ ε) 0.62

0.60 1Φ 6.38×10-6 cm2/s (60% sucrose)

0.58 6.66×10-6 cm2/s (40% sucrose) C18 Surfactant Fraction ( Surfactant Fraction C18

0.56 2Φ

0.16 0.17 0.18 0.19 0.20 0.21 Surfactant Mass Fraction (γ)

Figure 5.3 Comparison of phase diagrams of molten sugar – limonene microemulsion glasses at 365 K with varying sugars ratio of sucrose:trehalose from 50:50 to 40:60 and

74 100

10 Intensity

1 F: d=28.3 nm; ζ=10.9 nm E: d=27.6 nm; ζ=10.9 nm C: d=25.1 nm; ζ=10.3 nm

0.1 0.01 0.02 0.03 0.05 0.07 0.1 q (Å-1)

Figure 5.4 SANS spectra of solid microemulsion glasses at room temperature corresponding to compositions F, E, and C in the phase diagram shown in Figure 5.2a.

Solid lines are fits to the Teubner-Strey model. which yield domain sizes (d) ranging from 25 to 28 nm and correlation lengths (ζ) of ~10 nm.

75 1000

100

10 Intensity

1 Β: d=22.0 nm; ζ=10.2 nm C: d=25.1 nm; ζ=10.3 nm D: d=22.9 nm; ζ=10.6 nm

0.1 0.01 0.1

q (Å-1)

Figure 5.5 SANS spectra of solid microemulsion glasses at room temperature corresponding to compositions B, C, and D in the phase diagram shown in Figure 5.2a.

Solid lines are fits to the Teubner-Strey model. which yield domain sizes (d) ranging from 22 to 25 nm and correlation lengths (ζ) of ~10 nm.

76 The high viscosity of the sugar domains in the molten state does not alter significantly the bending moduli of the surfactant-covered interface. These SANS measurements also confirm that the optical clarity of these oil/sugar glasses is not the result of fortuitous refractive index matching. Figure 5.6 shows domain size of the microemulsion glasses decreases monotonically with increasing surfactant concentration which is in agreement with the packing of larger interfacial area in a fixed volume.

Figure 5.7 and Figure 5.8 show the small angle neutron scattering spectra of the composition points shown by the star in the phase diagram (Figure 5.3) of sucrose to trehalose volume ratios of 60:40 and 40:60 respectively. Small angle neutron scattering data are consistent with that of bicontinuous microemulsions, and can be fit well with the classical Teubner-Strey model102 to yield domain sizes (d) of 22 to 28 nm and correlation lengths (ζ) of ~10 nm that are typical of aqueous microemulsions116.

5.3.3.2 Self-Diffusion Coefficient Measurements (Using MRI)

Even in the solid glass state at room temperature, the limonene oil present in the microemulsion glasses exhibits liquid-like self-diffusion coefficients that point to a sponge-like structure continuous in both solid sugar glass and liquid oil119. Using magnetic resonance imaging (MRI), to exclude cracks in the samples (Figure 5.9a), we observed limonene self-diffusion coefficients that increase from 3.0×10-6 to 6.3×10-6 cm2/s (Figure 5.2b) with increasing oil loading from α=0.3 to α=0.5, respectively. In comparison, pure liquid limonene has a self-diffusion coefficient of 1.3×10-6 cm2/s at the same temperature. The spatial selectivity of self-diffusion coefficient measurements by

MRI does come at the loss of chemical shift selectivity. We verified that the measured self-diffusion coefficients are solely that of the limonene oil and exclusive of

29 F

28 E

d (nm)

24 0.16 0.17 0.18 0.19 0.20 0.21

Surfactant Mass Fraction (γ)

Figure 5.6 Variation of domain size of microemulsion glasses with increasing surfactant concentration of the composition points F, E and C in Figure 5.2(a).

78 1000 γ=20%; ε=57%; d=22.3 nm; ζ=10.2 nm γ=20%; ε=58.5%; d=26.6 nm; ζ=8.8 nm γ=20%; ε=62%; d=23.7 nm; ζ=10.7 nm

100

Intensity 10

0.01

q (Å-1)

Figure 5.7 SANS spectra of solid microemulsion glasses at room temperature corresponding to compositions shown by the star in the phase diagram shown in Figure

79 1000 γ=20%; ε=57%; d=24.0 nm; ζ=9.9 nm γ=20%; ε=58.5%; d=28.2 nm; ζ=8.3 nm γ=20%; ε=62%; d=23.7 nm; ζ=9.6 nm

100

Intensity 10

0.01

q (Å-1)

Figure 5.8 SANS spectra of solid microemulsion glasses at room temperature corresponding to compositions shown by the star in the phase diagram shown in Figure

80 a

c 0.0

-0.2

-0.4

) -0.6 o

-0.8

Ln (A/A -1.0

-1.2

-1.4

-1.6 0 50 100 150 200 250

γ2g2δ2(Δ-δ/3) x1000 s/cm2

Figure 5.9 MRI imaging and self-diffusion coefficient measurement of microemulsion glasses. (a) MRI (H1 intensity) of the cross-section of microemulsion glasses contained in a hexagonal array of 7 tubes each similar to that shown in Figure 5.1. All samples contain 50:50 mass ratio of limonene oil to sugar. Sample A was prepared using deuterated toluene instead of limonene. Samples B-G are microemulsion glasses prepared within the one phase region of the limonene phase diagram (Figure 5.2). (b) The self-diffusion measurements were performed using a conventional spin-echo pulse sequence. (c) The slope of the normalized spin echo intensity relative to the field gradient (g), gradient duration (δ), time delay (Δ), and proton gyromagnetic ratio (γ) as shown here for sample C (Figure 5.2a) yields a room temperature self-diffusion coefficient of 6.3×10-6 cm2/s.

81 contributions from the surfactant chains by preparing a comparable microemulsion glass using deuterated toluene. This sample yields no measurable proton signal from the surfactant alkyl chains (tube A in Figure 5.9a) because of extensive linewidth broadening arising from their slow dynamics. Thus, the measured diffusion coefficient is solely that of the liquid oil present within the bicontinuous glass structure.

5.3.3.3 Rheology

Structural relaxation processes in bicontinuous aqueous microemulsions is generally too rapid to probe rheologically. Retardation of structural relaxation in molten microemulsion glasses by the high viscosity of the sugar domains however, does permit their study using a sealed rheological cell in which the microemulsions are prepared in- situ. We constructed a master curve of the elastic and viscous moduli by time- temperature superposition using the Williams-Landel-Ferry (WLF) equation120 (Figure

5.10) to probe the dynamics of microemulsion glasses as they transition from molten to solid glass states. The WLF equation has been shown to be useful for systems near their glass transition temperature121, which is corroborated here. For sample C (Figure 5.2a), the terminal relaxation time was directly measured at 365 K from the inverse of the crossover frequency to be 1.3 s and increasing to 6300 s at 335 K (determined by time- temperature superposition). In all, the rheological response confirms the transition of a viscoelastic fluid to a glass as the glass transition temperature is approached.

5.3.3.4 Glass Transition Temperature Measurements (Using MDSC)

Within the one-phase microemulsion channel shown in Figure 5.2b, the midpoint heating glass transition (Tg, mph) of the sugars, as measured by modulated differential

Figure 5.10 Master curve of the elastic and viscous moduli for sample C (Figure 5.2a) by time-temperature superposition using the Williams-Landel-Ferry (WLF) equation.

83 scanning calorimetry (MDSC), increases asymptotically from 325 to 358 K as the oil loading decreases from α=60 wt% to 0 wt% (Figure 5.11). This decrease in the glass transition temperature with increasing oil loading is consistent with the depression of melting and glass transition temperatures of liquids confined in pores122, 123. Extracting a length-scale of cooperativity for the glass transition of sugars in these microemulsion glasses is obscured however, by the simultaneous changes in surfactant concentration necessary to stay within the one-phase channel and the accompanying changes in topology of the sugar domains with variations in oil loading.

Figure 5.12 shows the effect of increasing trehalose fraction on the glass transition temperature of microemulsion glasses. As discussed in phase behavior studies, equimolar ratio of sucrose to trehalose is the key to prevent the crystallization inside these sugar based microemulsion glasses. However, there are no signs of crystallization in the microemulsion glasses for replacing sucrose to trehalose volume fraction up to

40:60. Replacing sucrose (Tg~58 °C) by trehalose (Tg~115 °C) by 10 vol% increases the glass transition temperature from 59 °C to 82 °C so that these microemulsion glasses can be used for higher temperature applications up to 80 C.

5.3.3.5 Scanning Electron Microscopy (SEM) Imaging

Samples for scanning electron microscopy imaging are prepared by vacuum drying of the oil trapped inside the interstices of the microemulsion glasses. Vacuum dried microemulsion glasses are sputter coated with 1-2 nm platinum and visualized using scanning electron microscopy at room temperature. Figure 5.13 shows that vacuum dried microemulsion glasses remain wholly intact and do not collapse during the vacuum

Figure 5.11 Reversible heat capacity and midpoint heating glass transition temperatures of microemulsion glasses within the one phase channel (Fig. 2b) for varying oil loadings

(α).

Tg ~ 59 oC 50% trehalose

Tg ~ 82 oC

Rev Cp

60% trehalose

40 50 60 70 80 90 100

Temp (oC)

Figure 5.12 Effect of increasing trehalose fraction (from sucrose:trehalose volume ratio of 50:50 to sucrose:trehalose ratio of 40:60) on the glass transition temperature of microemulsion glass.

86 300 nm

Figure 5.13 SEM image of the vacuum dried microemulsion glass shown in Figure 1.

87 drying. The size and shape of the interconnected sugar and surfactant structures are in agreement with those of freeze fracture electron microscopy of the aqueous bicontinuous microemulsions reported by Jahn and coworkers34, 124. However, the approximate diameter of the sugar domains obtained from SEM imaging (~60 nm) is significantly larger than the domain size (~25 nm) obtained from Teubner-Strey102 analysis of the small angle neutron scattering data shown in Figure 5.3 (sample C).

However, real space computer simulations confirm that these domain sizes are similar when the volume fraction of sugar and oil are same125. In addition, there are disagreeing reports that the freeze fraction electron microscopy images reported by Jahn et al.34, 124 are possibly due to the sample preparation procedures126.

These vacuum dried microemulsion glasses can be easily refilled under vacuum with any monomers or solvents which do not dissolve the sugar matrix. This refilling approach provides a unique opportunity to prepare microemulsion glasses with different functionality oils without studying the rigorous time consuming phase behavior studies of sugar glasses.

5.4 Conclusions

This chapter discusses the self-assembly of sucrose ester surfactants in anhydrous sugar- oil mixtures. In particular, we have presented here a novel direct mixing approach which facilitates the spontaneous formation of molten microemulsion glasses containing more than 50 vol% of oil. Prepared sugar-oil glasses are remarkably clear and solid-like at room temperature. Phase behavior studies and characterization techniques confirm the formation of bicontinuous structures (nanometer-size domains of sugars and liquid oil) inside these sugar-oil microemulsion glasses. Even though these sugar based

88 microemulsions are solid, their phase behavior and microstructures are very similar to that of aqueous based microemulsions. The low cost, water solubility, low toxicity and stabilizing properties of glassy sugars make sugar based microemulsion glasses ideal water replacements for many pharmaceutical, food and materials synthesis applications.

89 Chapter 6 Conclusions

This dissertation discusses self-assembly of sugar based surfactants in aqueous and non-aqueous sugar-oil mixtures. In particular, we have facilitated the spontaneous formation of anhydrous microemulsion glasses containing more than 50 vol% of oil by detailed phase behavior studies of concentrated sugar based aqueous microemulsions.

Significant findings of research studies on aqueous and non-aqueous sugar based microemulsions are summarized as follows:

6.1 Sugar Based Aqueous Microemulsions

We have studied the phase behavior and microstructures of edible microemulsions of d-limonene (orange oil) with concentrated sugar solutions (>65 wt%) using sucrose laurate and sucrose oleate as surfactants. The phase behavior of these mixtures is reported as a function of temperature and surfactant composition, identifying the specific effects of sugar concentration, surfactant chain length, and oil loading on the formation of one phase microemulsion and lamellar phases. Small-angle neutron scattering experiments confirm the presence of well-structured microemulsions with domain sizes ranging from ~35 to 60 nm. With few exceptions, the patterns of microemulsion phase behavior with concentrated sugar solutions are very similar to that of aqueous systems.

These studies simulate the effect of either increasing sugar concentrations or removing water (e.g. spray drying) on the one phase microemulsion region. In addition to providing better understanding of the underlying phenomena of formation of sugar based anhydrous microemulsion glasses, these aqueous sugar based microemulsions have

90 potential applications in encapsulation of hydrophobic and hydrophilic actives, which are used in food, pharmaceuticals and many other industries.

6.2 Sugar Based Non-aqueous Microemulsions

Our study reveals that anhydrous powders of sugars and surfactants suspended in oil spontaneously form molten microemulsion glasses with nanometer-size domains of sugar and liquid oil without mixing. Prepared sugar-oil glasses are remarkably clear and solid- like at room temperature, which however contain more than 50 vol% of liquid oil. Even though these sugar based microemulsions are solid, their phase behavior and microstructures are very similar to that of reported aqueous based microemulsions. These microemulsion glasses are very stable and we have not seen any signs of either phase separation or crystallization of sugars when kept for over two years. The low cost, water solubility, low toxicity and stabilizing properties of glassy sugars make them ideal water replacements for many pharmaceutical, food and materials synthesis applications.

91 Chapter 7 Proposed Future Work

Our recent results on self-assembled sugar-oil complex glasses demonstrate that self- assembly is not limited to the aqueous systems. Nonetheless, investigating self-assembly in sugar-oil mixtures is still in the preliminary stages and there remains a lot of exciting work to be done. For example, investigating phase behavior and structure of liquid crystalline sugar-oil glasses, oil in sugar micellar phases and sugars in oil reverse micellar phases. This broad spectrum of sugar-oil structures can have applications ranging from encapsulating either hydrophilic or hydrophobic actives to optical and sensor devices.

The robust and stable microstructure of sugar-oil glasses discussed in chapter 5 can be used as templates for nanomaterial synthesis. For example, replacing the oil with polymerizable monomers such as acrylates, tetrafluoroethylene to create the complementary templates of the sugar matrix and these templates can be easily obtained upon polymerization simply by washing unreacted sugar and sugar based surfactants with excess amount of water as sugars and sugar based surfactants are readily soluble in water.

The sugar domains of the sugar-oil glasses can be cross-linked by reactions with multifunctional isocyanates to form nonporous polyurethane membranes.

Sugars in sugar-oil glasses can be replaced in part with sugar substitutes or artificial sweeteners for the low calorie food applications. Food additives such as sodium citrate can be used to replace the sugars in part to increase the glass transition temperature of sugar-oil glasses so that they can be used for higher temperature applications127.

92 Bibliography

1. Chow, P. Y.; Gan, L. M., Microemulsion polymerizations and reactions. In

Polymer Particles, Springer-Verlag Berlin: Berlin, 2005; Vol. 175, pp 257-298.

2. Paul, B. K.; Moulik, S. P., Microemulsions: An overview. Journal of Dispersion

Science and Technology 1997, 18, (4), 301-367.

3. Chew, C. H.; Li, T. D.; Gan, L. H.; Quek, C. H.; Gan, L. M., Bicontinuous- nanostructured polymeric materials from microemulsion polymerization. Langmuir 1998,

14, (21), 6068-6076.

4. Lawrence, M. J.; Rees, G. D., Microemulsion-based media as novel drug delivery systems. Advanced Drug Delivery Reviews 2000, 45, (1), 89-121.

5. Gao, F.; Ho, C. C.; Co, C. C., Sugar-based microemulsion glass templates.

Journal of the American Chemical Society 2004, 126, (40), 12746-12747.

6. Gao, F.; Ho, C. C.; Co, C. C., Polymerization in bicontinuous microemulsion glasses. Macromolecules 2006, 39, (26), 9467-9472.

7. Jonsson, B.; Lindman, B.; Holmberg, K.; Kronberg, B., Surfactants and Polymers in Aqueous Solution. John Wiley: Chichester ; New York, 1998.

8. Swarup, S.; Schoff, C. K., A Survey of Surfactants in Coatings Technology.

Progress in Organic Coatings 1993, 23, (1), 1-22.

9. Dill, K. A., The Meaning of Hydrophobicity. Science 1990, 250, (4978), 297-297.

10. Kumar, P.; Mittal, K. L., Handbook of Microemulsion Science and Technology.

CRC Press: New York -Basel, 1999.

11. Blokzijl, W.; Engberts, J., Hydrophobic Effects - Opinions And Facts.

Angewandte Chemie-International Edition 1993, 32, (11), 1545-1579.

93 12. Evans, D. F.; Wennerstrom, H., The Colloidal Domain: Where Physics,

Chemistry, Biology, and Technology Meet. Wiley-VCH: New York, 1999.

13. Hyde, S. T., Curvature and the Global Structure of Interfaces in Surfactant-Water

Systems. Journal De Physique 1990, 51, (23), C7209-C7228.

14. Antonietti, M.; Forster, S., Vesicles and liposomes: A self-assembly principle beyond lipids. Advanced Materials 2003, 15, (16), 1323-1333.

15. Rodriguez-Hernandez, J.; Checot, F.; Gnanou, Y.; Lecommandoux, S., Toward

'smart' nano-objects by self-assembly of block copolymers in solution. Progress in

Polymer Science 2005, 30, (7), 691-724.

16. Allen, D. K.; Tao, B. Y., Carbohydrate-Alkyl Ester Derivatives As Biosurfactants.

Journal of Surfactants and Detergents 1999, 2, (3), 383-390.

17. Graf, A.; Ablinger, E.; Peters, S.; Zimmer, A.; Hook, S.; Rades, T.,

Microemulsions containing lecithin and sugar-based surfactants: Nanoparticle templates for delivery of proteins and peptides. International Journal of Pharmaceutics 2008, 350,

(1-2), 351-360.

18. Hill, K.; Rhode, O., Sugar-Based Surfactants For Consumer Products and

Technical Applications. Fett-Lipid 1999, 101, (1), 25-33.

19. Noiret, N.; Benvegnu, T.; Plusquellec, D., Surfactants From Renewable

Resources. Actualite Chimique 2002, (11-12), 70-75.

20. Uchegbu, I. F.; Vyas, S. P., Non-Ionic Surfactant Based Vesicles (Niosomes) In

Drug Delivery. International Journal of Pharmaceutics 1998, 172, (1-2), 33-70.

94 21. von Rybinski, W.; Hill, K., Alkyl Polyglycosides - Properties and Applications of

A New Class of Surfactants. Angewandte Chemie-International Edition 1998, 37, (10),

1328-1345.

22. Ware, A. M.; Waghmare, J. T.; Momin, S. A., Alkylpolyglycoside: Carbohydrate

Based Surfactant. Journal of Dispersion Science and Technology 2007, 28, (3), 437-444.

23. Shinoda, K.; Carlsson, A.; Lindman, B., On the importance of hydroxyl groups in the polar head-group of nonionic surfactants and membrane lipids. Advances in Colloid and Interface Science 1996, 64, 253-271.

24. Baker, I. J. A.; Matthews, B.; Suares, H.; Krodkiewska, I.; Furlong, D. N.; Grieser,

F.; Drummond, C. J., Sugar fatty acid ester surfactants: Structure and ultimate aerobic biodegradability. Journal of Surfactants and Detergents 2000, 3, (1), 1-11.

25. Matsumura, S.; Imai, K.; Yoshikawa, S.; Kawada, K.; Uchibori, T., Surface-

Activities, Biodegrability And Antimicrobial Properties Of Normal-Alkyl Glucosides,

Mannosides And Galactosides. Journal of the American Oil Chemists Society 1990, 67,

(12), 996-1001.

26. Stubenrauch, C., Sugar Surfactants - Aggregation, Interfacial, and Adsorption

Phenomena. Current Opinion in Colloid & Interface Science 2001, 6, (2), 160-170.

27. Strey, R., Phase Behavior and Interfacial Curvature In Water-Oil-Surfactant

Systems. Current Opinion in Colloid & Interface Science 1996, 1, (3), 402-410.

28. Kahlweit, M., The Phase - Behavior of Systems of The Type H20 - Oil - Nonionic

Surfactant - Electrolyte. Journal of Colloid and Interface Science 1982, 90, (1), 197-202.

95 29. Kahlweit, M.; Strey, R.; Firman, P.; Haase, D.; Jen, J.; Schomacker, R., General

Patterns of The Phase-Behavior of Mixtures of H2O, Nonpolar-Solvents, Amphiphiles, and Electrolytes .1. Langmuir 1988, 4, (3), 499-511.

30. Kahlweit, M.; Busse, G., Tricritical Points and Wetting - Nonwetting Transitions

In Nonionic Microemulsions. Journal of Physical Chemistry B 2000, 104, (20), 4939-

4943.

31. Kahlweit, M.; Lessner, E.; Strey, R., Influence of The Properties of The Oil and

The Surfactant On The Phase - Behavior of Systems of The Type H20 - Oil - Nonionic

Surfactant. Journal of Physical Chemistry 1983, 87, (24), 5032-5040.

32. Kahlweit, M.; Strey, R., Phase-Behavior of Ternary-Systems of The Type H2O-

Oil-Nonionic Amphiphile (Microemulsions). Angewandte Chemie-International Edition in English 1985, 24, (8), 654-668.

33. Kahlweit, M.; Strey, R.; Firman, P., Search For Tricritical Points In Ternary -

Systems - Water Oil Nonionic Amphiphile. Journal of Physical Chemistry 1986, 90, (4),

671-677.

34. Kahlweit, M.; Strey, R.; Haase, D.; Kunieda, H.; Schmeling, T.; Faulhaber, B.;

Borkovec, M.; Eicke, H. F.; Busse, G.; Eggers, F.; Funck, T.; Richmann, H.; Magid, L.;

Soderman, O.; Stilbs, P.; Winkler, J.; Dittrich, A.; Jahn, W., How To Study

Microemulsions. Journal of Colloid and Interface Science 1987, 118, (2), 436-453.

35. Kahlweit, M.; Strey, R.; Schomacker, R.; Haase, D., General Patterns of The

Phase-Behavior of Mixtures of H2O, Nonpolar-Solvents, Amphiphiles, and

Electrolytes .2. Langmuir 1989, 5, (2), 305-315.

96 36. Schubert, K. V.; Kaler, E. W., Nonionic Microemulsions. Berichte Der Bunsen-

Gesellschaft-Physical Chemistry Chemical Physics 1996, 100, (3), 190-205.

37. Sottmann, T.; Strey, R., Evidence of Corresponding States In Ternary

Microemulsions of Water-Alkane-C(i)E(j). Journal of Physics-Condensed Matter 1996, 8,

(25A), A39-A48.

38. Ryan, L. D.; Kaler, E. W., Effect of Alkyl Sulfates On The Phase Behavior and

Microstructure of Alkyl Polyglucoside Microemulsions. Journal of Physical Chemistry B

1998, 102, (39), 7549-7556.

39. Ryan, L. D.; Kaler, E. W., Microstructure Properties of Alkyl Polyglucoside

Microemulsions. Langmuir 1999, 15, (1), 92-101.

40. Ryan, L. D.; Kaler, E. W., The Effect of Anomeric Head Groups, Surfactant

Hydrophilicity, and Electrolytes On N-Alkyl Monoglucoside Microemulsions. Journal of

Colloid and Interface Science 1999, 210, (2), 251-260.

41. Fukuda, K.; Olsson, U.; Ueno, M., Microemulsion Formed By Alkyl

Polyglucoside and An Alkyl Glycerol Ether With Weakly Charged Films. Colloids and

Surfaces B-Biointerfaces 2001, 20, (2), 129-135.

42. Sottmann, T.; Kluge, K.; Strey, R.; Reimer, J.; Soderman, O., General Patterns of

The Phase Behavior of Mixtures of H2O, Alkanes, Alkyl Glucosides, and Cosurfactants.

Langmuir 2002, 18, (8), 3058-3067.

43. Chai, J. L.; Li, G. Z.; Diao, Z. Y.; Zhang, G. Y., Studies On Phase Behavior of

Alkyl Polyglucoside Based On Microemulsions With Modified Fishlike Phase Diagram.

Chinese Chemical Letters 2004, 15, (3), 361-364.

97 44. Chai, J. L.; Wang, S. Q.; Li, G. Z.; Xu, Q.; Gao, Y. H., Kinetics of The

Esterification Reaction Catalyzed By Lipase In W/O Microemulsions of Alkyl

Polyglucoside. Chinese Chemical Letters 2004, 15, (6), 699-702.

45. Chai, J. L.; Gao, Y. H.; Qang, J. S.; Li, G. Z.; Zhang, G. Y.; Xu, Q., Kinetics of

Esterication Reaction Catalyzed By Lipase In W/O Microemulsions of Alkyl

Polyglucoside. Acta Chimica Sinica 2004, 62, (19), 1894-1900.

46. Xu, J.; Gao, Y. H.; Zhao, K. S.; Wei, S. X.; Chai, J. L.; Li, G. Z.; Zhang, G. Y.,

Unique Dielectric Behavior of Alkyl Polyglucoside/N-Butanol/N-Hexane/Water System.

Chinese Journal of Chemistry 2005, 23, (12), 1625-1630.

47. Chai, J. L.; Yang, X. D.; Gao, Y. H.; Wu, C. J., Studies on The Middle Phase

Microemulsion of Alkyl Polyglucoside. Indian Journal of Chemistry Section a-Inorganic

Bio-Inorganic Physical Theoretical & Analytical Chemistry 2007, 46, (7), 1075-1080.

48. Wellert, S.; Karg, M.; Imhof, H.; Steppin, A.; Altmann, H. J.; Dolle, M.; Richardt,

A.; Tiersch, B.; Koetz, J.; Lapp, A.; Hellweg, T., Structure of biodiesel based bicontinuous microemulsions for environmentally compatible decontamination: A small angle neutron scattering and freeze fracture electron microscopy study. Journal of

Colloid and Interface Science 2008, 325, (1), 250-258.

49. Kahlweit, M.; Busse, G.; Faulhaber, B., Preparing Microemulsions With Alkyl

Monoglucosides and The Role of N-Alkanols. Langmuir 1995, 11, (9), 3382-3387.

50. Kahlweit, M.; Busse, G.; Faulhaber, B., Preparing Nontoxic Microemulsions With

Alkyl Monoglucosides and The Role of Alkanediols As Cosolvents. Langmuir 1996, 12,

(4), 861-862.

98 51. Ryan, L. D.; Schubert, K. V.; Kaler, E. W., Phase Behavior of Microemulsions

Made With N-Alkyl Monoglucosides and N-Alkyl Polyglycol Ethers. Langmuir 1997, 13,

(6), 1510-1518.

52. Ryan, L. D.; Kaler, E. W., Role of Oxygenated Oils In N-Alkyl Beta-D-

Monoglucoside Microemulsion Phase Behavior. Langmuir 1997, 13, (20), 5222-5228.

53. Hill, K.; Von Rybinski, W.; Stoll, G., Alkyl Polyglucosides: Technology,

Properties and Applications. VCH: New York, 1997; p 1-7.

54. Balzer, D., Cloud Point Phenomena In The Phase-Behavior of Alkyl

Polyglucosides In Water. Langmuir 1993, 9, (12), 3375-3384.

55. Balzer, D., Properties of alkyl polyglucosides. Tenside Surfactants Detergents

1996, 33, (2), 102-&.

56. Kocherbitov, V.; Soderman, O., Phase diagram and physicochemical properties of the n-octyl alpha-D-glucoside/water system. Physical Chemistry Chemical Physics 2003,

5, (23), 5262-5270.

57. Kocherbitov, V.; Soderman, O.; Wadso, L., Phase diagram and thermodynamics of the n-octyl beta-D-glucoside/water system. Journal of Physical Chemistry B 2002, 106,

(11), 2910-2917.

58. Nilsson, F.; Soderman, O.; Johansson, I., Physical-chemical properties of the n- octyl beta-D-glucoside/water system. A phase diagram, self-diffusion NMR, and SAXS study. Langmuir 1996, 12, (4), 902-908.

59. Nilsson, F.; Soderman, O.; Reimer, J., Phase separation and aggregate-aggregate interactions in the C(9)G(1)/C(10)G(1) beta-alkyl glucosides water system. A phase diagram and NMR self-diffusion study. Langmuir 1998, 14, (22), 6396-6402.

99 60. Ryan, L. D.; Kaler, E. W. In Alkyl polyglucoside microemulsion phase behavior,

2001; Elsevier Science Bv: 2001; pp 69-83.

61. Fukuda, K.; Soderman, O.; Lindman, B.; Shinoda, K., Microemulsions Formed

By Alkyl Polyglucosides And An Alkyl Glycerol Ether. Langmuir 1993, 9, (11), 2921-

2925.

62. Kahlweit, M.; Busse, G.; Faulhaber, B., Preparing nontoxic microemulsions .2.

Langmuir 1997, 13, (20), 5249-5251.

63. Herrington, T. M.; Sahi, S. S., Phase-Behavior Of Some Sucrose Surfactants With

Water and N-Decane. Journal of the American Oil Chemists Society 1988, 65, (10),

1677-1681.

64. Kabir, H.; Aramaki, K.; Ishitobi, M.; Kunieda, H., Cloud point and formation of microemulsions in sucrose dodecanoate systems. Colloids and Surfaces a-

Physicochemical and Engineering Aspects 2003, 216, (1-3), 65-74.

65. Asim, N.; Radiman, S.; bin Yarmo, M. A., Synthesis of WO3 in nanoscale with the usage of sucrose ester microemulsion and CTAB micelle solution. Materials Letters

2007, 61, (13), 2652-2657.

66. Bolzinger, M. A.; Carduner, T. C.; Poelman, M. C., Bicontinuous sucrose ester microemulsion: A new vehicle for topical delivery of niflumic acid. International Journal of Pharmaceutics 1998, 176, (1), 39-45.

67. Desai, N. B.; Lowicki, N., New Sucrose Esters and Their Applications In

Cosmetics. Cosmetics & Toiletries 1985, 100, (6), 55-59.

100 68. Fanun, M.; Leser, M.; Aserin, A.; Garti, N., Sucrose ester microemulsions as microreactors for model Maillard reaction. Colloids and Surfaces a-Physicochemical and

Engineering Aspects 2001, 194, (1-3), 175-187.

69. Garti, N.; Aserin, A.; Fanun, M. In Non-ionic sucrose esters microemulsions for food applications. Part 1. Water solubilization, 2000; Elsevier Science Bv: 2000; pp 27-

38.

70. Garti, N.; Clement, V.; Fanun, M.; Leser, M. E., Some characteristics of sugar ester nonionic microemulsions in view of possible food applications. Journal of

Agricultural and Food Chemistry 2000, 48, (9), 3945-3956.

71. Khiew, P. S.; Huang, N. M.; Radiman, S.; Ahmad, M. S., Synthesis of NiS nanoparticles using a sugar-ester nonionic water-in-oil microemulsion. Materials Letters

2004, 58, (5), 762-767.

72. Khiew, P. S.; Radiman, S.; Huang, N. M.; Ahmad, M. S., Studies on the growth and characterization of CdS and PbS nanoparticles using sugar-ester nonionic water-in- oil microemulsion. Journal of Crystal Growth 2003, 254, (1-2), 235-243.

73. Thevenin, M. A.; Grossiord, J. L.; Poelman, M. C., Sucrose esters cosurfactant microemulsion systems for transdermal delivery: Assessment of bicontinuous structures.

International Journal of Pharmaceutics 1996, 137, (2), 177-186.

74. Riva, S.; Chopineau, J.; Kieboom, A. P. G.; Klibanov, A. M., Protease-Catalyzed

Regioselective Esterification Of Sugars and Related-Compounds In Anhydrous

Dimethylformamide. Journal of the American Chemical Society 1988, 110, (2), 584-589.

101 75. Bolzinger-Thevenin, M. A.; Grossiord, J. L.; Poelman, M. C., Characterization of a sucrose ester microemulsion by freeze fracture electron micrograph and small angle neutron scattering experiments. Langmuir 1999, 15, (7), 2307-2315.

76. Fanun, M.; Wachtel, E.; Antalek, B.; Aserin, A.; Garti, N., A study of the microstructure of four-component sucrose ester microemulsions by SAXS and NMR.

Colloids and Surfaces a-Physicochemical and Engineering Aspects 2001, 180, (1-2),

173-186.

77. Garti, N.; Aserin, A.; Tiunova, I.; Fanun, M., A DSC study of water behavior in water-in-oil microemulsions stabilized by sucrose esters and butanol. Colloids and

Surfaces a-Physicochemical and Engineering Aspects 2000, 170, (1), 1-18.

78. Glatter, O.; Orthaber, D.; Stradner, A.; Scherf, G.; Fanun, M.; Garti, N.; Clement,

V.; Leser, M. E., Sugar-ester nonionic microemulsion: Structural characterization.

Journal of Colloid and Interface Science 2001, 241, (1), 215-225.

79. Kabir, M. H.; Ishitobi, M.; Kunieda, H., Emulsion stability in sucrose monoalkanoate system with addition of cosurfactants. Colloid and Polymer Science 2002,

280, (9), 841-847.

80. Keipert, S.; Schulz, G., Microemulsions With Sucrose Fatty Ester Surfactants .1.

In-Vitro Characterization. Pharmazie 1994, 49, (2-3), 195-197.

81. Kunieda, H.; Ushio, N.; Nakano, A.; Miura, M., 3-Phase Behavior In A Mixed

Sucrose Alkanoate and Polyethyleneglycol Alkyl Ether System. Journal of Colloid and

Interface Science 1993, 159, (1), 37-44.

102 82. Nakamura, N.; Yamaguchi, Y.; Hakansson, B.; Olsson, U.; Tagawa, T.; Kunieda,

H., Formation of microemulsion and liquid crystal in biocompatible sucrose alkanoate systems. Journal of Dispersion Science and Technology 1999, 20, (1-2), 535-557.

83. Pes, M. A.; Aramaki, K.; Nakamura, N.; Kunieda, H., Temperature-insensitive microemulsions in a sucrose monoalkanoate system. Journal of Colloid and Interface

Science 1996, 178, (2), 666-672.

84. Rodriguez, C.; Acharya, D. P.; Hinata, S.; Ishitobi, M.; Kunieda, H., Effect of ionic surfactants on the phase behavior and structure of sucrose ester/water/oil systems.

Journal of Colloid and Interface Science 2003, 262, (2), 500-505.

85. Almgren, M.; Swarup, S.; Lofroth, J. E., Effect Of Formamide And Other Organic

Polar-Solvents On The Micelle Formation Of Sodium Dodecyl-Sulfate. Journal of

Physical Chemistry 1985, 89, (21), 4621-4626.

86. Araos, M. U.; Warr, G. G., Self-assembly of nonionic surfactants into lyotropic liquid crystals in ethylammonium nitrate, a room-temperature ionic liquid. Journal of

Physical Chemistry B 2005, 109, (30), 14275-14277.

87. Backlund, S.; Bergenstahl, B.; Molander, O.; Warnheim, T., Aggregation Of

Tetradecyltrimethylammonium Bromide In Water, 1,2-Ethanediol, and Their Mixtures.

Journal of Colloid and Interface Science 1989, 131, (2), 393-401.

88. Belmajdoub, A.; Marchal, J. P.; Canet, D.; Rico, I.; Lattes, A., Formamide, A

Water Substitute .13. Phase-Behavior Of Ctab In Formamide. New Journal of Chemistry

1987, 11, (5), 415-418.

103 89. Bergenstahl, B. A.; Stenius, P., Phase-Diagrams Of Dioleoylphosphatidylcholine

With Formamide, Methylformamide, and Dimethylformamide. Journal of Physical

Chemistry 1987, 91, (23), 5944-5948.

90. Eastoe, J.; Gold, S.; Rogers, S. E.; Paul, A.; Welton, T.; Heenan, R. K.; Grillo, I.,

Ionic liquid-in-oil microemulsions. Journal of the American Chemical Society 2005, 127,

(20), 7302-7303.

91. Friberg, S. E.; Liang, P.; Liang, Y. C.; Greene, B.; Vangilder, R., A Nonaqueous

Lamellar Liquid-Crystal With An Ionic Surfactant Long-Chain Alcohol Combination.

Colloids and Surfaces 1986, 19, (2-3), 249-253.

92. Martino, A.; Kaler, E. W., Phase-Behavior and Microstructure Of Nonaqueous

Microemulsions. Journal of Physical Chemistry 1990, 94, (4), 1627-1631.

93. Martino, A.; Kaler, E. W., Phase-Behavior and Microstructure Of Nonaqueous

Microemulsions .2. Langmuir 1995, 11, (3), 779-784.

94. Schubert, K. V.; Busse, G.; Strey, R.; Kahlweit, M., Microemulsions With

Formamide As Polar-Solvent. Journal of Physical Chemistry 1993, 97, (1), 248-254.

95. Schubert, K. V.; Strey, R., Small-Angle Neutron-Scattering From Microemulsions

Near The Disorder Line In Water Formamide Octane-Ciej Systems. Journal of Chemical

Physics 1991, 95, (11), 8532-8545.

96. Singh, H. N.; Saleem, S. M.; Singh, R. P.; Birdi, K. S., Micelle Formation Of

Ionic Surfactants In Polar Non-Aqueous Solvents. Journal of Physical Chemistry 1980,

84, (17), 2191-2194.

104 97. Warnheim, T.; Jonsson, A., Phase-Diagrams Of Alkyltrimethylammonium

Surfactants In Some Polar-Solvents. Journal of Colloid and Interface Science 1988, 125,

(2), 627-633.

98. Langer, M.; Holtje, M.; Urbanetz, N. A.; Brandt, B.; Holtje, H. D.; Lippold, B. C.,

Investigations on the predictability of the formation of glassy solid solutions of drugs in sugar alcohols. International Journal of Pharmaceutics 2003, 252, (1-2), 167-179.

99. Youngs, T. G. A.; Hardacre, C.; Holbrey, J. D., Glucose solvation by the ionic liquid 1,3-dimethylimidazolium chloride: A simulation study. Journal of Physical

Chemistry B 2007, 111, (49), 13765-13774.

100. Jafari, S. M.; Assadpoor, E.; He, Y. H.; Bhandari, B., Encapsulation efficiency of food flavours and oils during spray drying. Drying Technology 2008, 26, (7), 816-835.

101. Zhang, J.; Liu, G.; Jonas, J., Effects Of Confinement On The Glass-Transition

Temperature Of Molecular Liquids. Journal of Physical Chemistry 1992, 96, (8), 3478-

3480.

102. Teubner, M.; Strey, R., Origin of the Scattering Peak in Microemulsions. Journal of Chemical Physics 1987, 87, (5), 3195-3200.

103. Koehler, R. D.; Schubert, K. V.; Strey, R.; Kaler, E. W., The Lifshitz Line In

Binary-Systems - Structures In Water C(4)E(1) Mixtures. Journal of Chemical Physics

1994, 101, (12), 10843-10849.

104. Schubert, K. V.; Strey, R.; Kline, S. R.; Kaler, E. W., Small-Angle Neutron-

Scattering Near Lifshitz Lines - Transition From Weakly Structured Mixtures To

Microemulsions. Journal of Chemical Physics 1994, 101, (6), 5343-5355.

105 105. Strey, R., Microemulsion Microstructure and Interfacial Curvature. Colloid and

Polymer Science 1994, 272, (8), 1005-1019.

106. Reimer, J.; Soderman, O.; Sottmann, T.; Kluge, K.; Strey, R., Microstructure of

Alkyl Glucoside Microemulsions: Control of Curvature By Interfacial Composition.

Langmuir 2003, 19, (26), 10692-10702.

107. Landau, L. D.; Lifshitz, E. M., Statistical Physics. Pergamon Press: London-Paris,

1958.

108. Kluge, K.; Stubenrauch, C.; Sottmann, T.; Strey, R., Temperature-Insensitive

Microemulsions Formulated From Octyl Monoglucoside and Alcohols: Potential

Candidates For Practical Applications. Tenside Surfactants Detergents 2001, 38, (1), 30-

109. Ryan, L. D.; Kaler, E. W., Alkyl Polyglucoside Microemulsion Phase Behavior.

Colloids and Surfaces a-Physicochemical and Engineering Aspects 2001, 176, (1), 69-83.

110. Kahlweit, M.; Strey, R.; Firman, P.; Haase, D.; Jen, J.; Schomacker, R., General

Patterns of The Phase-Behavior of Mixtures of H2O, Nonpolar - Solvents, Amphiphiles, and Electrolytes .1. Langmuir 1988, 4, (3), 499-511.

111. Kahlweit, M.; Strey, R.; Schomacker, R.; Haase, D., General Patterns of The

Phase-Behavior of Mixtures of H2O, Nonpolar - Solvents, Amphiphiles, and

Electrolytes .2. Langmuir 1989, 5, (2), 305-315.

112. McClain, J. B.; Betts, D. E.; Canelas, D. A.; Samulski, E. T.; DeSimone, J. M.;

Londono, J. D.; Cochran, H. D.; Wignall, G. D.; ChilluraMartino, D.; Triolo, R., Design of nonionic surfactants for supercritical carbon dioxide. Science 1996, 274, (5295), 2049-

2052.

106 113. Cheng, F.; Toury, B.; Lefebvre, F.; Bradley, J. S., Preparation of a mesoporous silicon boron nitride via a non-aqueous sol-gel route. Chemical Communications 2003,

(2), 242-243.

114. Beckett, M. A.; Rugen-Hankey, M. P.; Varma, K. S., Formation of borosilicate glasses from silicon alkoxides and metaborate esters in dry non-aqueous solvents.

Journal of Sol-Gel Science and Technology 2006, 39, (2), 95-101.

115. Niederberger, M.; Garnweitner, G.; Pinna, N.; Neri, G., Non-aqueous routes to crystalline metal oxide nanoparticles: Formation mechanisms and applications. Progress in Solid State Chemistry 2005, 33, (2-4), 59-70.

116. Sottmann, T.; Strey, R.; Chen, S. H., A small-angle neutron scattering study of nonionic surfactant molecules at the water-oil interface: Area per molecule, microemulsion domain size, and rigidity. Journal of Chemical Physics 1997, 106, (15),

6483-6491.

117. Gompper, G.; Endo, H.; Mihailescu, M.; Allgaier, J.; Monkenbusch, M.; Richter,

D.; Jakobs, B.; Sottmann, T.; Strey, R., Measuring bending rigidity and spatial renormalization in bicontinuous microemulsions. Europhysics Letters 2001, 56, (5), 683-

689.

118. Endo, H.; Mihailescu, M.; Monkenbusch, M.; Allgaier, J.; Gompper, G.; Richter,

D.; Jakobs, B.; Sottmann, T.; Strey, R.; Grillo, I., Effect of amphiphilic block copolymers on the structure and phase behavior of oil-water-surfactant mixtures. Journal of Chemical

Physics 2001, 115, (1), 580-600.

107 119. Olsson, U.; Shinoda, K.; Lindman, B., Change of the structure of microemulsions with the hydrophile lipophile balance of nonionic surfactant as revealed by NMR self- diffusion studies. Journal of Physical Chemistry 1986, 90, (17), 4083-4088.

120. Macosko, C. W., Rheology: Principles, Measurement, and Applications. John

Wiley and Sons, Inc.: New York, 1994.

121. Van Krevelen, D. W., Properties of Polymers. Elsevier: Amsterdam, 1994.

122. Arndt, M.; Stannarius, R.; Groothues, H.; Hempel, E.; Kremer, F., Length scale of cooperativity in the dynamic glass transition. Physical Review Letters 1997, 79, (11),

2077-2080.

123. Jackson, C. L.; McKenna, G. B., The Melting Behavior of Organic Materials

Confined in Porous Solids. Journal of Chemical Physics 1990, 93, (12), 9002-9011.

124. Jahn, W.; Strey, R., Microstructure Of Microemulsions By Freeze-Fracture

Electron-Microscopy. Journal of Physical Chemistry 1988, 92, (8), 2294-2301.

125. Chen, S. H.; Chang, S. L.; Strey, R. In Simulation Of Bicontinuous

Microemulsions - Comparison Of Simulated Real-Space Microstructures With Scattering

Experiments, 1991; Munksgaard Int Publ Ltd: 1991; pp 721-731.

126. Green, J. L., Electron-Microscopic Study Of A Glass-Forming Water Oil Pseudo-

3-Component Microemulsion System. Journal of Physical Chemistry 1990, 94, (15),

5647-5649.

127. Kets, E. P. W.; Ijpelaar, P. J.; Hoekstra, F. A.; Vromans, H., Citrate increases glass transition temperature of vitrified sucrose preparations. Cryobiology 2004, 48, (1),

46-54.

108