LECTURE 10 FORMULATION CHEMISTRY SHORT TEST (Formulation) March 12
FINALS Tues., March 19, 9:30-11:30, C114
FORMULATION CHEMISTRY FORMULATION CHEMISTRY
n Formulation chemistry is the mixing of compounds/ substances that do not react with each other but n Many modern products contain a combination of several produce a mixture with the desired characteristics/ chemical substances, each contributing an advantage to properties to suit a particular application/use. the ﬁnished product for a particular application.
FORMULATION CHEMISTRY FORMULATION CHEMISTRY n Any developed product must be commercially viable i.e. a n Since no reactions happen in making the mixture, most useful proﬁtable material, so, almost every example quoted formulations are prepared by measuring liquids by volume and below, you will actually ﬁnd in your home i.e. a broad range of solids by mass ('weight'). It is perfectly possible for a marketed useful household products are the result of the science of product to go on sale without a chemical equation ever being formulation chemistry. written down!
n Although there are no chemical reactions involved in n However, there may be much chemistry going on to actually preparing formulations, there are many chemical make some of the ingredients e.g. chemically synthesising a aspects to do with formulation. These include drug is one matter, mixing it with water and other ingredients thermodynamics (energy changes) of mixing, phase to make a liquid medicine for oral consumption is another! equilibria, solutions, surface chemistry, colloids, emulsions and suspensions.
FORMULATION CHEMISTRY FORMULATION CHEMISTRY
n These important principles and ingredients may be n By changing the composition of the mixture, its related to properties such as adhesion, weather properties will change to be more or less suited to a resistance, texture, shelf-life, biodegradability, particular useful application. Quite a bit of trial and error allergenic response and many other properties. goes into product formulation research and even computer programes have been developed to model and therefore predict the properties a mixture may have - BUT its still got to be tested in the laboratory.
EXAMPLES - PAINTS EXAMPLES - PAINTS
n A paint is made up of a base pigment, a mixture of n Binders bind the pigment to the surface painted and compounds to give it a particular color, a binder and a pigments must be insoluble materials e.g. titanium solvent which evaporates to give a hard solid surface dioxide and zinc oxide are used as white pigments (and ﬁnish (matt or gloss depending on the composition). have replaced potentially harmful lead pigments). Paints may be water, latex, oil, acrylic or epoxy based. Sometimes the binding action involves a chemical House paints must be reasonably durable at a change e.g. polymerisation. Acrylic paints use polymer reasonable price but high durability paints used for car resins as a solvent and can be thinned with water, but and aircraft bodies are more costly. still dry easily.
EXAMPLES – INKS and DYES EXAMPLES – INKS and DYES
There is a huge variety of inks available of diﬀerent Good color quality is required for glossy magazines. As well compositions to suit diﬀerent circumstances. Ink used for as colour composition, appropriate ink ﬂow is important newspapers or paperback novels must be cheap and have for pens and computer printers. The performance and the consistency of a thick sludge to properly feed through formulation of a good photocopier or laser printer toner the ink rollers of a printing press. depends upon its electrostatic properties.
COSMETICS AND OTHER 'PERSONAL PRODUCTS' OTHER EXAMPLES
n The cosmetic industry provides a wide range of Petrolium Oil Products, Detergents (gels, formulated products. In the bathroom/bedroom you may ﬁnd perfumes, moisturizers, lipstick, antiaging skin bars, liquids, granules), Soap (blocks/ products, face powder, nail polish, sunscreen/ powders, liquids), Perfumes and Flavors, sunblocker, hair gel, hair conditioning and colouring Pharmaceutical products, adhesives, products, aftershave and deodorants etc. pesticides, Food industry products, dietary supplements.
What form? What form?
Consumer preferred Solid (granular, block), encapsulated solids Ease of formulation Gels and Paste Cost. Liquids (solutions, emulsions) (dispersions) (dilute or concentrated)
MODE OF USE/DELIVERY PRODUCT AESTHETICS
- direct application - odor, ﬂavor
- dilute and use - Color
- - Spray-on - Form
- With implements (tooth brush, foam) - others
MANUFACTURING IN COSMETICS
FROM THE LABORATORY TO 3/7/13 FULL PRODUCTION
PRIMARY AND SECONDARY BENEFITS
Two in one shampoo Detergents for cleaning but can claim antibacterial beneﬁt. Dishwashing with glass repair
Emulsion Chemistry Emulsion Chemistry OUTLINE – WHAT YOU SHOULD LEARN
n Learn about emulsions Cosmetic Formulation n What they are n Where they are used n How you make them n Practical information
Emulsion Chemistry: Emulsion Chemistry: Cosmetics The Problem - OILS
n Oils are excellent cosmetic materials n Cosmetics are all about changing / n Improve surface feel improving surfaces n Protect n Aid in moisturization n Reduce static n Shine n Don’t wash away n Oils have drawbacks n Tacky, greasy 25 26 n Cost too much
Emulsion Chemistry: Emulsion Chemistry: The Solution – Dilution! The Problem
n Oil & Water Do Not Stay Mixed n Why?
n Lower free energy when separate n Why?
n Hydrogen Bonding
n Oils are non-polar
n Size of molecules
Emulsion Chemistry: Emulsion Chemistry The Solution Emulsiﬁer – The Stabilizer
n Add energy to the system n Lipophilic tails & Hydrophilic heads n Agitation
n Heat n Need something to stabilize Reduce interfacial surface tension n Surfactants or Emulsiﬁers Helps disperse oil in water 29 Forms micelles in solution 30
Emulsion Chemistry: Emulsion Chemistry: Micelle formation The Solution
n Oil breaks into tiny droplets (particles) Molecules in Motion
n Hydrophilic heads align with water
n Lipophilic tails
align with oil 31 32
n Note: More structures than this formed in solution. Depends on surfactant concentration
Emulsion! Common Emulsions
Peanut Butter 33 Milk Salad Dressing 34
Emulsion Chemistry Emulsion Chemistry EMULSIONS EMULSIONS n Pseudo-Stable mixtures of oils & water n Why are they useful? n Three phases n Improved feel
n Internal Phase n Easier to apply – Shear thinning
n External Phase n Less chemical exposure = safer
n Emulsiﬁer n Use the right amount n It’s generally cheaper!
Emulsion Chemistry Emulsion Chemistry EMULSIONS - PARTICLES Emulsions – Particle Size n The importance of particle size Type Particle Size
n Clarity Macroemulsion >1000 nm n Stability Microemulsion 10 – 300 nm n Characterization Micelles 5 – 10 nm n Macroemulsions Solutions <5 nm n Microemulsions (also Nanoemulsions) 37 38
Emulsion Chemistry Emulsion Chemistry EMULSIONS - TYPES Oil in Water – O/W n Type of emulsions n Internal phase = oil
n Oil in Water n External phase = water
n Water in Oil n Advantages
n n Multiple emulsions Easiest to formulate n Least expensive
n Best feel – cooling eﬀect n Disadvantages 39 40 n Less oil delivered
n Not as eﬀective for dry skin
n Not water-resistant
Emulsion Chemistry Example Product – O/W Water in Oil – W/O
n Internal phase = water St. Ives Vitamin E Lotion n External phase = oil
Water (Aqua), Glycerin, Mineral Oil (Paraffinum Liquidum), Stearic n Advantages Acid, Glycol Stearate, Stearamide AMP, Petrolatum, Dimethicone, n Waterprooﬁng possible Tocopherol, Tocopheryl Acetate, Chamomilla Recutita Flower Extract (Matricaria), Helianthus Annuus Extract (Sunflower), Sambucus n Most eﬀective for dry skin Nigra Flower Extract, Primula Veris Extract, Theobroma Cacao Seed n Better stability Butter (Cocoa), Glyceryl Stearate, Cetyl Alcohol, Triethanolamine, Other Products Acetylated Lanolin Alcohol, Cetyl Acetate, Magnesium Aluminum n Disadvantages Hair conditioners Silicate, Carbomer, Propylene Glycol, Propylparaben, Methylparaben, Sunscreen n Oily, tacky feel Wrinkle Creams DMDM Hydantoin, Disodium EDTA, Sorbitol, Fragrance (Parfum), Yellow 5 (CI 19140) n More expensive 41 42
Emulsion Chemistry Example Product – W/O Emulsions – Diﬀerences
Philosophy hope in a tube, Firming cream Water (aqua), Squalane, Mineral Oil, Glycerin, Isocetyl n Is it O/W or W/O? Stearoyl Stearate, Petrolatum, Butylene Glycol, Polyglyceryl 2 Diisostearate, PEG 30 Dipolyhydroxystearate, Ceresin, n Dilution – O/W disperses more easily Polyethylene, Microcrystalline Wax, Magnesium Sulfate, Phytosteryl/Octyldodecyl/Lauroyl Glutamate, Dipalmitoyl n pH – O/W has consistent pH Hydroxyproline, Tocopheryl Acetate, Polysorbate 80, Bisabolol, Potassium Ascorbyl Tocopheryl Phosphate, Iron n Conductivity – O/W conducts electricity Oxide (CI 77492, CI 77491 and CI77499), Methylparaben, Diazolidinyl Urea, Ethylparaben, Tetrasodium EDTA
Emulsion Chemistry Multiple Emulsions EMULSION STABILITY
n Multiple phases
n Oil in Water in Oil (O/W/O)
n Water in Oil in Water (W/O/W) n Advantages
n More eﬀective than Oil in Water
n Less greasy than Water in oil
n Time release, active delivery possible n Disadvantages
n Hard to manufacture 45 46 n Not always stable
Emulsion Chemistry Emulsion Chemistry: Emulsion - Stability Emulsions - Stability Problems
n Emulsions are inherently unstable
n Second Law of Thermodynamics Flocculation Coalescence n Good emulsions last a long time Creaming Inversion
n But eventually, these things happen… 47 48
Emulsion Chemistry Emulsion – Stability EMULSION FORMULATION n Formulators ﬁght the Second Law! n Prolong the life of the product n How?
n Particle Size n Testing for stability
n Viscosity Checks
n Appearance 49 50
Emulsion Chemistry: Emulsion Chemistry: ELEMENTS OF THE FORMULA Emulsions – Oil Phase
n Formula Components n Examples in cosmetics
n Oil Phase n Lanolin and derivatives
n Hydrophobic materials n Natural Oils / Fats
n Oils, esters, fragrances n Waxes
n Aqueous phase n Silicones
n Extracts, colorants n Esters
n Humectants n Emollients (moisturizers) n Thickeners n Emulsiﬁers 51 52 n Holds it all together
Emulsion Chemistry: Emulsion Chemistry: Emulsions – Aqueous Phase Emulsions – Aqueous Phase
n Anything that is soluble in water n Thickeners to stabilize the emulsion n Examples in cosmetics n Examples in cosmetics
n Water n Carbomer
n Hydrolyzed proteins n Locust bean gum
n Humectants n Xanthan gum
n Glycols n Cellulosics
n Extracts n PVP/Decene copolymer
n Polymers, thickeners 53 54 n Acids, etc.
Emulsion Chemistry: Emulsion Chemistry: Emulsions – Emulsiﬁers Typical Emulsiﬁers
n Surfactants n Glyceryl Stearate n Anionic n Carboxylic acids : Soaps n PEG-100 Stearate n Sulfonic acids: Sulfosuccinate esters n Stearyl Alcohol n Cationic n Amines : PEG Alkyl amine n Cetyl Alcohol n Quaternaries: Tetraalkyl ammonium salts n Laureth-23 n Amphoterics Most common n n Steareth Alcohol Phospholipids For Cosmetic n Nonionics Emulsions n Cetyl/PEG/PPG 10 Dimethicone n Fatty Alcohols 55 n 56 n Esters Stearic Acid n Polymers
Emulsion Chemistry: Emulsiﬁers – HLB Emulsions – HLB HYDROPHOBE/LIPOPHOBE BALANCE
n How to pick emulsiﬁers n Varying degrees of non-polar & polar character.
n Mostly, it’s trial and error
Less polar (low HLB) n Modify starting formulas
n Or Learn to use HLB More Polar (High HLB)
n Speciﬁc oils need speciﬁc surfactant polar/non-polar character to be eﬀectively emulsiﬁed. 57 58
Emulsion Chemistry: Emulsion Formulation: HLB System Emulsions – HLB
n HLB system - n William Griﬃn from Uniqema in 1949 n System to quickly create stable emulsions n Works best with nonionic surfactants n Ingredients are assigned an HLB value
n(based on molecular weight & solubility) n Lower values are less water soluble n Oils are assigned HLB values n Amount of emulsiﬁer is calculated Common Oils used and the HLB needed to Create an emulsion
Emulsion Chemistry: Emulsion Chemistry: Emulsions – HLB Emulsions – HLB Formula
Chemical Ethylene Glycol Glyceryl Stearate Sorbitan Palmitate Laureth-4 Nonoxynol-9 Polysorbate-80 • HLB is only a good approximation • Doesn’t always work
• Multiple emulsiﬁers improve stability • More emulsiﬁer is used than needed 61 62
Emulsion Chemistry: EMULSIONS – MAKING THEM Simple Oil In Water Emulsion
n Typical Formulation
n Oil and Water Phase are mixed separately
n Oil phase is heated
n to melt waxes & fatty alcohols
n Mixed with surfactants
n Cooled while being agitated
n this makes the appropriate particle size 63 64
Simple Water in Oil Emulsion Simple Micro Emulsion
Actual Formulation!! Emulsion Making: Scale up
Pilot Plant Equipment
Emulsion Chemistry: Emulsion Chemistry: Emulsions – Summary Emulsions – Where to learn more
n n Emulsion deﬁned Starting Formulas n happi.com n Emulsiﬁcation by surfactants n Allured.com n Types of Emulsions n Harry’s Cosmeticology n Emulsion stability n Rieger: Chemical Publishing co n HLB n Handbook of Cosmetic Science & Technology n Maibach: Marcel Dekker n Emulsion formulation n The Chemistry & Manufacture of Cosmetics n Schlossman: Allured Publishing 69 70
n TYPES OF COSMETIC PRODUCT FORMS COSMETIC PRODUCT FORMS
n COSMETIC R&D LABORATORY & EQUIPMENT FOR n Selection of a proper product form is important in order to achieve FORMULA PREPARATION. the criteria of marketing and technical attributes desired in the ﬁnal system. n STABILITY & TESTING PARAMETERS. n One must balance the desired consumer perceived beneﬁts with the technical ability in the formula to deliver such beneﬁts. n PILOT SCALEUP OF COSMETIC FORMULATIONS AND ASSOCIATED PARAMETERS.
n MANUFACTURING IN THE PLANT ENVIRONMENT
n These are the simplest forms of cosmetic products. Are n In most cases heating and/or cooling are not required to achieve a characterized as liquid systems in which all of the constituents are homogenous solution ; the only thing needed is adequate mixing of soluble. the components. n Solutions can be water or oil based systems and are easy to manufacture as they usually consist of utilizing a single mixing n Even though solutions are easy to produce from a manufacturing vessel where the main diluents is added and then mixing in one perspective, they do possess the downside of oﬀering little ingredient after another. functionality. Many functional cosmetic ingredients have limited or no solubility in water and require other product forms.
n Most cosmetic cream formulations are emulsions which are deﬁned as a heterogeneous system composed of an immiscible liquid n Most (75 % +) of cosmetic creams are of the OIL-IN-WATER type dispersed as droplets in another liquid. with an oil phase ranging from 10%-25%. Typical products that use creams are Shaving products , Skin care, Antiperspirants, etc. n Emulsiﬁed cream products can be O/W or W/O systems depending n Most cream formulations of cosmetic products are well perceived on the continuous phase. by the consumer and have aesthetic appeal.
n However, since this dosage form is an emulsion they are inherently unstable and proper stability testing must be done in the lab before releasing for actual manufacturing on a large scale.
n From a manufacturing perspective lotions are easier to produce as n This is the type of product form that is used in applications, where a they are less viscous and heating and cooling times are lessened. less viscous dosage form is desired from a rheological perspective. n From a rheological perspective, it is important to remember that They can be deﬁned as thin creams. lotions are less stable thermodynamically from creams because the higher viscosity of a cream will slow down the natural destabilizing n As these products are also emulsions in nature they are less greasy forces. to the touch and are lighter in texture to the consumer. n Examples of products that utilize the lotion form are : n Skin and Facial Lotions n Hair Conditioners n Moisturizing Cleansers
OINTMENTS AND PASTES OINTMENTS AND PASTES
n It is important to note that since this product form are essentially n This type of product form is utilized when there is a desire for a oil based systems, they present few stability issues ( outside of formula to be extra viscous in consistency. rancidity or lipid oxidation ) and do not have microbiological contamination issues. n They are thicker than creams and can be total anhydrous systems or n Because of their high viscosity or thickness, problems in contain a very low amount of water. Most are heavy or greasy as manufacturing can arise especially in compounding and ﬁlling. they contain lanolin, petroleum and mineral oil as the main constituents. n Examples of products that are ointments in nature are : n Hair Pomades n Medicated Skin Products n Ethnic Hair Treatment Items
n From a stability perspective, suspensions usually contain either an inorganic thickener or structurizing polymer which “lock” the n This product form is related to emulsions, are usually water-based particles in place. This counteracts instability such as Van Der Waals formulations which contain larger, often visible products or hydrophobe/ lipophobe interactions suspended throughout. n Production of suspensions is generally easier than producing n They can range in viscosity and this type of product form oﬀer a emulsions as separate mixing kettles are rarely required. unique visual eﬀect to the consumer not observed in other n Examples of suspensions are : cosmetic products. n (encapsulated emollients) n By means of suspensions one can deliver non compatible n Sunscreen lotions with titanium dioxide or zinc oxide ingredients. n Calamine lotion n Antiperspirant sticks
n This product form can be deﬁned as clear, shear thinning n In the manufacturing process large scale production is complicated by formulations. They are composed usually of water or alcoholic their high viscosity. AIR entrapment is common place during this solutions gelled or thickened with speciﬁc gelling agents such as manufacturing mode and careful mixing is required to avoid this from natural gums, acrylic polymer or cellulosic type polymers. happening. n Examples of gels include:
n There is a special type of gel system which can be made called a micro n Shower Gels emulsion or “RINGING” gel that vibrates or rings when you tap the n Shaving Gels container. n Toothpastes n Ethnic “Shine” Hair Products (Microemulsion)
n This is a product type which can be used to deliver insoluble n Sticks can be made as a sodium stearate type or as a pure materials such as fragrances, pigments, emollients and stick from high melting point ingredients such as waxes, speciﬁc active ingredients. hydrogenated oils and esters. n They are usually opaque but can, in some cases, be n Stick formulations have good stability proﬁles as their solid formulated as clear products. structure inhibits most destabilizing processes. n Examples of stick personal care products are:
n Deodorant sticks
n Antiperspirant sticks
n Hair styling sticks
n Powders present the simplest form of a solid dosage form. Powders are a relatively stable product form and They consist of solid raw materials blended together in a during the manufacturing process involving ﬁne mixture. specialized mixing equipment, it becomes critical to n Common ingredients that are utilized in the formulation of avoid contamination with water. powders include: n Examples of powder personal care products are:
n Talc n Baby powders
n Starch n Anti-fungal powders n Titanium dioxide n Body talc n Silicates
n In compounding the active materials are mixed with the solvent and then this concentrate is ﬁlled into the can. The n In contrast to the product forms discussed earlier, aerosols propellant is added and the can is sealed. depend more on the packaging for their existence than n Stability issues are primarily of can corrosion and can be the ingredients. prevented by adding corrosion inhibitors to the formula n Aerosols are composed of a concentrate solution that is with high water contents. ﬁlled into a metal can after being pressure-ﬁlled with a n Examples of aerosol personal care products are : propellant that is hydrocarbon or freon based. n Shaving creams
n Hair sprays n Aerosol antiperspirants & deodorants
n Feminine deodorant products
COSMETIC R&D LABORATORY q Pilot scale-up and production of formula with appropriate n The development of aesthetic and chemically stable stability testing. personal care formulations has its origin in the research q Intermediate sized experimental batch and appropriate and development department. stability testing. n The development of such formulations and the ultimate q Selection of proper processing equipment for full manufacturing and production can be visualized in the production-sized run. product development “ CASCADE” of steps as follows : q Process evaluation and validation. n Formulation “ BRAINSTORMING” n Prototype development and panel testing. q What are the needs in the way of equipment for the n Formula optimization and selection for desirable research and development laboratory in order to help aesthetic/ marketing parameters. begin the “product development cascade” of events? n Stability testing of lab prepared samples.
BASIC LABORATORY EQUIPMENT BASIC LABORATORY EQUIPMENT
n Mixer-stirrers either electric or air driven equipped with both propeller and sweep ( simulated) shafts to simulate production n Viscometer capable of processing equipment. determining viscosity of very ﬂuid liquid systems to thick viscous creams and ointments.
• pH meter for assessing specific acidity or alkalinity of a formulation. OPTIONAL LABORATORY EQUIPMENT n Centrifuge for additional analytical and stability testing. n Cone penetrometer for relative “ HARDNESS” of creams, gels, ointments etc. n Analytical instrumentation in conjunction with quality assurance lab equipment for advanced needs. • Heating device ( hot plate or mantle) for preparation of formulations requiring thermal energy. n IR spectro photometer n HPLC n UV-visible Spectro photo meter
n Speciﬁc claim substantiation equipment ( EX- • Refrigerator and/or oven for minimum stability testing of Instron) formulations. n Lab homogenizer
STABILITY PARAMETERS AND TESTING STABILITY PARAMETERS AND TESTING
n Typical stress conditions used by formulators in the hope that product performance and appearance are not n Formulations in R&D routinely examine product stability using various procedures. adversely aﬀected during the projected product shelf life include: n It is rarely possible to predict long term stability of any product, even after repeated examinations of the formula n Heating during and after exposure to artiﬁcially created stress n Freezing conditions. n Centrifugation n Within the cosmetic industry, shelf life projections are based on the formulators assessments of stability data in contrast to much more rigorous analytical testing that is found in the pharmaceutical industry.
n Cosmetic products may exhibit instability due to chemical EMULSION INSTABILITY TYPES changes of the individual chemical components or the n CREAMING presence of undesirable micro-organisms. n Separation into two or more layers having diﬀerent phase concentrations and diﬀerent particle size distributions.
n If one examines the various product forms discussed n Encountered in primarily ﬂuid ( low viscosity) emulsions and earlier in this presentation, creams and lotions that are usually can be minimized by reducing droplet size. Will not emulsions by deﬁnition possess the greatest potential for occur if both phases have the same density. stability problems during the shelf- life of the product.
n EMULSION BREAKDOWN n Cosmetic formulations, especially emulsions dosage forms, n Usually preceded by a sequence of physical processes, are thermodynamically unstable systems. They obey the ﬂocculation and coalescence, and can be caused by: basic laws of physical chemistry and tend to revert to states of lowest free energy. (I.e.- oil and water phases).
• Micro-organisms n Deﬁned as the change from one type of emulsion • pH form to another with the “FLIP” of the continuous • Temperature extremes phase. • Mechanical stresses
n Rare, but can occur in certain types, of o/w systems. n Must monitor stability samples rigorously to Example Borax / Beeswax upon loss of water) determine extent of above physical processes
PREDICTIVE COSMETIC STABILITY TEMPERATURE TESTING OF EMULSIONS n Rule of thumb assumes three months storage at a temperature between 37 degree C and 45 degree n Cosmetic stability testing, in general has to do with the primary concerns of physical appearance and the C products use characteristics. n with no evidence of separation should guarantee stability of the formula at room temperature n Review of main parameters for emulsion instability: ( 25-30 degree Celsius) for one year.
TEMPERATURE n Formulators utilize the examination of rheological change as a predictive tool to assess emulsion n Above rule is based on principles of the arrhenius stability. equation which may not be valid for emulsions.
n This type of stability testing includes the use of n Based on the above it is an accurate point to state that stability testing of emulsions should not be viscometers and/or cone or needle penetrometers. based solely on high temperature testing.
n STABILTY OF ACTIVES IN COSMETICS
n Testing of drug ( active) constituents in emulsions • Particle size measurement of the disperse phase in an using the Arrhenius equation requires storage at two emulsion requires careful interpretation. temperatures at which chemical decomposition may – A continuous increase in particle size should result in occur. The wider the separation between the emulsion instability unless the preparation is very temperatures the more reliable is the analysis. viscous. n The tendency of emulsions to separate at elevated temperatures may have eﬀects on drug solubility and can alter reaction rates.
SUMMARY OF ACCEPTED GUIDELINES FOR OTHER TESTING ACCELERATED STABILITY TESTING
CONDITION TYPE OF ASSESSMENT 25°c ± 2°c One year SHAKING One week at 30°c or 40°c. 30 °c ± 2°c One year ( Equivalent to R.T) 40 °c ± 2°c Six months CENTRIFUGATION One or two hours. Freeze/ thaw Cycle repeatedly between 4 °c and 40 °c or 45 °c . LIGHT TESTING Fluorescent One to two weeks ( or longer). Xenon One to two weeks. Ultraviolet One to two weeks. Daylight One year.
PILOT SCALEUP OF COSMETIC PILOT SCALEUP OF COSMETIC FORMULATIONS FORMULATIONS n It is not unusual for a formula which has been n Process Scale-up involves: successfully developed in the R&D lab to exhibit diﬀerent characteristics when it is transferred to n The successful duplication of a formulation’s primary production. As the formula is transferred from a small, physical characteristics over a speciﬁc range of laboratory-scale apparatus to large-scale production increasing batch sizes. equipment, a diﬀerence in condition is experienced.
GOALS OF SCALE-UP n The successful duplication of a formulation’s primary physical characteristics over a variety of manufacturing equipment. n Batch Reproducibility n Upon successful scale-up you can trouble shoot:
n n Manufacturing issues Quick startup in manufacturing.
n Formulation issues n Increased proﬁt to company.
n Equipment issues
n Raw material issues
REASONS FOR SCALE-UP n NEW REASONS:
TRADITIONAL REASONS: n Lower emulsiﬁer levels
n Requires higher mechanical energy
n Right ﬁrst time production batches n Better designed equipment with $ savings.
n Quicker to market for company Scale-up technique involves R&D pilot batches which require time and patience on the part of the formulator.
n Less downtime
WHAT IS THE RATIONALE FOR PILOT EQUIPMENT? n Useful for stability test data analysis in tandem with that n For preparation of scaled-up versions of speciﬁc R&D which is obtained from laboratory batches formulations intermediate in size between laboratory ( 1-2 kg) and production ( 1000-2000 gallon) batches. n Additionally, equipment can be utilized for small-sized production batches which could not be manufactured n Applicable for the following product types: utilizing normal processing kettles. n Emulsions including creams and lotions
n Suspensoid systems including gels and sticks.
n Non-Suspensoid systems and miscellaneous product types.
MANUFACTURING IN THE PLANT n In summary the overall beneﬁts of formulation scale-up in the cosmetic industry are as follows: ENVIRONMENT
n Provides a smoother transition of manufacturing procedures from the laboratory to the plant environment. n In our previous discussion of scale-up we examined the overall reasons and beneﬁts for pilot batches and n One can obtain fewer failures on ﬁrst-time procedures as they relate to cosmetic formulations. production batches.
n From an eﬃciency perspective, one can realize a quick production start-up with less scrap and n It is generally believed that scale-up is am engineering rework. function. In essence, it is a dual function between the formulator and the process team in the plant.
n Without going into detailed engineering equations n As the given formulation is guided through the scale-up regarding mixing criteria the key points to consider in the stages for plant production there are number of key areas plant setting for this procedure are that become critical to the overall process: n Impeller dimensions and types n Impeller speed n Mixing n Impeller diameter to tank diameter referred to as the O/T ratio. n Heat transfer n Turnover rate ( number of batch turnovers per unit time) n Mass transfer n Flow proﬁle based on the impeller and vessel conﬁguration and batch loading.
PROCESS ROBUSTNESS n Heat transfer variables primarily involve:
n Heat transfer medium n Within the pharmaceutical industry there is a term that is n Heating and cooling rates used which can be transferred to personal care manufacturing. That term is called PROCESS ROBUSTINESS. n Maximum and minimum temperatures
n ROBUSTINESS is deﬁned as “ the ability of a manufacturing n Lastly, mass transfer primarily is concerned with phase process to tolerate the expected variation of raw materials, transfer rates. operating conditions, process equipment, environmental conditions and human factors.” n It is important to understand that not all products react adversely with bench-to-production variations. There are n In order to develop a robust manufacturing process there many products robust enough to withstand all but the are six steps which need to be followed: most extreme variation.
n Team formation n Deﬁne the process n Prioritize experiments
RHEOLOGICAL CONSIDERATIONS AND n Analyze measurement capability n Identify functional relationships BATCH PROCESSING n Conﬁrm critical quality attributes and critical process n Deﬁnition of basic concepts: parameters.
n n Creating a system that facilitates increased process Rheology- Study of the ﬂow of matter. understanding and leads to process robustness beneﬁts n Viscosity- The measure of the matter’s the manufacturer through quality improvements and resistance to the ﬂow. cost reduction. n Rate of shear- The measure of movement of matter depending on force applied. n Information about the process setting and key n Viscosity= Shear stress/ rate of shear relationships are communicated to manufacturing. Upon transfer, manufacturing begins to verify R&D’s information on process robustness through process monitoring and data analysis. Both general and process speciﬁc improvement activities help manufacturing attain and maintain its goals.
PROCESSING PARAMETERS AND n Emulsions are systems where the viscosity varies with the rate of shear. This is in contrast with typical PROBLEMS Newtonian systems where viscosity is independent of n FACTORS INFLUENCING VISCOSITY the rate of shear.
1. Temperature of various processing steps n Emulsions can also exhibit:
n Individual phases before emulsiﬁcation
n Thixotropic properties- viscosity decreases with shear time. n Phases upon combination
n Cooling water temperature n Rheopectic properties- viscosity is a function of duration of the applied stress; viscosity increases n Blend pumped out of process vessel. with shear time ( rare in emulsion systems).
n Blend at ﬁlling point.
n 32 3/7/13
2. Mechanical work MIXING EQUIPMENT AND IMPLICATIONS
n Shear of mixing n n Homogenization or milling Extremely critical parameter for emulsion systems. n Transfer work ( pipes, values, nozzles, etc) 4. Time factors n In a highly thixotropic emulsion with a high yield value, n Heating period avoid a small propeller as only a small portion of ﬂuid n Cooling period near the propeller would move. A larger diameter n Mixing period propeller ( paddle type) would ensure for better mixing.
n All factors do not operate independent of each other. Ex-reducing mixing speed to minimize shear thinning results in decreased cooling eﬃciency. n Flow to ﬂuid shear ratio is the term used in engineering to judge mixing requirements.
EFFECTS OF VISCOSITY ON PROCESSING CONDITIONS
n In an emulsiﬁcation process, a high shear level ( high speed mixer) is needed, while in heat transfer steps, n Product viscosity can directly inﬂuence the mixing and such as heating and cooling, high ﬂow ( low speed cooling rate. mixer) is desirable. n In a high viscosity emulsion, the heat transfer eﬃciency is lower and, therefore, so is the rate of cooling. n Similarly, a high viscosity product or a shear thickening n A proper combination of the above two mixing procedures will yield the desired processing result. product can cause both pumping and ﬁlling problems under production conditions.
n AIR ENTRAPMENT is common in high viscosity products. This is dependent on : n Solutions for de-aeration include:
n n Amount of air “trapped” during processing and Gentle heating. ﬁlling. n Impeller size and / or speed adjustment.
n Amount of air escaping after entrapment. n Varying pumping procedure.
n A shear thinning system tends to aerate much easier than either Newtonian or shear thickening n Use of vacuum deaerator such as a versator. formulations
PUMPING VARIABLES DURING PROCESSING 1. SHARE POSITIVE DISPLACEMENT TYPE Diaphragm--- Good for liquid, low shear n Critical equipment for proper processing and ﬁlling of cosmetic type formulations. Gear--- Impart high shear Moyno--- Impart low to medium n Two basic types of pumps used for cosmetic processing: 2. Centrifugal type
Works on principle of conversion of contrifugal force into pressure. This type of pump will not function at very high pressure or viscosities.
COOLING CONDITIONS DURING PROCESSING PROCESS VALIDATION CONCEPTS
n DEFINITION- establishing documented evidence n This is critical in emulsions, as rate of cooling aﬀects the which provides a high degree of assurance that a ﬁnal viscosity. Some products require slow cooling, speciﬁc process will consistently produce a product “ ” while others require FORCED COOLING through use meeting pre-determined speciﬁcations and quality of a water jacket. attributes. n TWO BROAD TYPES OF VALIDATION n Temperature and seasonal factors can impact cooling Prospective--- That done for a new product or revised time in non-air-conditioned environments. Use of a manufacturing conditions. chiller may be essential.
Retrospective--- That done for a product already in n Similar in format to a total quality assurance standard operating procedure ( SOP) with special emphasis distribution. placed on particular areas such as :
n Fundamental concept is documentation of protocols n Gauge calibration and/or procedures so as to identify the “KEY” areas n Preventive maintenance which require special attention. n Statistical analysis
n Emphasis of process validation is on prevention which is identical with the concept of quality management.
PROCESS EQUIPMENT OVERVIEW