Encapsulation

MICROencapsulation

Southwest Research Institute, an independent, nonprofit applied engineering and physical sciences research and development NANO organization with 10 technical divisions, uses multidisciplinary approaches to problem solving. The Institute occupies more than 1,200 acres in San Antonio, Texas, and provides more than 2 million square feet of laboratories, test facilities, workshops and offices for nearly 3,000 employees who perform contract work for industry and government clients.

Benefiting government, industry and the public through innovative science and technology We welcome your inquiries. For additional information, please contact:

Joseph T. Persyn, Manager (210) 522-2691 • Fax (210) 522-4565 [email protected]

James D. Oxley, Ph.D., Principal Scientist (210) 522-2913 • Fax (210) 522-4565 [email protected]

Pharmaceuticals and Bioengineering Department Chemistry and Chemical Engineering Division Southwest Research Institute 6220 Culebra Road • P.O. Drawer 28510 San Antonio, Texas 78228-0510

microencapsulation.swri.org swri.org

® Quality System Quality Certification — Chemistry and Chemical Engineering Division Southwest Research Institute Registered to The Chemistry and Chemical Engineering Division of Southwest Research Institute has ISO 9001:2008 achieved certification to ISO 9001:2008, an internationally recognized quality standard. San Antonio, Texas SwRI Business Development • San Antonio, Texas • (210) 522-2122 • Fax (210) 522-3496 • E-mail [email protected] encapsulation Product Characterization

D019117-7084 or more than 60 years, Southwest Research Institute (SwRI®) has been a leader in SwRI uses a variety of analytical and physical meth- encapsulation research and development. Using their extensive expertise in diverse ods to characterize particles and encapsulated technical fields such as pharmaceuticals, food and nutrition, polymer and materials science, and process engineering, Institute encapsulation specialists solve product ingredients. SwRI routinely determines particle size, stability,F release and application problems in a wide range of industries. The Institute has payload, content uniformity and stability, active in- conducted more than 1,000 encapsulation research programs for commercial and govern- gredient release profiles and activity, colloid stability ment clients. and particle stability. SwRI employs diverse encapsulation methods to solve product performance requirements for its clients. Encapsulation methods are broadly categorized as either physical or chemical. Particles n Sizing down to 3 nm n Powders n Dispersions (aqueous and organics) n Zeta potential Southwest Physical Methods Chemical Methods Particle Morphology Research Institute n Extrusion n Solvent loss n Atomic force n Fluidized bed n Phase separation n SEM/EDX SwRI scientists use top-of-the-line molecular modeling systems Founded in 1947 as an inde- n Pan coating n Coacervation n Environmental SEM/STEM for applying computational methods in pharmaceutical development pendent, nonprofit research to better understand protein and ligand interactions and new n Optical microscopy and development organiza- n Atomization n Polymerization compound designs. tion, Southwest Research – Spinning disk n Precipitation Institute provides a significant – Spray drying n Nanoencapsulation Thermal Analysis n research, engineering and – Spray chilling/congealing n Liposomes Differential scanning calorimetry n testing resource for industry, n Sol-gel Thermal gravimetric analysis business and government. The n Dynamic mechanical analysis Institute uses a multidisciplinary, integrated approach to Rheology solving complex problems in n Low viscosity fluids, gelation and curing profiles, science and applied technol- SwRI’s Chemistry and Chemical Engineering Division, which houses the comprehensive reinforced solid mechanical properties ogy. As part of a long-held encapsulation program, has achieved certification to ISO 9001:2008, ensuring compliance n Large dynamic shear range, sub-ambient tradition, patent rights arising with stringent quality control procedures in development, production and testing. The en- to >600°C temperature range from sponsored research at capsulation program maintains numerous facilities, including current Good Manufacturing n Multiple frequency waveform generation the Institute are often assigned Practices (cGMP) suites. to the client. SwRI generally retains the rights to Institute- Payload funded advancements. n HPLC n IC, GC, GC/MS n Fluorescent Using an environmental scanning electron microscope, SwRI SwRI® maintains Controlled n Thermal gravimetric analysis scientists are able to image nonconductive samples without Substance Registrations extensive sample preparation. with the Drug Enforcement Release Administration permitting n Dissolution (pH, solvent) the Institute to handle n controlled substances for Thermal the business activity of n Pressure research and manufacturing. n Simulated body fluids n Cell culture ESEM images of the n Tissue culture SwRI MEMS logo. ©2015 Southwest Research Institute. All rights reserved. Stability n Controlled environment (such as time, temperature, Southwest Research Institute and relative humidity, ultraviolet, acoustic) SwRI are registered trademarks in the n Simulated fluids U.S. Patent and Trademark Office. n Thermal and pressure Particle size and morphology can be tailored to achieve the desired product performance. n Byproducts An Equal Employment Opportunity/ Affirmative Action Employer Race/Color/Religion/Sex/Sexual Orientation/ Specialized Gender Identity/National Origin/Disabled/Veteran n Biological Safety Laboratory (BSL) 2-4 Committed to Diversity in the Workplace n Good Laboratory Practices (GLP) Release Mechanisms Atomization

SwRI develops particle and capsule formulations to SwRI practices several atomization processes, includ- achieve one or more release mechanisms to meet ing spinning disk, spray drying and spray congealing. product performance requirements. SwRI routinely Spinning disk is a highly versatile encapsulation process used to fine-tunes formulations and particle properties to prepare matrix morphology and overcoated particles. SwRI per- tailor release rate and/or release profile. sonnel have innovated the disk process to yield narrow particle size distributions, produce micron-sized particles, and process Common Controlled Release Profiles batch sizes down to a few grams with high recovery efficiency. n Triggered release – Release occurs due to a change in Applications environment, such as pH, temperature, moisture, pressure, n Hot melts, prilling and congealing electromagnetic. This is used to achieve immediate, n Solvent evaporation delayed or pulsatile release profiles. n Water evaporation n Sustained release – Release occurs for an extended n High-solids and high-viscosity feedstocks period of time. This can be used to achieve constant active ingredient exposure for a fixed period. Mechanically ruptured microcapsules are used to manufacture Characteristics n Burst release paper products such as scratch and sniff items and carbonless copy paper. n Combination release profiles n Particle sizes from 5 μm to 3,000 μm n Narrow particle size distributions n Feedstock versatility Release Mechanisms n Scalability and high production capacity n High recovery efficiency n Diffusion n Continuous production n Dissolution n Molecular trigger (such as pH) Spray drying is a traditional atomization process suitable for many n Biodegradation Osmotic release is triggered feedstocks. Atomization is achieved by nozzle or veined wheels, by the absorption of water n two-fluid spray nozzles, pressure nozzles or sonic energy. Thermal into the microcapsule core. n Mechanical Subsequent swelling ruptures n Osmotic the microcapsule shell. Spray drying can be used for cGMP pilot-scale facilities are available for sample n Water- or solvent-based materials preparation. Custom encapsulation equipment is often fabricated to meet unique client demands. n Temperature sensitive materials

Particle size is one of many parameters that may be adjusted to control release rates of encapsulated ingredients. SwRI scientists utilized a spray-chilling process to prepare these microspheres.

An SwRI-developed spinning disk provides spherical particles with uniform coating and narrow particle size distributions. Extrusion Consumer and Diversified Products

Applications SwRI has developed and practices several particle n Cosmetics and cosmeceuticals and fiber extrusion techniques, including station- n Personal care ary nozzle, centrifugal extrusion, vibrating nozzle, n Pet care submerged nozzle, electrohydrodynamics, single or n Household products n twin-screw extrusion and microextrusion. Toys and novelty items Features Extrusion processes produce matrix or core-shell morphologies, depending on nozzle configuration. Particle extrusion processes n Improved shelf life produce narrowly distributed particles. SwRI scientists have in- n Formulation compatibility novated particle extrusion processes to produce capsules down n Liquid to solid to sub-micron sizes with small particle size variances, operate with complex thermal profiles, and support production capac- Vibrating nozzle systems produce microcapsules or ity. Fiber extrusion processes produce single or multiple fibers microspheres with a very narrow size distribution. with diameters down to several hundred nanometers. SwRI personnel have devised fiber extrusion processes to produce matrix fibers, core-shell fibers, and multilayer, fibrous structures. With more than 60 years experience, SwRI Applications provides microencapsulation solutions by offering a variety of controlled release n Narrow size distributions mechanisms to the consumer and diversified n Core-shell morphologies products industries. Examples include n Gas, liquid or solid cores detergents, cosmetics, deodorants and textiles. n Variable shell thickness n Variable payload composition Characteristics n Sizes from1 μm to 10,000 μm n Narrow size distribution Agricultural and Industrial n Material versatility n Scalability and high production capacity Applications n Continuous production n Pesticides, fungicides and fumigants n Animal feeds, seeds n Veterinary formulations n Paints and coatings n Catalysts, resins, adhesives n Pigments, dyes, colorants n Lubricants and additives n Scratch and sniff n Anti-counterfeiting n Print advertising n Inks

Stationary and submerged nozzles produce capsules of oils or aqueous fill SwRI scientists develop encapsulated products for agricultural materials using waxes or applications such as sustained release of pesticides and fertilizers, hydrophilic and lipophilic stabilization and increased bioavailability of animal feed nutrients polymers. and seed protection.

SwRI has completed numerous projects related to the encapsulation of mosquito These oil-filled microcapsules were attractants, repellants and larvicides. produced with centrifugal coextrusion. Pharmaceuticals Nanoencapsulation Applications Encapsulated SwRI works extensively with many n Oral n Injectibles nanoencapsulation techniques to produce n Nasal nanosized particles and capsules to address n Ocular the high performance needs of many applica- n Otic tions. Nanocapsules can be used in combina- n Transdermal Non-encapsulated tion with other microencapsulation methods Features to provide new release characteristics. n Targeted delivery SwRI personnel routinely use the following n Lower dose requirements nanoencapsulation techniques: n Fewer systemic side effects n Improved bioavailability n Micelles n Taste masking n Liposomes and polymersomes n Improve drug stability n Phase inversion/precipitation n SwRI scientists developed bone-targeting nanocarriers that release their Alternative formulations n Solvent evaporation payload following attachment to the target site. Payload release may n Potent drug n Polyelectrolyte complexes occur by natural nanocarrier degradation, application of external stimuli, n Controlled substances SwRI offers a broad spectrum of n Layer-by-layer deposition administration of a complementary factor in schedule, or in response to local biochemical signals. services to the pharmaceutical n Controlled precipitation industries, including drug The use of discovery, drug synthesis, drug n Surfactant-free particle formation microencapsulation technology delivery, modeling, method n Templating provides increased retention of the active development, and analytical and n ingredient at the site of tumor injection resulting Molecular encapsulation bioanalytical testing. All services in reduced exposure to healthy tissue. are performed under Good Laboratory Practices. Applications n Protein, DNA and RNA stabilization n Small molecule delivery n Extending circulatory half-life Food and Nutraceuticals n Modifying drug transport n Clear liquid formulations Applications n Stable colloid dispersions n Functional foods n Controlled release n Taste masking Institute facilities include a Good Manufacturing n Targeted delivery Practices-compliant laboratory for encapsulation n Triggered release n Color masking studies related to the food and drug industries. n Flavor stabilization n Oxidation stability Characteristics This scanning transmission electron micrograph shows silver nanoparticles encapsulated in a silica shell. n Particle sizes from 10nm Features n Tunable colloid properties n Improved shelf life n Chemically functional surfaces n Formulation compatibility n Hydrophobic or hydrophilic payloads n Liquid to solid n Low payloads n Organic or inorganic compositions n High surface area particles

A variety of nanoencapsulation techniques are practiced at SwRI to match the growing demand for these technologies. Microencapsulation is crucial for the nutraceutical market in developing health foods that taste good. SwRI encapsulation improves the shelf life and stability of nutritional supplements and can even mask the taste of fish oil, a nutritional supplement. Chemical Techniques Process Comparisons

Chemical encapsulation techniques typically SwRI scientists, with yield particle dispersions that can be used as is or collaborative support from post-processed by other methods, such as spin- clients, evaluate and balance ning disk, spray drying or fluid bed to produce a variety of performance and free-flowing powders. formulation criteria when selecting the appropriate Applications encapsulation process to n Oil-in-water emulsions meet customer objectives. n Water-in-oil emulsions n Core-shell capsules or matrix particles Process Selection Criteria n Stable, high-solid dispersions n Core/shell material properties – Gas/liquid/solid Characteristics Using the SwRI pilot plant – Solubility n equipment and 200-liter Particle sizes from about 0.1 μm to 500 μm reactors, Institute chemists – Viscosity/surface tension n High payloads produce microspheres – Density n Uniform particle size distribution and synthesize – Reactivity n Scalability and high production capacity kilogram batches of n Capsule size n pharmaceuticals for n Capsule percent payload Batch production phase one clinical trials. n Capsule morphology SwRI has developed and n Production capacity practices several chemical n Release profile/mechanism Microcapsule size is highly dependent on the process. The above graph illustrates general guidelines. techniques, including: n Stability

n Solvent evaporation n In situ polymerization n Interfacial polymerization n Emulsion polymerization n Simple and complex coacervation n Layer-by-layer deposition n Liposomes

Layer-by-layer deposition adds new properties and stability to existing shell systems.

Encapsulation processes offer different levels of complexity, capacity and operating cost with relative comparisons shown in the accompanying graph.

n Solvent evaporation n In situ polymerization n Interfacial polymerization n Emulsion polymerization n Simple and complex coacervation n Layer-by-layer deposition n Liposomes

Layer-by-layer deposition adds new properties and stability to existing shell systems.

Encapsulation processes offer different levels of complexity, capacity and operating cost with relative comparisons shown in the accompanying graph.

SwRI scientists have developed a novel core material for The Institute employs a number of chemical methods to develop fluorescent monitoring of microcapsule oxidation. highly stable microcapsules as small as 0.1 μm. Pharmaceuticals Nanoencapsulation Applications Encapsulated SwRI works extensively with many n Oral n Injectibles nanoencapsulation techniques to produce n Nasal nanosized particles and capsules to address n Ocular the high performance needs of many applica- n Otic tions. Nanocapsules can be used in combina- n Transdermal Non-encapsulated tion with other microencapsulation methods Features to provide new release characteristics. n Targeted delivery SwRI personnel routinely use the following n Lower dose requirements nanoencapsulation techniques: n Fewer systemic side effects n Improved bioavailability n Micelles n Taste masking n Liposomes and polymersomes n Improve drug stability n Phase inversion/precipitation n SwRI scientists developed bone-targeting nanocarriers that release their Alternative formulations n Solvent evaporation payload following attachment to the target site. Payload release may n Potent drug n Polyelectrolyte complexes occur by natural nanocarrier degradation, application of external stimuli, n Controlled substances SwRI offers a broad spectrum of n Layer-by-layer deposition administration of a complementary factor in schedule, or in response to local biochemical signals. services to the pharmaceutical n Controlled precipitation industries, including drug The use of discovery, drug synthesis, drug n Surfactant-free particle formation microencapsulation technology delivery, modeling, method n Templating provides increased retention of the active development, and analytical and n ingredient at the site of tumor injection resulting Molecular encapsulation bioanalytical testing. All services in reduced exposure to healthy tissue. are performed under Good Laboratory Practices. Applications n Protein, DNA and RNA stabilization n Small molecule delivery n Extending circulatory half-life Food and Nutraceuticals n Modifying drug transport n Clear liquid formulations Applications n Stable colloid dispersions n Functional foods n Controlled release n Taste masking Institute facilities include a Good Manufacturing n Targeted delivery Practices-compliant laboratory for encapsulation n Triggered release n Color masking studies related to the food and drug industries. n Flavor stabilization n Oxidation stability Characteristics This scanning transmission electron micrograph shows silver nanoparticles encapsulated in a silica shell. n Particle sizes from 10nm Features n Tunable colloid properties n Improved shelf life n Chemically functional surfaces n Formulation compatibility n Hydrophobic or hydrophilic payloads n Liquid to solid n Low payloads n Organic or inorganic compositions n High surface area particles

Particle size is one of many parameters that may be adjusted to control release rates of encapsulated ingredients. SwRI scientists utilized a spray-chilling process to prepare these microspheres.

An SwRI-developed spinning disk provides spherical particles with uniform coating and narrow particle size distributions. encapsulation Product Characterization

Benefiting government, industry and the public through innovative science and technology We welcome your inquiries. For additional information, please contact:

Joseph T. Persyn, Manager (210) 522-2691 • Fax (210) 522-4565 [email protected]

James D. Oxley, Ph.D., Principal Scientist (210) 522-2913 • Fax (210) 522-4565 [email protected]

Pharmaceuticals and Bioengineering Department Chemistry and Chemical Engineering Division Southwest Research Institute 6220 Culebra Road • P.O. Drawer 28510 San Antonio, Texas 78228-0510

microencapsulation.swri.org swri.org