Micro/Nano Encapsulation

For more than 60 years, Southwest Research Institute (SwRI®) has been a leader in encapsulation research and development. Using their extensive expertise in diverse technical fields such as pharmaceuticals, food and nutrition, polymer and materials science, and process engineering, Institute encapsulation specialists solve product stability, release and application problems in a wide range of industries. The Institute has conducted more than 1,000 encapsulation research programs for commercial and govern­ment clients.

SwRI employs diverse encapsulation methods to solve product performance requirements for its clients. Encapsulation methods are broadly categorized as either physical or chemical.

Physical Methods

• Extrusion

  Particle size and morphology can be tailored to achieve the desired product performance.

• Fluidized bed
• Pan coating
• Atomization
  — Spinning disk
  — Spray drying
  — Spray chilling/congealing

Chemical Methods

• Solvent loss
• Phase separation
• Coacervation
• Polymerization
• Precipitation
• Nanoencapsulation
• Liposomes
• Sol-gel

SwRI’s Chemistry and Chemical Engineering Division, which houses the comprehensive encapsulation program, has achieved certification to ISO 9001:2000, ensuring compliance with stringent quality control procedures in development, production and testing. The en­capsulation program maintains numerous facilities, including current Good Manufacturing Practices (cGMP) suites.

Atomization

SwRI practices several atomization processes, includ­ing spinning disk, spray drying and spray congealing.

cGMP pilot-scale facilities are available for sample preparation. Custom encapsulation equipment is often fabricated to meet unique client demands.

Spinning disk is a highly versatile encapsulation process used to prepare matrix morphology and overcoated particles. SwRI per­sonnel have innovated the disk process to yield narrow particle size distributions, produce micron-sized particles, and process batch sizes down to a few grams with high recovery efficiency.

Applications

• Hot melts, prilling and congealing
• Solvent evaporation
• Water evaporation
• High-solids and high-viscosity feedstocks

Characteristics

• Particle sizes from 5 µm to 3,000 µm
• Narrow particle size distributions
• Feedstock versatility
• Scalability and high production capacity
• High recovery efficiency
• Continuous production

Spray drying is a traditional atomization process suitable for many feedstocks. Atomization is achieved by nozzle or veined wheels, two-fluid spray nozzles, pressure nozzles or sonic energy.

Spray drying can be used for

• Water- or solvent-based materials
• Temperature sensitive materials

	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

SwRI has developed and practices several particle and fiber extrusion techniques, including stationary nozzle, centrifugal extrusion, vibrating nozzle, submerged nozzle, electrohydrodynamics, single or twin-screw extrusion and microextrusion.

Vibrating nozzle systems produce microcapsules or microspheres with a very narrow size distribution.

Extrusion processes produce matrix or core-shell morphologies, depending on nozzle configuration. Particle extrusion processes produce narrowly distributed particles. SwRI scientists have in­novated particle extrusion processes to produce capsules down to sub-micron sizes with small particle size variances, operate with complex thermal profiles, and support production capac­ity. Fiber extrusion processes produce single or multiple fibers 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.

Applications

• Narrow size distributions
• Core-shell morphologies

  Stationary and submerged nozzles produce capsules of oils or aqueous fill materials using waxes or hydrophilic and lipophilic polymers.

• Gas, liquid or solid cores
• Variable shell thickness
• Variable payload composition

Characteristics

• Sizes from1 µm to 10,000 µm
• Narrow size distribution
• Material versatility
• Scalability and high production capacity
• Continuous production

These oil-filled microcapsules were produced with centrifugal coextrusion.

Nanoencapsulation

SwRI works extensively with many nanoencapsulation techniques to produce nanosized particles and capsules to address the high performance needs of many applica­tions. Nanocapsules can be used in combina­tion with other microencapsulation methods to provide new release characteristics.

SwRI personnel routinely use the following nanoencapsulation techniques:

SwRI scientists developed bone-targeting nanocarriers that release their payload following attachment to the target site. Payload release may occur by natural nanocarrier degradation, application of external stimuli, administration of a complementary factor in schedule, or in response to local biochemical signals.

• Micelles
• Liposomes and polymersomes
• Phase inversion/precipitation
• Solvent evaporation
• Polyelectrolyte complexes
• Layer-by-layer deposition
• Controlled precipitation
• Surfactant-free particle formation
• Templating
• Molecular encapsulation

Applications

• Protein, DNA and RNA stabilization
• Small molecule delivery
• Extending circulatory half-life
• Modifying drug transport
• Clear liquid formulations
• Stable colloid dispersions
• Controlled release
• Targeted delivery

  This scanning transmission electron micrograph shows silver nanoparticles encapsulated in a silica shell.

• Triggered release

Characteristics

• Particle sizes from 10nm
• Tunable colloid properties
• Chemically functional surfaces
• Hydrophobic or hydrophilic payloads
• Low payloads
• Organic or inorganic compositions
• High surface area particles

Chemical Techniques

Chemical encapsulation techniques typically yield particle dispersions that can be used as is or post-processed by other methods, such as spin­ning disk, spray drying or fluid bed to produce free-flowing powders.

Using the SwRI pilot plant equipment and 200-liter reactors, Institute chemists produce microspheres and synthesize kilogram batches of pharmaceuticals for phase one clinical trials.

Applications

• Oil-in-water emulsions
• Water-in-oil emulsions
• Core-shell capsules or matrix particles
• Stable, high-solid dispersions

Characteristics

• Particle sizes from about 0.1 µm to 500 µm
• High payloads
• Uniform particle size distribution
• Scalability and high production capacity
• Batch production

SwRI has developed and practices several chemical techniques, including:

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

	SwRI scientists have developed a novel core material for fluorescent monitoring of microcapsule oxidation.
The Institute employs a number of chemical methods­­­ to develop highly stable microcapsules as small as 0.1 µm.

Process Comparisons

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

SwRI scientists, with collaborative support from clients, evaluate and balance a variety of performance and formulation criteria when selecting the appropriate encapsulation process to meet customer objectives.

Process Selection Criteria

• Core/shell material properties
  — Gas/liquid/solid
  — Solubility
  — Viscosity/surface tension
  — Density
  — Reactivity
• Capsule size
• Capsule percent payload
• Capsule morphology
• Production capacity
• Release profile/mechanism
• Stability

  Top: Encapsulated, Bottom: Non-encapsulated. The use of microencapsulation technology provides increased retention of the active ingredient at the site of tumor injection resulting in reduced exposure to healthy tissue.

Pharmaceuticals

Applications

• Oral
• Injectibles
• Nasal
• Ocular
• Otic
• Transdermal

Features

• Targeted delivery
• Lower dose requirements
• Fewer systemic side effects
• Improved bioavailability
• Taste masking
• Improve drug stability
• Alternative formulations
• Potent drug
• Controlled substances

Food and Nutraceuticals

Institute facilities include a Good Manufacturing Practices-compliant laboratory for encapsulation studies related to the food and drug industries.

Applications

• Functional foods
• Taste masking
• Color masking
• Flavor stabilization
• Oxidation stability

Features

• Improved shelf life
• Formulation compatibility
• Liquid to solid

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.

Consumer and Diversified Products

With more than 60 years experience, SwRI provides microencapsulation solutions by offering a variety of controlled release mechanisms to the consumer and diversified products industries. Examples include detergents, cosmetics, deodorants and textiles.

Applications

• Cosmetics and cosmeceuticals
• Personal care
• Pet care
• Household products
• Toys and novelty items

Features

• Improved shelf life
• Formulation compatibility
• Liquid to solid

Agricultural and Industrial

Applications

• Pesticides, fungicides and fumigants
• Animal feeds, seeds
• Veterinary formulations

  SwRI has completed numerous projects related to the encapsulation of mosquito attractants, repellants and larvicides.

• Paints and coatings
• Catalysts, resins, adhesives
• Pigments, dyes, colorants
• Lubricants and additives
• Scratch and sniff
• Anti-counterfeiting
• Print advertising
• Inks

SwRI scientists develop encapsulated products for agricultural applications such as sustained release of pesticides and fertilizers, stabilization and increased bioavailability of animal feed nutrients and seed protection.

Release Mechanisms

SwRI develops particle and capsule formulations to achieve one or more release mechanisms to meet product performance requirements. SwRI routinely fine-tunes formulations and particle properties to tailor release rate and/or release profile.

Mechanically ruptured microcapsules are used to manufacture paper products such as scratch and sniff items and carbonless copy paper.

Common Controlled Release Profiles

• Triggered release – Release occurs due to a change in environment, such as pH, temperature, moisture, pressure, electromagnetic. This is used to achieve immediate, delayed or pulsatile release profiles.
• Sustained release – Release occurs for an extended period of time. This can be used to achieve constant active ingredient exposure for a fixed period.
• Burst release
• Combination release profiles

Release Mechanisms

• Diffusion
• Dissolution
• Molecular trigger (such as pH)
• Biodegradation

  Osmotic release is triggered by the absorption of water into the microcapsule core. Subsequent swelling ruptures the microcapsule shell.

• Thermal
• Mechanical
• Osmotic

Particle size is one of many parameters that may be adjusted to control release rates of encapsulated ingredients.

Product Characterization

SwRI uses a variety of analytical and physical meth­ods to characterize particles and encapsulated ingredients. SwRI routinely determines particle size, payload, content uniformity and stability, active in­gredient release profiles and activity, colloid stability and particle stability.

SwRI scientists use top-of-the-line molecular modeling systems for applying computational methods in pharmaceutical development to better understand protein and ligand interactions and new compound designs.

Particles

• Sizing down to 3 nm
• Powders
• Dispersions (aqueous and organics)
• Zeta potential

Particle Morphology

• Atomic force
• SEM/EDX
• Environmental SEM/STEM
• Optical microscopy

Thermal Analysis

• Differential scanning calorimetry
• Thermal gravimetric analysis
• Dynamic mechanical analysis

Rheology

Using an environmental scanning electron microscope, SwRI scientists are able to image nonconductive samples without extensive sample preparation.

• Low viscosity fluids, gelation and curing profiles, reinforced solid mechanical properties
• Large dynamic shear range, sub-ambient to >600°C temperature range
• Multiple frequency waveform generation

Payload

• HPLC
• IC, GC, GC/MS
• Fluorescent
• Thermal gravimetric analysis

Release

• Dissolution (pH, solvent)
• Thermal
• Pressure
• Simulated body fluids

  ESEM images of the SwRI MEMS logo.

• Cell culture
• Tissue culture

Stability

• Controlled environment (such as time, temperature, relative humidity, ultraviolet, acoustic)
• Simulated fluids
• Thermal and pressure
• Byproducts

Specialized

• Biological Safety Laboratory (BSL) 2-4
• Good Laboratory Practices (GLP)

For more information on microencapsulation and controlled release, see our department web page at microencapsulation.swri.org.
 

This brochure was published in July 2008. For more information on microencapsulation, contact Joe Persyn, Phone (210) 522-2691, James Oxley, Phone (210) 522-2913, Fax (210) 522-4565, Chemistry and Chemical Engineering Division, Southwest Research Institute, P.O. Drawer 28510, San Antonio, Texas 78228-0510, Fax (210) 522-4632.

Chemistry and Chemical Engineering Brochures SwRI Brochures
SwRI Publications SwRI Technical Divisions SwRI Home