Slide 1: AMIT M. GUPTA
AGNIHOTRI COLLEGE OF PHARMACY, WARDHA Micro-encapsulation : Micro-encapsulation Micro-encapsulation is a process in which tiny particles or droplets are surrounded by a coating to give small capsules.
In a relatively simplistic form, a microcapsule is a small sphere with a uniform wall around it.
The material inside the microcapsule is referred to as the core, internal phase, or fill, whereas the wall is sometimes called a shell, coating, or membrane.
Most microcapsules have diameters between a few micrometers and a few millimeters. Slide 3: The definition has been expanded, and includes most foods. Every class of food ingredient has been encapsulated; flavors are the most common. The technique of microencapsulation depends on the physical and chemical properties of the material to be encapsulated.
Many microcapsules however bear little resemblance to these simple spheres. The core may be a crystal, a jagged adsorbent particle, an emulsion, a suspension of solids, or a suspension of smaller microcapsules. The microcapsule even may have multiple walls Reasons for encapsulation : Reasons for encapsulation The reasons for microencapsulation are countless. In some cases, the core must be isolated from its surroundings, as in isolating vitamins from the deteriorating effects of oxygen, retarding evaporation of a volatile core, improving the handling properties of a sticky material, or isolating a reactive core from chemical attack. In other cases, the objective is not to isolate the core completely but to control the rate at which it leaves the microcapsule, as in the controlled release of drugs or pesticides. The problem may be as simple as masking the taste or odor of the core, or as complex as increasing the selectivity of an adsorption or extraction process. Slide 5: Application of Microencapsulation Slide 6: Application of microencapsulation
Actually about any area in the industry could beneficiate from microencapsulation technologies. Microencapsulation can be found in :
- Cell immobilisation :
In plant cell cultures microencapsulation, by mimicking cell natural environment, improves efficiency in production of different metabolites used for medical, pharmacological and cosmetic purposes.
Human tissue are turned into bio-artificial organs by encapsulation in natural polymers and transplanted to control hormone-deficient diseases such as diabetes and severe cases of hepatic failure.
In continuous fermentation processes immobilisation is used to increase cell density, productivity and to avoid washout of the biological catalysts from the reactor. This has already been applied in ethanol and solvent production, sugar conversion or wastewater treatment.
Beverage production : Today beer, wine, vinegar and other food drinks production are using immobilisation technologies to boost yield, improve quality, change aromas, etc...
- Protection of molecules from other compounds : Microencapsulation is often a necessity to solve simple problem like the difficulty to handle chemicals (detergents dangerous if directly exposed to human skin) as well as many other molecule inactive or incompatible if mixed in any formulation. Moreover, microencapsulation allows also to prepare many formulation with lower chemical loads reducing significantly processes’ cost. Slide 7: - Drug delivery : After designing the right biodegradable polymers, microencapsulation has permitted controlled release delivery systems. These revolutionary systems allow controlling the rate, duration and distribution of the active drug. With these systems, microparticles sensitive to the biological environment are designed to deliver an active drug in a site-specific way (stomach, colon, specific organs). One of the main advantages of such systems is to protect sensitive drug from drastic environment (pH, ...) and to reduce the number of drug administrations for patient.
- Quality and safety in food, agricultural & environmental sectors : Development of the “biosensors” has been enhanced by encapsulated bio-systems used to control environmental pollution, food cold chain (abnormal temperature change)...
- Soil inoculation : For example Rhizobium is a very interesting bacteria whichimproves nitrate adsorption and conversion. But inoculation is often unsuccessful because cells are washed out by rain. By cell encapsulation processes, it is possible to maintain continuous inoculation and higher cell concentration.
This list is not exhaustive, the nutraceuticals’ world could be the last mentioned because of the growing interest & increasing demand we have to face in ingredients with health benefits which often require improvement of their efficiency and stability (e.g. probiotics, vitamins...) by protecting and offering targeting release of the active materials. Microencapsulation Technologies : Microencapsulation Technologies Physical Methods of Encapsulation
Rotary disk atomization
Fluid bed coating
Stationary nozzle coextrusion
Centrifugal head coextrusion
Submerged nozzle coextrusion
Pan coating Chemical Methods of Encapsulation
Simple and complex coacervation
Nanoencapsulation Techniques to manufacture microcapsules : Techniques to manufacture microcapsules Physical methods
The pan coating process, widely used in the pharmaceutical industry, is among the oldest industrial procedures for forming small, coated particles or tablets. The particles are tumbled in a pan or other device while the coating material is applied slowly. Slide 10: Air-suspension coating
Air-suspension coating of particles by solutions or melts gives better control and flexibility. The particles are coated while suspended in an upward-moving air stream. They are supported by a perforated plate having different patterns of holes inside and outside a cylindrical insert. Just sufficient air is permitted to rise through the outer annular space to fluidize the settling particles. Most of the rising air (usually heated) flows inside the cylinder, causing the particles to rise rapidly. At the top, as the air stream diverges and slows, they settle back onto the outer bed and move downward to repeat the cycle. The particles pass through the inner cylinder many times in a few minutes. Slide 12: Fluidization is a process similar to liquefaction whereby a granular material is converted from a static solid-like state to a dynamic fluid-like state. This process occurs when a fluid (liquid or gas) is passed up through the granular material.
When a gas flow is introduced through the bottom of a bed of solid particles, it will move upwards through the bed via the empty spaces between the particles. At low gas velocities, aerodynamic drag on each particle is also low, and thus the bed remains in a fixed state. Increasing the velocity, the aerodynamic drag forces will begin to counteract the gravitational forces, causing the bed to expand in volume as the particles move away from each other. Further increasing the velocity, it will reach a critical value at which the upward drag forces will exactly equal the downward gravitational forces, causing the particles to become suspended within the fluid. At this critical value, the bed is said to be fluidized and will exhibit fluidic behavior. By further increasing gas velocity, the bulk density of the bed will continue to decrease, and its fluidization becomes more violent, until the particles no longer form a bed and are “conveyed” upwards by the gas flow. Slide 13: Centrifugal extrusion
Liquids are encapsulated using a rotating extrusion head containing concentric nozzles. In this process, a jet of core liquid is surrounded by a sheath of wall solution or melt. As the jet moves through the air it breaks, owing to Rayleigh instability, into droplets of core, each coated with the wall solution. While the droplets are in flight, a molten wall may be hardened or a solvent may be evaporated from the wall solution. Since most of the droplets are within ± 10% of the mean diameter, they land in a narrow ring around the spray nozzle. Hence, if needed, the capsules can be hardened after formation by catching them in a ring-shaped hardening bath.This process is excellent for forming particles 400–2,000 µm (16–79 mils) in diameter. Since the drops are formed by the breakup of a liquid jet, the process is only suitable for liquid or slurry. A high production rate can be achieved, i.e., up to 22.5 kg (50 lb) of microcapsules can be produced per nozzle per hour per head. Heads containing 16 nozzles are available. Slide 14: Vibrational Nozzle
Core-Shell encapsulation or Microgranulation (matrix-encapsulation) can be done using a laminar flow through a nozzle and an additional vibration of the nozzle or the liquid. The vibration has to be done in resonance of the Rayleigh instability and leads to very uniform droplets. The liquid can consists of any liquids with limited visocsities (0-10,000 mPa·s have been shown to work), e.g. solutions, emulsions, suspensions, melts etc. The soldification can be done according to the used gelation system with an internal gelation (e.g. sol-gel processing, melt) or an external (additional binder system, e.g. in a slurry). The process works very well for generating droplets between 100–5,000 µm (3.9–200 mils), applications for smaller and larger droplets are known. The units are deployed in industries and research mostly with capacities of 1–10,000 kg per hour (2–22,000 lb/h) at working temperatures of 20-1,500°C (68-2,700°F) (room temperature up to molten silicon). Nozzles heads are available from one up to several hundred thousand are available.
Spray drying serves as a microencapsulation technique when an active material is dissolved or suspended in a melt or polymer solution and becomes trapped in the dried particle. The main advantages is the ability to handle labile materials because of the short contact time in the dryer, in addition, the operation is economical. In modern spray dryers the viscosity of the solutions to be sprayed can be as high as 300 mPa·s. Slide 15: Set-up for
Size of microcapsules prepared is about 300-400 ?m Slide 16: Examples of Shell Materials
Natural and synthetic polymers
Resins Analytical Capabilities
Particle size analyzer
Optical and electron microscopes
D’Nouy ring or Wilhelmy plate tensiometer
Fourier transform infrared (FTIR)
Nuclear magnetic resonance (NMR) spectroscopy
High performance liquid chromatographs (HPLC)
Differential scanning calorimeter (DSC)
Thermogravimetric analyzer (TGA)
Gas chromatograph/mass spectrometer (GC/MS)
Ultraviolet-visible spectrophotometer Slide 17: Unique Release Mechanisms
Controlled, sustained, delayed, targeted release
Enteric, thermal, pressure, osmotic, pH-induced, pulsatile release
Biodegradable or salt-induced release
Oral, injectable, pulmonary, intranasal, implantable drug delivery Previously Encapsulated Materials : Previously Encapsulated Materials Acids
Animal feed ingredients
Inks Inorganic salts
Water Microencapsulation : Microencapsulation First studied in the food industry and in the development of carbonless paper
Use in drug delivery pioneered almost 40 years ago
Several systems developed for the encapsulation of different therapeutic agents as well as for encapsulation of cells
Variety of polymers used: Alginate, agarose, gellan gum, gelatin, chitosan, PLGA, polyvinyl alcohol, collagen, polyacrylamide
Various methods used: Emulsification, ionotropic gelation, thermal gelation, in situ polymerization, interfacial polymerization Microcapsules for Drug Delivery : Microcapsules for Drug Delivery Kinetics of drug release can be altered
Duration of release can varied over great periods of time
Surface modification can enable targeting to specific sites
Most methods of preparation utilize organic solvents
Aggregation of proteins and loss of protein activity has been reported
Sterilization of microcapsules also poses a problem
Water soluble polymers such as alginate present an attractive choice for protein delivery Choice of Polymer and Method of Microencapsulation : Choice of Polymer and Method of Microencapsulation The polymer should be
Not interact with the drug or protein
The microencapsulation method should be mild and should not involve the use of
Harsh solvents Slide 22: Release Mechanisms
Molecular trigger (such as pH)
Osmotic Slide 23: Amit M. Gupta
Agnihotri Collage of pharmacy, Wardha Thank you Micro-