MicroencapsulationAs a process, it is a means of applyingrelatively thin coatings to small particlesof solids or droplets of liquids anddispersions.The uniqueness microencapsulation isof smallness of the coated particles andtheir subsequent adaptation to a widevariety of dosage forms and productapplication.
ApplicationsThe applications of microencapsulation well includes in the formulation of Sustain release medications Delayed release medications Taste masked chewable tablets Single layer tablet containing incompatible ingredients.
Coating material The selection of a specific coating material from a lengthy list of candidate material presents the following questions to be considered by the research pharmacist. What is the specific dosage or product requirement e.g. stabilization, reduced volatility or release characteristics etc.
Cont….. What coating material will satisfy the product objective and requirement. What microencapsulation method is best suited to accomplish the coated product objective?
Cont….. In-addition the coating material should be capable of forming a film that is cohesive with the core material, be chemically compatible and non reactive with the core material and provide desired coating properties such as stability.
A typical coating materials commonly used in the various microencapsulation method is as follows Water soluble polymers : - gelatin, starch, polyvinyl pyrolidone, carboxy methyl cellulose, methyl cellulose, hydroxyethylcellulose, polyvinylacetate. Water insoluble polymers :- ethylcellulose, polyethylene, polymethacrylate, cellulose nitrate. Waxes and lipids :- bees wax, carnauba wax, spermaceti. Enteric resin s : - shellac, cellulose acetate phathalate, zein, HPMC phathalate, Eudragit L&S, polyvinyl acetate phathate.
Methodology Microencapsulation methods that have been or are being adapted to pharmaceutical use include Air suspension also known as fluidized bed coating. Spray drying Pan coating Coacervation- phase separation Solvent evaporation.
Microencapsulation process Applicable Air suspension- Solids-35-5000 or more ( Size in micron) Spray drying- Solids and liquids-600 Pan Coating- Solids- 600-5000 or more Coacervation–Phase separation- Solids and liquids-2-5000 or more Solvent Evaporation- Solids and liquids- 2-5000 or more
Air suspension or fluidized bed coating it is also known as wurster process , consist of the dispersing of solid particulate core material in a coating chamber. The particles are suspending on an upward moving hot air stream (fluidization) and coating material usually a polymer solution is applied in the form of spray to the moving particles. The supporting air stream also serves to dry the product while it is being encapsulated.
Process variables that receive consideration for efficient encapsulation includes Melting point, solubility, friability, volatility of the core material. Coating material concentration. Nature of the vehicle Coating material application rate Air velocity for fluidization. Inlet air temperature.
Spray drying In practice, microencapsulation by spray drying is conducted by dispersing the core material in a coating solution, in which the coating polymer is dissolved and the core material is insoluble and then atomizing the mixture in to an air stream. The air is usually heated required to remove the solvent from the coating material thus forming a microencapsulated product.
SPRAY DRYER The equipment components of a standard spray drier include an air heater atomizer spray chamber blower and product collector.
Process variables includes Concentration of coating material. Nature of the vehicle. Concentration of the core. Feed rate. Inlet air temperature.
Pan coating The microencapsulation of relatively large particles greater than 600 microns in size by pan methods has become widespread in the pharmaceutical industry. The method involves the application of a coating composition to a moving bed of particles with the concurrent use of heated air to facilitate evaporation of the solvent.
STANDARD COATING PAN The standard coating pan consist of a circular metal pan usually stainless steel of 8 o 60 inch in diameter mounted on a stand and rotates on its horizontal axis by a motor. The coating solutions are applied by spraying the material on the rotating particulate bed.
Process variables includes Diameter and speed of rotation of the coating pan. In let air temperature. Concentration of coating material. Nature of the vehicle used for the preparation of coating solution. Spray rate.
Coacervation- Phase SeparationMicroencapsulation by coacervation phase separation processes consist of three steps carried out under continues agitation. Formation of three immiscible chemical phases Deposition of the coating Rigidization of the coating.
Step I Step I of the process is the formation of three immiscible chemical phases, a liquid manufacturing vehicle phase. Core material phase and a coating material phase. To form three phases, the core material is dispersed in a solution of the coating polymer, the solvent for the polymer being the liquid manufacturing vehicle phase.
Cont… The coating material phase, an immiscible polymer in a liquid phase is formed by utilization of one of the method s of phase separation coacervation i.e. by changing the temperature of the polymer solution, or by adding the salt, non solvent, or incompatible polymer.
Step II Step II of the process consists of depositing the liquid polymer coating upon the core material. this is one by controlled physical mixing of the coating material while in liquid and the core material in the manufacturing vehicle. Deposition of the liquid polymer coating around the core material occurs if the polymer is adsorbed at the interface between the core material and the liquid vehicle phase.
Step III Step III of the process involves rigidizating the coating.
Explanation Figure illustrates a general temperature- composition phase diagram for a binary system comprised of a polymer and a solvent. A system having an overall composition represented as point X , exist as a single phase, homogeneous solution at all points above the phase boundary i.e. FEG .
Cont…. As the temperature of the system decreased from point A along the arrowed line AEB , the phase boundary is crossed at point E , and the two phase region is entered.
Cont… The phase separation of the dissolved polymer occurs in the form of liquid droplets and if the core material is present in the system, under proper polymer concentration and temperature, and agitation conditions, the liquid polymer droplets deposit around the core particles thus forming microcapsules.
Cont….. The phase boundary curve indicates that the decreasing temperature, one phase becomes polymer poor (vehicle phase) and the second phase (coating material phase) becomes polymer rich. At point B the vehicle phase is pure solvent, at C coexisting phase and at D, concentrated polymer-solvent mixture.
The example illustrates the microencapsulation by temperature change. Ethyl cellulose is insoluble in cyclohexane at room temperature but is soluble at elevated temperature. Thus 2% solution of ethyl cellulose is prepared in cyclohexane by heating to the boiling point. The core material n-acetyl para amino phenol is dispersed in the solution with stirring in the ratio of 1:2( coat: core). Allow the mixture to cool with constant stirring, effects phase separation of ethyl cellulose and microencapsulation of the core material. Further cooling results in the solidification of the coating. The microencapsulated product is then collected by filtration or centrifugation.
Coacervation-phase separation by Incompatible polymer addition Phase Diagram
Cont….. The diagram illustrates a ternary system consisting of a solvent, and two polymers X and Y. if an insoluble core material is dispersed in a solution of polymer Y(at point A in the figure) and polymer X( incompatible polymer) is added to the system denoted by the arrow line, the phase boundary is crossed at point E. further addition of polymer X, liquid polymer i.e polymer Y will separated out as droplets and coating of microcapsules exist at point B.
Example Microencapsulation of methylene blue HCL with ethyl cellulose by this mode is described as follows:- Ethyl cellulose dissolve in toluene to yield polymer concentration of 2% by weight. The methylene blue HCL, being insoluble in toluene, is dispersed with stirring in a polymer solution at a ratio of 4 parts of methylene blue HCL to 1 pqrt of ethylcellulose.
Cont… Phase separation is done by slowly adding liquid polybutadiene. The polybutadiene being quite soluble in toluene and incompatible with ethylcellulose effects the separation of ethylcellulose from the polybutadiene toluene solution and subsequent microencapsulation of the dispersed core material. The microencapsulated product is then collected by filtration or centrifugation.
Solvent evaporation The microcapsule coating is dissolved in a volatile solvent which is immiscible with the liquid manufacturing vehicle phase. A core material to be microencapsulated is dispersed in the coating polymer solution with agitation. The mixture is then heated to evaporate the solvent for the polymer with continues agitation. Once all the solvent for the polymer is evaporated, the liquid temperature is reduce to ambient temperature. The microencapsulated product is then collected by filtration or centrifugation.
Process variables– Temperature for evaporation of polymer solvent– Agitation rate.