Microencapsulation

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1. Microencapsulation Ravish Yadav

2. DEFNITION Microencapsulation is a mean of applying relatively thin coatings to small particle of solids or liquids and dispersions. Microencapsulation differ from macrocoating technique in the former involves coatings of particles ranging from several length of a micron to 5000 micron in size

3. Microencapsulation provide the mean of : Converting liquid to solids Altering colloidal and surface properties Providing environmental protection Controlling the release characteristics or availability of coated materials. Uniqueness of microencapsulation is the smallness of the coated particles and their subsequent use in variety of dosage forms.

4. Morphology of Microcapsules: The morphology of microcapsules depends mainly on the core material and the deposition process of the shell. 1- Mononuclear (core-shell) microcapsules contain the shell around the core. 2- Polynuclear capsules have many cores enclosed within the shell. 3- Matrix encapsulation in which the core material is distributed homogeneously into the shell material. In addition to these three basic morphologies, microcapsules can also be mononuclear with multiple shells, or they may form clusters of microcapsules.

5. Morphology of Microcapsules

6. Formulation Microspheres consist of two parts 1.core material 2.coating material Core material It is defined as the specific material to be coated can be liquid or solid in nature . The composition of core material can be varied This ability provide definite flexibility and utilization of this character allows effectual design and development of desired microcapsule properties.

7. Coating materials properties: Stabilization of core material. Inert toward active ingredients. Controlled release under specific conditions. Film-forming, pliable, tasteless, stable. Non-hygroscopic, no high viscosity, economical. Soluble in an aqueous media or solvent, or melting. The coating can be flexible, brittle, hard, thin etc.

8. Classification of coating material Water soluble resin Gelatin Gum Arabica PVP CMC MC Hydroxy ethyl -cellulose Water insoluble resin Ethyl cellulose Polyethylene Polyamide / nylon Polymethacrylate Cellulose nitrate -silicones Waxes and Lipids Paraffin Beewax Stearic acid Stearyl alcohol Glyceryl stearates Enteric resin Shellac Cellulose acetate- phthalate Zein

9. Microencapsulation Techniques 1) Air suspension 2) Coascervation /Phase separation 3) Multiorifice centrifugation 4)Pan coating 5) Spray coating 6) Solvent evaporation 7) Interfacial polymerization

10. Air suspension It is known as wurster process which consist of the dispersing of solid ,particulate core material in a supporting air stream and the spray coating of the air suspended particles with in a coating chamber particles are suspended on an upward moving air stream.

11. Fluidized-Bed Technology: - Different types of fluid-bed coaters include top spray, bottom spray, and tangential spray. - used for encapsulating solid or liquids absorbed into porous particles. Steps: 1-Solid particles to be encapsulated are suspended on a jet of air and then covered by a spray of liquid coating material. 2- The rapid evaporation of the solvent helps in the formation of an outer layer on the particles. 3- This process is continued until the desired thickness and weight is obtained.

12. Schematics of a fluid-bed coater. (a) Top spray; (b) bottom spray; (c) tangential spray

13. Coacervation –Phase separation Coacervation occurs in three stages 1)Formation of three immiscible chemical phase 2)Application of coating material 3) Rigidization of coating material 1)Formation of three immiscible chemical phase three immiscible phases are 1)coating material 2)core material 3)liquid manufacturing vehicle

14. Core material is dispersed in a solution of coating polymer The solvent for polymer being the liquid manufacturing vehicle phase Separation of coating material from manufacturing vehicle take place by one of the methods below a)Temperature changes E F G Temp polymer

15. It is a biphasic system –polymer and solvent phase diagram Above FEG polymer solution exists as homogeneous phase when temperature decreases it crosses phase boundary and polymer get separated from vehicle phase . Polymer coaservates around core particle and microencapsulation occurs Eg. Microencapsulation of acetaminophen using ethyl cellulose in cyclohexane solution

16. b)By adding incompatible polymer It involve a ternary system consisting of solvent and two polymer x and y .Polymer x is dissolved in vehicle core particle is dispersed in polymer x .To this incompactible polymer y is added . When concentration of polymer y increases it crosses the phase boundary and phase separation occur .polymer coacervates around core material resulting in microencapsulation. E 100% polymerY 100% polymerX

17. Eg. microencapsulation of methylene blue hydrocolloid using ethyl cellulose in toluene solution Incompatible polymer- polybutadiene c)By adding non-solvent to polymer A non solvent is added instead of incompatible polymer Eg; microencapsulation of methyl scopolamine using cellulose acetate butyrate Solvent-methyl ethyl ketone Nonsolvent -isopropyl ether

18. d) By adding salt soluble inorganic salt is added to aqueous solution of certain water soluble polymers to cause phase separation Eg; oil soluble vitamin microencapsulation induced by adding sodium sulphate to a gelatin solution Inorganic salt –sodium sulphate

19. e)Polymer-Polymer interaction The interaction of oppositely charged polyelectrolyte can result in the formation of a complex having such reduced solubility that phase separartion occurs eg ; polymer used are acacia (+ ve ) and gelatin (- ve )

20. 2)Application of coating material In this adsorption of coating material at the interface between core material and vehicle phase .it can be enhanced by increasing total interfacial energy of the system 3) Rigidisation of coating material The prepared microcapsules are stabilized by crosslinking (with formaldehyde), desolvation or thermal treatment.

21. Multiorifice centrifugation 1- Suspensions of core particles in liquid shell material are poured into rotating disc. 2- Due to the spinning action of the disc, the core particles become coated with the shell material. 3- The coated particles are then cast from the edge of the disc by centrifugal force. 4- After that the shell material is solidified by external means ( usuall cooling). - This technology is rapid, cost-effective, relatively simple and has high production efficiencies.

22. Pan coating: Solid particles are mixed with a dry coating material. The temperature is raised so that the coating material melts and encloses the core particles, and then is solidified by cooling. Or, the coating material can be gradually applied to core particles tumbling in a vessel rather than being wholly mixed with the core particles from the start of encapsulation.

23. Spray-Drying & spray-congealing : Microencapsulation by spray-drying is a low-cost commercial process which is mostly used for the encapsulation of frgrances,oils and flavors. Steps: 1- Core particles are dispersed in a polymer solution and sprayed into a hot 2- The shell material solidifies onto the core particles as the solvent evaporates. - The microcapsules obtained are of polynuclear or matrix type.

24. micro-encapsulation by spray-drying.

25. Spray drying

26. Spray-congealing : - This technique can be accomplished with spray drying equipment when the protective coating is applied as a melt. 1- the core material is dispersed in a coating material melt. 2- Coating solidification (and microencapsulation) is accomplished by spraying the hot mixture into a cool air stream. - e.g. microencapsulation of vitamins with digestible waxes for taste masking.

27. Solvent Evaporation It is the most extensively used method of microencapsulation. 1-Prepare an aqueous solution of the drug (may contain a viscosity building or stabilizing agent) 2- Then added to an organic phase consisting of the polymer solution in solvents like dichloromethane or chloroform with vigorous stirring to form the primary water in oil emulsion. 3- This emulsion is then added to a large volume of water containing an emulsifier like PVA or PVP to form the multiple emulsion(w/o/w). 4- The double emulsion is then subjected to stirring until most of the organic solvent evaporates, leaving solid microspheres. 5- The microspheres can then be washed and dried.

28. Polymerization This methods involve the reaction of monomeric unit located at the interface existing between a core material substance and a continuous phase in which the core material is dispensed .The continuous or core material supporting phase is usually a liquid or gas and there for the polymerization reaction occur at a liquid – liquid ,liquid-gas , solid-gas interface

29. Drug Preparation of polymerization mixture Initiation of polymerization Monodisoerse latex formation by polymer precipitation Recovery of polymeric micro particle Monomer (S)( eg;acrylamide , methacrylic acid ) +cross linker ( eg;methylene bis acrylamide ) Drug Alcohol Addition of alcoholic solution of the initiation( eg;AIBN 8hrs reaction time T(reaction)=60c.Nitrogen atmosphere

30. Application Sustained release or prolonged action medications Taste marked chewable tablets ,powders and suspension Single layer tablet containing chemically incompatible ingredients New formulation for creams, ointment, aerosols Pharmaceutically related areas such as hygiene ,diagnostic aid , and medical equipment design also amendable to microencapsulation application. Decrease the gastric irritation eg;KCl