Microencapsulation in Novel Drug Delivery System

Microencapsulation is a process in which tiny particles or droplets are surrounded by a coating to give small capsules, with useful properties. In general, it is used to incorporate food ingredients, enzymes, cells or other materials on a micro metric scale.

1. Microencapsulation By- Prof. Vedanshu Malviya (M.Pharm-Pharmaceutics) Dr. Rajendra Gode Institute of Pharmacy, Amravati

2. Introduction Microencapsulation is a process by which solids, liquids, or even gases may be enclosed in microscopic particles by formation of thin coatings of wall material around the substance. Microencapsulation is defined as the application of a thin polymeric coating to individual core materials (tiny particles or droplets of liquids and dispersions ) that have an arbitrary particle size range from 5-5000 μm to give small capsules with many useful properties. Microencapsulation is a modified form of film coating , differing only in the size of the particles to be coated and the method by which this is produced

3. Advantages Patients to consume lower doses for the same therapeutic effect. Lowers the risk of side effects. Masking of odor or taste for chewable tablets , powders and suspensions for children's medicines. Prolong action dosage form and Controlled and targeted drug delivery. Modify the physical characters of a material which is required in certain formulations. Protect chemicals against degradative reactions such as oxidation, dehydration. Diagnostics and Medical equipment design. Liquids can be handled as solids. Safe and convenient handling of toxic substances

4. Disadvantages

5. Applications of Microencapsulation .

6. Type of Core materials, Coting materials and Vehicles used in Microencapsulation .

7. Fundamental Considerations a) Core material. The solid core can be mixture of active constituents, stabilizers, diluents , excipients and release-rate retardants or accelerators . b) Coat or wall or shell material Compatible, non reactive with core material Provide desired coating properties li k e s tren g th , flexibili t y , impermeability, optical properties, non hygroscopicity, tasteless and stable.

8. Cont… c) Core Material The material to be coated. It may be liquid or solid or gas. Liquid core may be dissolved or dispersed material. Composition of core material: Drug or active constituent Additive like diluents Stabilizers

9. Types of Coating Materials WATER SOLUBLE RESIN WATER INSOLUBLE RESIN WAX & LIPID ENTERIC RESIN Gelatin , Ethyl Cellulose, Paraffin, Shellac, Gum Arabic, Polyethylene, Carnauba Wax, Zein , PVP, CMC, Polymethacrylate , Cellulose Nitrate, Bees Wax, Stearic Acid, Cellulose Acetate Phthalate. Hydroxyl Methyl Cellulose, Silicones. Stearyl Alcohol. Arabino Galactan , Pol y vin y l Acrylate, Polyacrylic Acid.

10. Microspheres Microspheres are characteristically free flowing powders consisting of proteins or synthetic polymers which are biodegradable in nature and ideally having a particle size less than 200 μm. a. b.

11. Microparticles Micro particles are de f i n ed as par t icu l ate d isp e rs io n s or solid particles with a size in the range of 1-1000 μm. The drug is dissolved, entrapped, encapsulated or attached to a micro particle matrix. Schematic Representation of Micro particle

12. Difference between Microspheres and Micro particles As we know Microencapsulation is a technology used to entrap solids, liquids, or gases inside a polymeric matrix or shell. Two general micro morphologies of micro particles can be distinguished- microcapsules and microspheres.

13. Methods of Preparation .

14. I] Physical or Physico-mechanical methods Air Suspension Apparatus.

15. Cont… It consist of dispersing the solid particulate core material in supporting air stream and being coated with coating material (usually polymeric solution) In this, the fine core materials are suspended in a vertical current of air and sprayed with the coating material After evaporation of solvent, a layer of encapsulating material is deposited on core Gives improved control and flexibility as compared to pan coating. During each pass through the coating zone, the core material receives an increment of coating material. The cyclic process is repeated, perhaps several hundred times during processing, depending on the purpose of microencapsulation the coating thickness desired or whether the core material particles are thoroughly encapsulated. The supporting air stream also serves to dry the product while it is being encapsulated. Drying rates are directly related to the volume temperature of the supporting air stream.

16. Centrifugal Extrusion Liq u ids a re encapsu l ated using a rot a ting extrus i on he a d containing concentric nozzles. This process is excellent for forming particles 400–2,000 μm in diameter. Since t h e d rops are fo r m ed by the breakup of a l i q u id je t , the process is only suitable for liquid or slurry. A high pr o duc t ion rate can b e ac h ie v ed, i . e . , u p to 22. 5 k g of microcapsules can be produced per nozzle per hour per head. Heads containing 16 nozzles are available.

17. Pan Coating 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. Solid particles greater than 600 microns in size are generally considered essential for effective coating. Medicaments are usually coated onto various spherical substrates such as nonpareil sugar seeds, and then coated with protective layers of various polymers .

18. Figure of Pan Coating .

19. Spray Drying In m odern spray dryers the vi s c o si t y o f the solutions to be sprayed can be as high as 300mPa.s Spray drying and s pray conge a lin g - dispe r sing the c ore material in a liquefied coating substance and spraying . S p r ay dry i n g i s e f fect e d by rapid evapor a t i on of a solv e nt in which the coating material is dissolved. The equipment components of a standard spray dryer include an air heater, atomizer, main spray chamber, blower or fan, cyclone and product collector.

20. Figure of Spray Drying . Spray Drying: The coating solidification effected by rapid evaporating of solvent in which coating material is dissolved. Spray Congealing: The coating solidification is effected by thermally congealing a molten coating material. The removal of solvent is done by sorption , extraction or evaporation technique Steps: Core particles are dispersed in a polymer solution and sprayed into a hot chamber. The shell material solidifies onto the core particles as the solvent evaporates. - The microcapsules obtained are of polynuclear or matrix type.

21. Vibrational Nozzle The process works very well for generating droplets between 100–5,000 µm Units are deployed in industries and research mostly with capacities of 1–10,000 kg per hour at working temperatures of 20–1500 C. Nozzles heads are available from one up to several hundred thousand are available

22. Cont… .

23. II] Physico-chemical Methods Ionotropic gelation C h e m ical r ea ct ion b e t ween sodi u m alg i n a t e and c al c i u m chloride or other Counter ion solution such as barium chloride. Eg : Verapamil hydrochloride causes gastric irritation on sudden release. It is usually administered as conventional tablets containing 40-120 mg, 3 times a day. Due to its ready solubility in water and shorter half-life. Micro particulate system of verapamil hydrochloride for prolonged release delivery system.

24. a) Coacervation -Phase Separation Three steps carried out under continuous agitation: Formation of three immiscible chemical phases Deposition of the coating Rigidization of the coating Core material dispersion in solution of shell polymer; Separation of coacervate from solution; Coating of core material by microdroplets of coacervate ; Coalescence of coacervate to form continuous shell around core particles.

25. III] Chemical Process Solvent Evaporation In the case in which the core material is dispersed in the polymer solution, polymer shrinks around the core. In the case in which core material is dissolved in the coating polymer solution, a matrix - type microcapsule is formed. The core materials may be either water – soluble or water - insoluble materials. A variety of film - forming polymers can be used as coatings.

26. Cont… Step1: Formation of a solution/dispersion of the drug into an organic polymer phase. Step2: Emulsification of the polymer phase into an aqueous phase containing a suitable stabilizer, thus, forming a o/w emulsion. Step3: Removal of the organic solvent from the dispersed phase by extraction or evaporation leading to polymer precipitation and formation of the microspheres.

27. Polymerization A re l a tiv e ly new m ic r o e ncapsul a tion m ethod u t i l izes poly m e riz a tion techniques to from protective microcapsule coatings in situ. The method involve the reaction of monomeric unit located at the interface existing between a core material substance and continuous phase in which the core material is disperse. The core material supporting phase is usually a liquid or gas, and therefore polymerization reaction occur at liquid-liquid, liquid-gas, solid-liquid, or solid-gas interface. E.g. In the formation of polyamide (Nylon) polymeric reaction occurring at liquid-liquid interface existing between aliphatic diamine & dicarboxylic acid halide.

28. Cont… Interfacial polymer In In t e rfaci a l poly m e r i z a tio n , the two re a c tants i n a poly condensation meet at an interface and react rapidly. In-situ polymerization In a few microencapsulation processes, the direct poly m eriz a tion of a single m o no m er i s ca r ried o u t on the particle surface. e.g. Cellulose fibers are encapsulated in polyethylene while im m er sed i n dry toluen e . Usual deposi t ion rates are abo u t 0.5 μ m/min. Coating thickness ranges 0.2-75 μ m. 3 ) Matrix polymer In a n u m ber of p r oc e s s e s, a co r e m at e r i al i s i m bedded i n a polymeric matrix during formation of the particles. Prepa res m ic r ocapsu l es co n tai n ing p rot e in solu t io n s by incorporating the protein in the aqueous diamine phase. National Lead Corporation- utilizing polymerization techniques

29. Polymerization Technique

30. Evaluation Parameters Micromeretic Properties Angle of Repose Tap Density Bulk Density Carr’s Index Hauser's Ratio Percentage Yield Percent Drug Entrapment Percent Buoyancy Floating Time In-vitro Drug Release In-vivo Drug Release Ex-vivo Drug Release

31. Reference Leon, L., Herbert A. L., Joseph, L. K; “ The Theory And Practice Of Industrial Pharmacy”, 3rd edition (1990), Varghese Publishing House, Page no.- 412-428. S.S . Bansode , a review on “Microencapsulation”, International Journal of Pharmaceutical Sciences Review and Research, Volume 1, Issue 2, March – April 2010; Article 008; ISSN 0976 – 044X, Page no.- 38-43. N.K . SACHAN, a review on “Controlled Drug Delivery Through Microencapsulation ”, Malaysian Journal of Pharmaceutical Sciences, Volume 4, No. 1, Page no.- 65–81 (2006). H . Umer , a review on “Microencapsulation: Process, Techniques and Applications”, International Journal of Research in Pharmaceutical and Biomedical Sciences, Vol. 2 (2) Apr – Jun 2011, ISSN: 2229-3701, Page no.-447-481.