Microencapsulation

Pharmaceutical technology

1. Presentation on the topic MICROENCAPSULATION Suman Kumar

2. Contents Introduction Fundamental Consideration Reason for Encapsulation Applications References

3. 1. Introduction MICROENCAPSULATION is a process by which very tiny droplets or particles of liquid or solid material are surrounded or coated with a continuous film of polymeric material. The product obtained by this process is called as Microcapsules .

4. Generally Micro particles consist of two components a) Core material. b) Coat or wall or shell material Fundamental Consideration

5. Core Material The material to be coated. It may be liquid or solid. Liquid core may be dissolved or dispersed material . Composition of core material: Drug or active constituent Additive like diluents Stabilizers

6. Coating Material Inert substance which coats on core with desired thickness . Composition of coating: Inert polymer Plasticizer Coloring agent Resins , waxes and lipids Release rate enhancers or retardants

7. Examples of Coating Materials 1. Water soluble resins- Gelatin, Gum Arabic, Starch , . …. Polyvinyl alcohol. 2. Water insoluble resins- Polyethylene, Polymethacrylate , … .. Polyamide (Nylon), Cellulose nitrate, Silicones. 3. Waxes and lipids- Paraffin, Carnauba, Beeswax, Stearic acid, . .. Stearyl alcohol, Glyceryl stearates . 4. Enteric resins- Shellac, Cellulose acetate phthalate, Zein.

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

9. Core Material Characteristic Property Purpose of Encapsulation Final Product Form Aspirin Slightly water- soluble solid Taste-masking; sustained release; reduced gastric irritation; separation of incompatibles Tablet or capsule Vitamin A Palmitate Nonvolatile liquid Stabilization to oxidation Dry powder Isosorbide dinitrate Water soluble solid sustained release Capsule Properties of Some Microencapsulated Core Materials

10. REASONS FOR ENCAPSULATION The core must be isolated from its surroundings , as 1. To protect reactive substances from the environment. 2. To convert liquid active components into a dry solid system. 3. To separate incompatible components for functional reasons. 4. To protect the immediate environment of the microcapsules from the active components.

11. To control the rate at which it leaves the microcapsule, as 1. To control release of the active components for delayed (timed) …. release or long-acting (sustained) release, 2. The problem may be as simple as masking the taste or odor of …. the core, 3. To Increase of bioavailability, 4. To produce a targeted drug delivery , 5. Protects the GIT from irritant effects of the drug, 6. Extension of duration of activity for an equal level of active …. agent .

12. PHARMACEUTICAL APPLICATION For masking the taste of bitter drugs Sugar or flim coating is generally used for masking unpleasent taste. For separation of incompatible ingredient. Incompatible drug can be formulated together by microencapsulation. Ex. Aspirin and chlorophentramine It reduces gastic irritation of some drug. Ex: ferrous sulphate , potassium chloride . 1

13. It reduces volatility of certain liquid. Ex: methyl salicylate , peppermint oil Useful to increase stability of drugs. Ex: Vitamin B1 and vitamin B2 Helpful to decrease hazards of toxic drugs Useful to decrease hydroscopic property of core material. Useful to improve flow properties before compression into tablet. 1

14. microorganism and enzyme immobilization . - Enzymes have been encapsulated in cheeses to accelerate ripening and flavor development. The encapsulated enzymes are protected from low pH and high ionic strength in the cheese. • The encapsulation of microorganisms has been used to improve stability of starter cultures.

15. Agricultural Applications Reduce insect populations by disrupting their mating process . P rotects the pheromone from oxidation and light during storage and release . Pesticides are encapsulated to be released over time, allowing farmers to apply the pesticides less amounts than requiring very highly concentrated and toxic initial applications followed by repeated applications to combat the loss of efficacy due to leaching, evaporation, and degradation.

16. Carbonless copy paper was the first marketable product to employ microcapsules. textile industry makes use of microencapsulated materials to enhance the properties of finished goods. One application increasingly utilized is the incorporation of microencapsulated phase change materials (PCMs). Application in day to day life

17. Food industry Most flavorings are volatile; therefore encapsulation of these components extends the shelf-life of these products. Some ingredients are encapsulated to mask taste, such as nutrients added to fortify a product without compromising the product’s intended taste Alternatively, flavors are sometimes encapsulated to last longer, as in chewing gum. Ingredients can also react with components present in the food system, which may limit bioavailability

18. There is a growing demand for nutritious foods for children which provides them with much needed vitamins and minerals during the growing age . Microencapsulation could deliver the much needed ingredients in children friendly and tasty way. Enhance visual aspect and marketing concept.

19. Techniques to Manufacture Microcapsules The technique of microencapsulation depends on the physical and chemical properties of the material to be encapsulated . The stability and the biological activity of the drug should not be affected, Yield and drug encapsulation efficiency should be high, Microsphere quality and drug release profile should be reproducible within specified limits, Microsphere should not exhibit aggregation or adherence. Process should be usable at an industrial scale.

20. Microencapsulation Techniques

21. Microencapsulation processes with their relative particle size ranges. Microencapsulation processes Applicable core materials Approximate particle size Air suspension Solids 35-5000 um Coacervation phase separation Solids and liquids 2-5000 um Multiorifice centrifugal Solids and liquids 1-5000 um Solvent evaporation Solids and liquids 5-5000 um Spray drying and congealing Solids and liquids 600 um

22. PHYSICAL OR PHYSICO-MECHANICAL METHODS Air-suspension or Wurster technique Inventions of Professor Dale E. Wurster Equipment ranging in capacities from one pound to 990 pounds. Micron or submicron particles can be effectively encapsulated by air suspension techniques.

23. AIR SUSPENSION APPARATUS

24. WORKING OF AIR SUSPENSION APPARATUS Microencapsulation by air suspension apparatus consist of dispersing of solid, particulate core material in a supporting air stream and the spray coating on the air suspended particles. Within the coating chamber particles are suspended on an upward moving air stream. When the particles flow through the coating zone portion of the chamber, the coating materials usually a polymer solution is spray applied to the moving particles.

25. During each pass through the coating zone, the core materials receive an increment of coating material. The cyclic process is repeated depending upon the thickness of the coating required. DISADVANTAGE : Agglomeration of the particles to some larger size is normally achieved.

26. Processing variables that receive consideration for efficient, effective encapsulation by air suspension techniques include the following: 1.Density, surface area, melting point, solubility, volatility, Crystallinity , and flow-ability of core the core material. 2.Coating material concentration (or melting point if not a solution). 3.Coating material application rate. 4.Volume of air required to support and fluidizes the core material. 5.Amount of coating material required. 6.Inlet and outlet operating temperatures

27. 2.Centrifugal extrusion Liquids are encapsulated using a rotating extrusion head containing concentric nozzles. This process is excellent for forming particles 400–2,000 μm 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 of microcapsules can be produced per nozzle per hour per head.

28. Centrifugal extrusion Process

29. WOKING A dual fluid stream of liquid core and shell materials is pumped through concentric tubes and forms droplets under the influence of vibration. The shell is then hardened by chemical cross linkings , cooling , or solvent evaporation. Different types of extrusion nozzles have been developed in order to optimize the process

30. 3. 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 and then coated with protective layers of various polymers.

31. Representation of a typical pan coating

32. 4. SPRAY DRYING AND SPRAY CONGEALING These methods have been used for many years as microencapsulation techniques.Because of certain similarities the two methods are discussed together. Microencapsulation by spray-drying is a low-cost commercial process which is mostly used for the encapsulation of fragrances, oils and flavors .

33. The equipment components of a standard spray dryer include an air heater, atomizer, main spray chamber, blower or fan, cyclone and product collector.

34. MICROENCAPSULATION BY SPRAY DRYING METHOD

35. Steps: SPRAY DRYING 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.

36. Spray congealing can be accomplished with spray drying equipment when the protective coating is applied as a melt. Core material is dispersed in a coating material melt rather than a coating solution. Coating solidification (and microencapsulation) is accomplished by spraying the hot mixture into a cool air stream. Airflow There are three modes of contact: Co-current Counter-current Mixed-flow

37. PHYSICO-CHEMICAL METHODS 1. Coacervation-Phase Separation Patents of B.K. Green et al. Three steps carried out under continuous agitation: Formation of three immiscible chemical phases Deposition of the coating Rigidization of the coating

38. Coacervation : - Two methods for coacervation are available, namely simple and complex processes. In simple coacervation , a desolvation agent is added for phase separation. Whereas complex coacervation involves complexation between two oppositely charged polymers.

39. Fig: Schematic representation of the coacervation process. First the core material (usually an oil) is dispersed into a polymer solution (e.g., a cationic aqueous polymer,gelatin ). The second polymer (anionic, water soluble, gum arabic ) solution is then added to the prepared dispersion. Deposition of the shell material onto the core particles occurs when the two polymers form a complex. This process is triggered by the addition of salt or by changing the pH, temperature or by dilution of the medium.

40. Finally, the prepared microcapsules are stabilized by crosslinking (with formaldehyde), desolvation or thermal treatment. Complex coacervation is used to produce microcapsules containing fragrant oils , liquid crystals , flavors , dyes or inks as the core material.

41. 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.

42. 2. Polymerization Interfacial polymer In Interfacial polymerization, the two reactants in a ….. polycondensation meet at an interface and react rapidly. 2) In-situ polymerization In a few microencapsulation processes, the direct ….. polymerization of a single monomer is carried out on the ….. particle surface.

43. e.g. Cellulose fibers are encapsulated in polyethylene while . immersed in dry toluene. Usual deposition rates are about ….. 0.5 μ m/min. Coating thickness ranges 0.2-75 μ m. 3) Matrix polymer In a number of processes, a core material is imbedded in a ….. polymeric matrix during formation of the particles. Prepares microcapsules containing protein solutions by incorporating the protein in the aqueous diamine phase.

44. REFERENCE 1.Theory and practice of industrial pharmacy by LEON LACHMAN HERBERT A. LIEBERMAN and JOSEPH L.KANIG Third edition,varghese publishing house, section III chapter 13-part three ,pages 412-429

45. 46 Jackson L. S.; Lee K. (1991-01-01). "Microencapsulation and the food industry". Lebensmittle– WissenschaftTechnologie . http://cat.inist.ft/?aModele=afficheN&cpsidt=5014466. Retrieved 1991-02-02 .