Microencapsulation

microencapsulation for M pharm pharmaceutics, 4th B pharm and 3rd pharm D students

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2. MICROENCAPSULATION SUHAIL K Lecturer Crescent College of Pharmaceutical Sciences [email protected] 2

3. 3 CONTENTS Introduction Fundamental considerations Methods of preparation Evaluation Applications

4. INTRODUCTION The word “ capsule ” implies a core and shell structure , and the term “ microcapsule ” state that, the membrane enclosed particle or droplets enclosed in solid matrix. Microencapsulation is a process by which very tiny droplets 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 micro particles, microcapsules. Particles having diameter between 3 - 800µm 4

5. ADVANTAGES To Increase bioavailability. To alter the drug release & separation of reactive core from other materials. To produce a targeted drug delivery. To reduce the reactivity of the core in relation to the outside environment. To decrease evaporation rate of the volatile core material. To convert liquid to solid form & To mask the core taste. Protects the GIT from irritant effects of the drug. Prevents the oxidative degradation of drugs . 5

6. DISADVANTAGE It’s a costly process . Incomplete or discontinues coating Required skill . It is difficult to get continuous & uniform film. Possible cross reaction between the core and coating material. Unstable release characteristics of coated products. 6

7. FUNDAMENTAL CONSIDRATION Basic understanding of the general properties of microcapsules, such as the nature of the coating materials, the stability and release characteristics of coated materials, and the microencapsulation method employed. 7

8. Core material Coating material Vehicle Solid Liquid Microencapsulation Polymers Proteins Resins Waxes polysaccharide Aqueous Non aqueous 8

9. CORE MATERIAL The core material is defined as the specific material to be coated. It may be liquid or solid. solid core may be dissolved or dispersed material. Core material composition provides effectual design and development of the microencapsule properties. COMPOSITION OF CORE MATERIAL: Drug or active constituent Additive like diluents Stabilizers 9

10. PROPERTIES OF SOME MICROENCAPSULATED CORE MATERIALS. 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 Acetaminophen Slightly water- soluble solid Taste-masking Tablet 10

11. COATING MATERIAL Inert material which coats on core with desired thickness. IDEAL CHARACTERISTICS capable of forming a film cohesive with core material. Chemically compatible with the core material . Should be stable, non reactive and cheap. Provide desired coating properties like strength, flexibility and impermeability. 11

12. COMPOSITION OF COATING Water soluble resins Eg : gum arabic , polyvinylpyrrolidone , methyl cellulose, HEC Water insoluble resins Eg : ethyl cellulose, polyethylene Waxes and lipids Eg : paraffin, beeswax Enteric resins Eg : shellac, zein , CAP Protiens Colorants Plasticizers 12

13. MECHANISM OF DRUG RELEASE Include; Diffusion Dissolution Osmosis Erosion 13

14. METHODS OF PREPARATION Preparation of microspheres should satisfy certain criteria: The ability to incorporate reasonably high concentrations of the drug. Stability of the preparation after synthesis with a clinically acceptable shelf life. Controlled particle size and dispersability in aqueous vehicles for injection. Release of active reagent with a good control over a wide time scale. Biocompatibility with a controllable biodegradability. 14

15. MICROENCAPSULATION METHODS A ir suspension C oacervation- phase separation M ultiorifice-centrifugal process S pray drying and spray congealing P an coating S olvent evaporation techniques P olymerization C o extrusion 15

16. AIR SUSPENSION: Particulate core materials are dispersed in a supporting air stream. The coating material is sprayed on the air suspended particles. Particle size range 35 – 5000 μ m. During each pass through the coating zone, the core material receives an increment of coating material. 16

17. The cyclic process is repeated, perhaps several hundred times during processing, depending on: the purpose of microencapsulation the coating thickness desired Commonly used – gelatin , ethyl cellulose, polyethylene , stearic acid. The supporting air stream also serves to dry the product while it is being encapsulated. 17

18. WURSTER AIR SUSPENSION APPARATUS Patented by Wurster in 1950.Salient features of wurster process are:- 1.Coating chamber 2. Air distribution plate drilled with large diameter holes in the central portion than those in the periphery. 3. Spray nozzle located at the center of the air-distribution plate. 18

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20. Different types of fluid bed coaters include top spray, bottom spray and tangential spray . 20

21. 2. COACERVATION-PHASE SEPERATION Process consist of 3 steps Formation of three immiscible chemical phase Deposition of the coating Rigidization of coating 21

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23. Formation of three immiscible chemical phase A liquid manufacturing vehicle phase A core material phase A coating material phase To form the 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. 23

24. The coating material phase, an immiscible polymer in a liquid state, is formed by utilizing one of the following phase separation coacervation method Temperature change method Nonsolvent addition Salt addition Incompatible polymer addition Polymer-polymer interaction 24

25. 2 . Deposition of coating material This is accomplished by controlled, physical mixing of the coating material and core material in the manufacturing vehicle. Deposition of the liquid polymer coating around the core material occur if the polymer is adsorbed at the interface formed between the core material and the liquid vehicle phase. 25

26. 3. Rigidization of coating By thermal, cross linking or desolvation technique to form a self sustaining microsphere. 26

27. Temperature change method Change in temperature cause separation of coating material from the solvent. At a particular temperature the polymer concentration the binary system (polymer+ solvent) become homogeneous. Add the core materials. The temperature decreases from that point. Phase separation of the dissolved polymer occurs in the form of immiscible liquid droplets. 27

28. If core material is present in the system, under proper polymer concentration, temperature, and agitation conditions, the liquid polymer droplets coalescence around the dispersed core material particles and forming the embryonic microcapsules. Coacervtion induced thermally-phase diagram 28

29. Example, Ethyl cellulose, a water insoluble polymer, is applied to a water soluble core material, N-acetyl p-amino phenol. Polymer solvent is cyclohexane EC is insoluble at room temperature. Soluble in elevated temperature. 29

30. Incompatible polymer addition It is accomplished by utilizing the incompatibility of dissimilar polymer existing in a common solvent. e.g. addition of polybutadiene to the solution of ethylcellulose in toluene ( methylene blue as core material). 30

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32. 32 Addition of salt. Addition of soluble inorganic salts to aqueous solution of certain water soluble polymers to cause phase separation. e.g. addition of sodium sulphate solution to gelatine solution in vitamin encapsulation.

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34. 34 Addition of nonsolvent A liquid that is a non solvent for a given polymer can be added to a solution of polymer to induce phase separation e.g. addition of isopropyl ether to methyl ethyl ketone solution of cellulose acetate butyrate ( methylscopolamine hydrobromide is core).

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36. 36 Inducing polymer – polymer interaction. The interaction of oppositely charged polyelectrolytes can result in the formation of a complex having such reduced solubility that cause phase separation. Eg . Gelatin and gum arabic for methyl salicylate core.

37. 2. MULTIORIFICE-CENTRIFUGAL PROCESS It is a mechanical process for producing microcapsules. Main coating materials- gelatin , polyvinylpyrrolidone , polyvinyl alcohol , ethyl cellulose , paraffin … centrifugal forces are used to hurl a core material particle through an enveloping microencapsulation membrane. The multiorifice -centrifugal process is capable for micro encapsulating liquids and solids of varied size ranges, with diverse coating materials. The encapsulated product can be supplied as - slurry in the hardening media - dry powder. 37

38. Apparatus and working Equipment used consist of A rotting cylinder (1) 3 grooves within the above cylinder (2,3,4). grooves 2+4 carry the coating material in moltan or solution form via tubes(5). A counter rotating disc(7) is mounted within the cylinder, disperse the core material fed through the centrally located inlet(8). The coating material(6) under centrifugal force imparted by the cylinder rotation, flows outward along the sides of the immediate groove into the counter sink portion and forms a film across the orifice. 38

39. A counter rotating disc(7), mounted within the cylinder, atomizes or disperse the core material. The rotating disc flings the particulate core material towards the orifice. Core material in the orifice, encounters the coating material membrane. By the impact of centrifugal force, hurls the core material through the enveloping coating membrane. Upon leaving the orifice the microcapsules are hardened, congealed by different mean. 39

40. Processing variables include ; Rotating speed of the cylinder Flow rate of core, coating material Concentration and viscosity of coating material Viscosity and surface tension of core material 40

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42. 3. PAN COATING Solid particles greater than 600micron in size Medicaments are coated on to various spherical substrates such as nonpareil sugar seeds and then coated with protective layer of various polymer. Coating is applied as a solution or atomized spray to the solid core material in the coating pan. Coating solvent is removed by passing warm air over the coated material. 42

43. In some cases, final solvent removal is accomplished by drying in an oven. Example ; preparation of sustained released pellets of dextroamphitamine sulphate , which is first coated onto nonpareil seed and then coated with release rate retarding wax-fat coating. 43

44. 44 ELECTROSTATIC DEPOSITION The method is suitable for both solids and liquid droplets core and coating material are imparted electric charges by means of high voltage. Core is charged and placed in coating chamber. coating material is charged in solution when it leave the atomizer devices prior to spray mist. Both are oppositely charged and coating material gets deposited on core material.

45. 4 . SPRAY DRYING AND SPRAY CONGEALING These two process are similar, both involves dispersing the core material in a liquefied or solution of coating substance and spraying or introducing the core-coating mixture into same environmental condition where by relatively rapid solidification of coating is effected. Spray drying : Core particles are dispersed in a polymer solution and sprayed into hot air. The shell material solidifies onto the core material as the solvent evaporates. The microcapsules obtained are of polynuclear . 45

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47. Spray congealing: The core material is dispersed in a coating material melt. Coating solidification and microencapsulation is accomplished by spraying the hot mixture into a cool air stream. Eg : microencapsulation of vitamins with digestible waxes for taste masking. By this two we get microsphere in the size range of 5-600micron, low bulk density. 47

48. 5. SOLVENT EVAPORATION. Coating material is dissolved in a volatile solvent, which is immiscible with the liquid manufacturing vehicle phase. Core material to be encapsulated is dissolved or dispersed in the coating polymer solution. With agitation, the core coating material mixture is dispersed in the liquid manufacturing vehicle phase to obtain microcapsule. The mixture is then heated to evaporate the solvent from the polymer. Used to produce microcapsule of liquid and solid core. 48

49. 49 6. RAPID EXPANSION OF SUPERCRITICAL FLUIDS Supercritical fluids are highly compressed gasses. A small change in temperature or pressure cause a large change in the density of supercritical fluids near the critical point. Widely used are supercritical carbon dioxide, alkanes and nitrous oxide.

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51. 51 Supercritical fluid containing the active ingredients and the shell material are maintained at high pressure and then released at atmospheric pressure causes dessolvation of the shell material, which is then deposited around the active ingredient and forms a coating layer. DISADVANTAGES Ingredients must be soluble in supercritical fluids.

52. 7. POLYMERIZATION A relatively new microencapsulation method; utilizes polymerization techniques to form protective microcapsule. The method involves the reaction of monomeric units located at the interface existing between a core material substance and a continuous phase in which the core material is dispersed. 52

53. 53 Interfcial polymerization (IFP) The capsule shell will be formed at the surface of the droplets or particles by polymerization of the reactive monomers by adding co reactant. Generally used monomer include multifunctional isocyanates and multifunctional acid chlorides. Monomers dissolved in liquid core material. A co reactant multifunctional amine will be added the mixture. This results in rapid polymerization at interface. A poly urea shell will be formed when isocyanate react with amine.

54. 54 Insitu polymerization Like IFP the shell formation occur because of polymerization of monomers. In this process, no reactive agents are added to the core material. Polymerization occurs exclusively in the continuous phase. Initially a low mol. wt prepolymer will be formed and then to polymer shell.

55. 55 8. CO EXTRUSION A dual fluid stream of liquid shell material and core is pumped through concentric tube and forms droplets under the influence of vibration. shell is then hardened by cooling or solvent evaporation. Different types of extrusion nozzles have been developed inorder to optimize the process.

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57. 57 9.SPINNING DISC suspension of core particles in liquid shell material are poured into a rotating disc. Due to the spinning action of the disc the core particles become coated with shell material. the coated particles are then cast from the edge of the disc by centrifugal force. After that the shell material is solidified by external means. Method is rapid, easy, cost effective and effectiveness.

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59. 59 Microencapsulation process Applicable core material Approximate particle size (µm) Air suspension solids 35-5000 Coacervation -phase separation Solids and liquids 2-5000 Multiorifice centrifugal solids 1-5000 Pan coating solids 600-5000 Solvent evaporation Solids and liquids 5-5000 Spray drying and congealing Solids and liquids 600-5000 Microencapsulation process and their applicabilities .

60. EVALUATION OF MICROCAPSULES Percentage Yield The total amount of microcapsules obtained was weighed and the percentage yield calculated taking into consideration the weight of the drug and polymer . 60

61. 61 SIEVE ANALYSIS Separation of the microsphere into various size fraction can be determined by using a mechanical sieve shaker MORPHOLOGY OF MICROSPHERE The surface morphologies of microspheres are examined by SEM and ESCA. PARTICLE SIZE Conventional light microscopy and SEM BULK DENSITY

62. 62 SOLUBILITY OF POLYMER Solution turbidity is a strong indication of the solvent power. Cloud point can be used for the determination of the solubility of powder. INVITRO METHODS DISSOLUTION STUDY Standard USP dissolution apparatus have been used for the study. Medium used for the study varied from 100-500ml and speed of rotation from 50-100rpm

63. 63 CAPTURE/ENTRAPMENT EFFICIENCY It can be determined by allowing washed microsphere to lyses. The lysate is then subjected to the determination of active constituents as per monograph.

64. APPLICATIONS OF MICROENCAPSULATION IN DRUG THERAPY. The technology has been used widely in the design of controlled release and sustained release dosage forms. To mask the bitter taste of drugs like Paracetamol , Nitrofurantoin etc. To reduce gastric and other G.I. tract irritations. Liquid can be converted to pseudo-solid for easy storage and handling. Eg ; eprazinone . Protection of core material against external effect. Targeted drug delivery system. prolong the action 64

65. 65 REFERENCE Lachman L, Lieberman HA, Kaning JL. The theory and practice of industrial pharmacy. 3 rd ed. Varghese publishers; p. 412-28. Vyas SP, Khar RK. Targeted and controlled drug delivery novel carrier system. New delhi . p.410-35. Bansode SS, Banarjee SK, Gaikwad DD, Jadhav SL, Thorat RM. Microencapsulation: a review, vishal institute of pharmaceutical education and research ale, Pune,1(2) Gupta AK, Dey CK. Microencapsulation for controlled drug Delivery: a comprehensive review. Sunsari Technical College Journal, 1(1), October 2012.

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