Microencapsulation, Unit-II, BP704T: NDDS, Sem-VII, Final Year B. Pharm (SPPU 2019P).pptx

Unit-II.
Microencapsulation: Definition, advantages and disadvantages, microspheres
/microcapsules, microparticles, methods of microencapsulation, applications.

1. Unit-II: Microencapsulation: Definition, advantages & disadvantages, microspheres / microcapsules, microparticles, methods of microencapsulation, applications. Mucosal Drug Delivery system: Introduction, Principles of bioadhesion / mucoadhesion, concepts, advantages & disadvantages, transmucosal permeability & formulation considerations of buccal delivery systems. Implantable Drug Delivery Systems: Introduction, advantages & disadvantages, concept of implants & osmotic pump.

2. MICROENCAPSULATION Ms. Kartiki M. Bhandari Assistant Professor (Pharmaceutics)

3. DEFINITION Process in which solids, liquids, or gases are enclosed within microscopic particles (such as polymers) by formation of a thin coat of coating material.

4. OBJECTIVE / NEED OF MICROENCAPSULATION? Unpleasant t aste Unpleasant o dour Drug d egradation in stomach GI i rritation Sustained, prolonged, delayed, or c ontrolled r elease Drug-drug in compatibility Mnemonic : “CR in odit”

5. MICROENCAPSULATION Size: 0.1 to 100 μ m Core: API in solid / liquid / gas state. Ex: Aspirin, vitamins, NaCl, castor oil, etc. Coat: Inert polymer coat enclosing core API. Ex : Gum (gum arabica, sodium alginate) ; carbohydrate (starch, dextran, sucrose) ; cellulose (methyl cellulose, HPMC) ; lipid (beeswax, stearic acid, phospholipid) ; protein (gelatin, albumin) ; etc. Core / API Polymer Coat

6. PROPERTIES OF COATING MATERIAL Stabilization of core material. Inert toward API. Controlled release under specific conditions. Film-forming, pliable, tasteless, stable. Non-hygroscopic, no n- viscous, economical. Solubilize or melt in an aqueous media or solvent. F lexible, brittle (to release drug at desired site), hard (to prevent drug loss before formulation reaches its active site), thin coat. Core / API Polymer Coat

7. EXAMPLES OF COATING MATERIAL Water-insoluble resins: EC Polyethylene Polymethacrylate Polyamide (Nylon) Poly (Ethyl vinyl acetate) Cellulose nitrate Silicones PLGA Waxes & lipids: Paraffin Carnauba Spermaceti Beeswax Stearic acid Stearyl alcohol Glyceryl stearate Enteric resins: Shellac Cellulose acetate phthalate zein Water-soluble resins: Gelatin Gum Arabic Arabinogalactan Starch PVA PVP Polyacrylic acid Methyl cellulose CMC Hydroxy ethyl cellulose

8. ADVANTAGES / APPLICATIONS Taste masking (ampicillin, aminophylline). Odour masking (castor oil, cod liver oil). Environmental protection (vitamins, palmitate). Improve flow properties (thiamine). Reduce hygroscopicity (NaCl, KCl). Reduce vaporization of volatile drugs (methyl salicylate). Convert liquids to solids (clofibrate, castor oil).

9. ADVANTAGES / APPLICATIONS Avoid drug-drug incompatibilities (aspirin + chlorpheniramine maleate). Reduce GI irritation (paracetamol, KCl, ferrous sulphate, penicillin). Improve stability (than nanoemulsion / liposome) & provide controlled drug release. Improve drug handling & storage (fluffy drugs / drugs with less flowability). Handling of toxic materials (insecticides, pesticides). Applications in agriculture, food, & essential oil industries.

10. DISADVANTAGES Expensive. More skills / knowledge required. Not suitable for all drugs. Chances of cross contamination of drug & polymer. May lead to incomplete or discontinuous coat. Polymers can be toxic. Half life of hygroscopic drugs may reduce.

11. MICROPARTICLES Spherical shaped micrometric matrix system. Particle size range: 1-1000 μ m. Drug is dissolved/ entrapped/ encapsulated/ attached (reservoir/ matrix). Uniform physical dispersion of drug in polymer matrix.

12. MICROSPHERES Small, spherical, free-flowing particles. Particle size range: 1-1000 μ m. Drug distributed in polymer matrix . Often termed as Microparticles . Distributed drug Polymer matrix

13. MICROCAPSULES Drug enclosed in uniform wall around it. Core is enclosed within microcapsule. Drug coated by polymer reservoir . Drug core Polymer reservoir

14. CLASSIFICATION OF MICROCAPSULES

15. DRUG RELEASE MECHANISM Mechanical rupture of the capsule wall Dissolution of the wall Melting of the wall Diffusion through the wall

16. DRUG RELEASE MECHANISM Degradation controlled monolithic system: Dr ug is dissolved & distributed uniformly in matrix. It is strongly attached to matrix & released on degradation of matrix . Drug diffusion is slow as compared to matrix degradation. Diffusion controlled monolithic system: API is released by diffusion prior to or concurrent with polymer matrix degradation . Release rate depend upon where the polymer degrades by homogeneous or heterogeneous mechanism.

17. DRUG RELEASE MECHANISM Diffusion controlled reservoir system: API is encapsulated by rate controlling membrane through which drug diffuses & membrane erodes only after its delivery is completed. Drug release is unaffected by matrix degradation. Erosion: Polymer coat e rode due to pH / enzymatic hydrolysis causing drug release with certain polymers like glyceryl monostearate, beeswax, stearyl alcohol, etc.

18. EVALUATION TESTS Particle Size & Shape: Light microscopy & electron microscopy both are used to determine particle size & shape. Density Determination: The density of the microcapsule can be measured by using a multi volume pycnometer. Isoelectric Point: The micro electrophoresis is an apparatus used to measure the electro phonetic mobility. Contact Angle: The angle of contact is measured to determine the wetting property of microcapsule. In-vitro release Studies: Release studies for microcapsules can be carried out in different pH condition like pH 1.2 & 7.4 using USP rotating basket.

19. AIR SUSPENSION TECHNIQUE Also k/a Wurster or Fluidized bed coating. Invented by Dale E. Wurster (1940). Dispersion of solid core material in air stream , & spray congealing of these air suspended particles.

20. AIR SUSPENSION TECHNIQUE

21. MERITS DEMERITS Rapid Easy to use Labour not required Superior coating quality Require less coating material Suitable only for solid material Not suitable for heat-sensitive material Size / shape of microcapsules depend on various process variables. Equipment cost is high

22. MULTI-ORIFICE CENTRIFUGAL PROCESS For solids (after dispersion in some liquids) as well as liquids . Particles formed have diameter between 400-2000 μ m. High production rate ( 50-75 pounds / hr ). Embryonic-shaped microcapsules.

23. MULTI-ORIFICE CENTRIFUGAL PROCESS

24. PAN COATING METHOD Widely used oldest industrial method for forming small coated particles or tablets of solid drug core. Particles formed have diameter between 600-5000 μ m. Used extensively for forming controlled-release beads.

25. PAN COATING METHOD

26. SPRAY DRYING / CONGEALING PROCESS Feed in fluid state is sprayed into hot drying medium & get transformed into a dried particulate state. Drug is dispersed in a conc. solution of coating material to obtain emulsion which is atomised in specific atmospheric condition for rapid drying. Difference in both processes is in methods used for solidification of coat.

27. SPRAY DRYING v/s SPRAY CONGEALING

28. SPRAY DRYING v/s SPRAY CONGEALING SPRAY DRYING Common, economic; suitable for heat-labile drugs due to short contact time. Viscosity of spray solution can be as high as 300 centipoise. SPRAY CONGEALING Form spherical particles with the diameter 5-600 μ m. Core is dispersed in melt of wax, fatty acid, alcohol, polymer, sugar, etc. Hence, used for taste-masking or other purposes ( NOT for CRDDS ).

29. SPRAY DRYING PROCESS

30. SPRAY CONGEALING PROCESS

31. PHASE SEPARATION-COACERVATION Term “ coacervate ” is derived from Latin word “ acervus ” meaning heap / aggregation. Tiny spherical droplets in which various organic molecules (lipid molecules) are held together by hydrophobic forces from a surrounding liquid are termed as “Coacervates.” This separation of 2 phases i.e. small droplets of dense polymer-rich phase & dilute liquid phase is termed as “Coacervation.”

32. PHASE SEPARATION-COACERVATION Suitable for both solid & liquid core ( oils in O/W form without stabilizers). Subdivided into: Simple Coacervation: Uses one colloid, which precipitates out by salts / non-solvents / by variation in temperature. Complex Coacervation: Involves two or more colloids, salted out by oppositely-charged polymers (acacia & gelatin).

33. PHASE SEPARATION-COACERVATION It involves 3 stages: Formation of 3 immiscible chemical phases (vehicle, core & coating material) & dispersion of core material in the coating polymer solution. Deposition of coating material around the core material by the microdroplets followed by separation of coacervates from the solution. Formation of polymeric membrane around the core particles by rigidization (hardening) of the coat.

34. PHASE SEPARATION-COACERVATION

35. IONOTROPIC GELATION B ased on the ability of polymers to cross-link, in the presence of counter ion, leading to the formation of hydrogels. Examples of polymers used: Sodium alginate, gellan gum, chitosan, etc. Polymer: Sodium alginate Counter ion: Calcium (CaCl 2 ) Hydrogel: Encapsulated calcium in alginate + NaCl ↓

36. IONOTROPIC GELATION

37. POLYMERIZATION P olymerization takes place by a chemical reaction which occurs between the monomers A & B . Initiated by changes in PH (by introduction of acid/base) &/or temperature. Can be accelerated by the use of catalysts. Polymer formed is deposited around the drops of core material which leads to encapsulation.

38. POLYMERIZATION

39. SOLVENT EVAPORATION Used for microencapsulating hydrophobic / hydrophilic / solid / liquid core . C arried out by using emulsion-based systems including O/W emulsion & W/O/W double emulsions. If core is dispersed in polymer, polymer shrinks around the core ( reservoir ). If core is dissolved in polymer, matrix-type microcapsules are formed.

40. SOLVENT EVAPORATION

41. FACTORS AFFECTING ENCAPSULATION EFFICIENCY High solubility of the polymer in organic solvent (solvent cannot evaporate faster). Low concentration of polymer (polymer will evaporate with solvent). Low solvent removal rate ↓ Slow solidification of microparticles ↓ Low encapsulation efficiency

42. FACTORS AFFECTING ENCAPSULATION EFFICIENCY Low solubility of polymer in organic solvent (faster solvent evaporation). High concentration of polymer (polymer will not evaporate with solvent). High solvent removal rate ↓ Fast solidification of microparticles ↓ High encapsulation efficiency

43. PROCESS OF MICROENCAPSULATION

44. ANY QUESTIONS??