Microencapsulation

need, concepts of core and coat, method and evaluation of microencapsulation

1. Microencapsulation by Sampada Tamhankar

2. Contents 1.1 DEFINITION, NEED, CONCEPTS OF CORE AND COAT 1.2 METHODS OF MICROENCAPSULATION 1.3 EVALUATION OF MICROCAPSULES 2

3. 1.1 DEFINITION Microencapsulation is a means of applying relatively thin coatings to small particles of solids or droplets of liquids and dispersions Microencapsulation is a process by which solids, liquids and gases may be enclosed in microscopic particles by formation of thin coats around the core substance. Size of a microcapsule ranges from 50 nm to 2 mm CORE COATING by Sampada Tamhankar

4. 1.1 NEED/ REASONS FOR MICROENCAPSULATION To overcome the problems of conventional therapy To enhance the therapeutic efficacy of given drug To retard quick evaporation of volatile core material To prevent vitamins getting degraded due to oxidation For safe handling of toxic materials To ease handling of sticky and greasy material core To prevent radio-active material from chemical attack To achieve controlled or targeted release of drug To mask the odour and taste of unpalatable drugs by Sampada Tamhankar

5. 1.1 CONCEPTS OF CORE AND COAT Core can be defined as the material which is to be coated The core can either be solid, liquid or gaseous material The liquid core composition may be varied considering that the solute particles have been dissolved or dispersed The solid core can be single substance or mixture of active constituents along with stabilizers, diluents, excipients, etc. CORE by Sampada Tamhankar

6. 1.1 CONCEPTS OF CORE AND COAT Coat is the material which applied over the core material during encapsulation S election of coating material decides the physical and chemical properties of the resultant microcapsules While selecting a coating material following are the parameters that are to be taken under consideration including: Stability, volatility, release characteristics, environmental condition, etc. COAT by Sampada Tamhankar

7. 1.1 COATING MATERIAL Chemically modified carbohydrates P oly acryl dextran, P oly acryl starch Proteins Albumins, G elatin, Collagen Carbohydrates Starch, Carrageenan POLYMERS Polyanhydrides, Lactides, N ylon, Polyethylene, Teflon, E poxy polymers, Acrolein SYNTHETIC NATURAL by Sampada Tamhankar

8. 1.1 CONCEPTS OF CORE AND COAT The type of polymer used in microencapsulation is either hydrophilic/ hydrophobic or a combination of both Various coating materials that are widely used are : Gelatin PVA (polyvinyl alcohol) Ethyl cellulose CAP (cellulose acetate phthalate) The microcapsules may consist of a single particle or clusters of particles After isolation from the liquid manufacturing vehicle and drying, the material appears as a free flowing powder The powder is suitable for formulation as: compressed tablets hard gelatin capsules suspensions and other dosage forms by Sampada Tamhankar

9. MONONUCLEAR POLYNUCLEAR MATRIX Contain the shell around the core Many cores enclosed within the shell Distributed homogeneously in the shell material TYPES OF MICROCAPSULES RESERVOIR by Sampada Tamhankar

10. RELEASE MECHANISMS Microencapsulation aims at creating a coat wall around the core This wall is supposed to be ruptured during the time of use The rupturing occurs through various release mechanisms : By pressure or shear stress By melting the wall B y enzyme attack B y chemical reaction B y hydrolysis or slow disintegration By dissolving it under particular conditions, as in the case of an enteric drug coating by Sampada Tamhankar

11. 2.1 METHODS OF MICROENCAPSULATION Phase Separation Coacervation Wurster Process Spray Drying Interfacial Polymerization Multiorifice Centrifugal Process Pan Coating Solvent Evaporation Extrusion And Spheronisation by Sampada Tamhankar

12. 1) PHASE SEPARATION COACERVATION Process: It consists of three steps: Formation of three immiscible chemical phases – Liquid manufacturing phase, core material phase, coating material phase. Deposition of coating: Liquid polymer deposits on core material since it is immiscible polymer Rigidisation of coating: By thermal cross linking and desolvation techniques. Various coacervation phase separation methods are methods are: Temperature Change Method Incompatible Polymer Addition Method Non Solvent Addition Method Salt Addition Method Polymer- Polymer Interaction by Sampada Tamhankar

13. Phase Separation Coacervation DRUG Phase separation Formation of three immiscible phases COACERVATE DROPLET RIGIDISATION DUE TO COOLING POLYMERIC MEMBRANE SEPARATION SOLVENT EXTRACTION by Sampada Tamhankar

14. 1) PHASE SEPARATION COACERVATION A. Temperature change method Microencapsulation takes place by reducing temperature E.g. 2% Ethyl cellulose is dispersed in cyclohexane . The mixture is heated to boiling point to form a homogenous polymer solution. Core material e.g. paracetamol is dispersed in a solution ratio of coating material to core material is 1:2. Mixture is allowed to cool with continuous stirring This effects phase separation followed by coacervation. On further cooling gelation and solidification coating takes place. Microencapsulated product is collected from cyclohexane by filtration, decantation and centrifugation technique. by Sampada Tamhankar

15. 1) PHASE SEPARATION COACERVATION by Sampada Tamhankar

16. 2) WURSTER PROCESS (fluidized bed coaters) Only solid particles or porous particles can be encapsulated. Process : A bed or column of solid particles is suspended in a moving gas stream. A liquid coating solution is sprayed into the individual particles. Coating formulation is dried either by solvent evaporation or cooling. This coating and drying sequence is repeated until a desired coating thickness has been achieved. The coated particles then fall back down to the bottom of unit where a fresh coating is applied. Wurster Process by Sampada Tamhankar

17. 2) WURSTER PROCESS (fluidized bed coaters) Advantages : Applicable for wide range of materials E.g. Enteric coating Since multistage operation defects in coating can be minimised. by Sampada Tamhankar

18. 3) SPRAY DRYING AND RELATED PROCESSES Advantages: Since no cross linking it readily disperses in water. Low bulk density of microcapsules. Cost efficient process. Disadvantages: Organic solvents are flammable. Hence, they can not be used in spray drying. by Sampada Tamhankar

19. 3) SPRAY DRYING The core material is mainly liquid Process: Core is dispersed or emulsified with coating material Shell material is water soluble polymer such as gum Arabic or modified starch. The resulting solution is fed as droplets into heated chamber of a spray drier. Rapid evaporation of solvent takes place and droplets are dehydrated in heated chamber Dry capsules fall at bottom are of size is 10 to 300 µ. by Sampada Tamhankar

20. 3) SPRAY CONGEALING METHOD Molten coating material is thermally congealed Hot mixture is spread into cool air stream Using this method waxes, fatty acids, fatty alcohols, polymers and sugars that are solid at room temperature but meltable at reasonable temperature can be coated Spray congealing depends upon: Atomising wheel velocity, Speed rate, Viscosity by Sampada Tamhankar

21. 4) INTERFACIAL POLYMERIZATION The microcapsules will be formed at the surface of the droplet The substances used are multifunctional monomers These will be used either individually on in combination by Sampada Tamhankar

22. 4) INTERFACIAL POLYMERIZATION Process : The multifunctional monomer dissolved in liquid core material. i.e. they will be dispersed in aqueous phase containing dispersing agent The core material will be added in the organic phase and then mixed with aqueous phase Now rapid mixing of these two phases will occur reducing the interfacial tension This will lead to the polymerization of coating material from aqueous phase with the core material in organic phase forming the microcapsules which will be deposited at the bottom by Sampada Tamhankar

23. 5) MULTIORIFICE CENTRIFUGAL PROCESS This is a mechanical process for production of microcapsules which was developed by SWRI (South West Research institute). It utilises centrifugal force to cast a core material particle through enveloping microencapsulation membrane. Process : Three circumference groves are located within the cylinder. In intermediate grove orifice spaces closely and circumferentially around the cylinder. Carry the coating material in molten or solution form. Coating material under centrifugal force imparted by cylinder. Rotation flows outward. The embryonic microcapsules upon leaving the orifices are hardened congealed or voided of coating solution. by Sampada Tamhankar

24. 5) MULTIORIFICE CENTRIFUGAL PROCESS The processing variables are: Rotational speed of cylinder Flow rate of core and coating material. Viscosity and surface tension of coating material. Concentration of coating material by Sampada Tamhankar

25. 6) PAN COATING Suitable for solid particles greater than 600 microns in size are generally coated by pan coating E xtensively employed for the Preparation of controlled release beads by Sampada Tamhankar

26. 6) PAN COATING Process : In this method the coating material is applied as a solution or as an atomized spray to the desired solid core material in the coating pan T o remove the coating solvent, warm air is passed over the coated material to remove the excess as the coatings are being applied in the coating pans In some cases, final solvent removal is accomplished in drying oven Coating operation is repeated 3 to 4 times. Last coating of talc is applied. The pellets are rolled with dry air. The excess of talc is removed by vacuum. by Sampada Tamhankar

27. 7) SOLVENT EVAPOARTAION Solvent evaporation techniques are carried out in a liquid manufacturing vehicle (O/W emulsion) which is prepared by agitation of two immiscible liquids. For mixing the most common method is the use of a propeller style blade attached to a variable speed motor by Sampada Tamhankar

28. 7) SOLVENT EVAPOARTAION Process : Th e process involves dissolving microcapsule coating (polymer) in a volatile solvent which is immiscible with the liquid manufacturing vehicle phase. A core material (drug) to be microencapsulated 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 appropriate size microcapsules Agitation of system is continued until the solvent partitions into the aqueous phase and is removed by evaporation This process results in hardened microspheres which contain the active moiety by Sampada Tamhankar

29. 8) EXTRUSION AND SPHERONISATION CORE COAT by Sampada Tamhankar

30. 8) EXTRUSION AND SPHERONISATION CO EXTRUSION 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 linking, cooling, or solvent evaporation. Different types of extrusion nozzles have been developed in order to optimize the process by Sampada Tamhankar

31. 8) EXTRUSION AND SPHERONISATION by Sampada Tamhankar

32. 1.3 EVALUATION OF MICROCAPSULES PARTICLE SIZE LASER DIFFRACTOMETRY Approximately 30 mg microparticles is redispersed in 2–3 ml distilled water, containing 0.1% tween 20 for 3 min, using ultrasound. Then transferred into the small volume recirculating unit, operating at 60 ml/ s. Then the microparticle size is determined by laser diffractometer. by Sampada Tamhankar

33. 1.3 EVALUATION OF MICROCAPSULES SIEVE ANALYSIS Separation of the microspheres into various size fractions can be determined by using a mechanical sieve shaker. A series of five standard stainless steel sieves (20, 30, 45, 60 and 80 mesh) are arranged in the order of decreasing aperture size. Five grams of drug loaded microspheres are placed on the uppermost sieve. The sieves are shaken for a period of about 10 min, and then the particles on the screen are weighed. by Sampada Tamhankar

34. 1.3 EVALUATION OF MICROCAPSULES MORPHOLOGY OF MICROSPHERES Two methods can be used : S CANNING ELECTRON MICROSCOPE – The surface morphologies of microspheres are examined by a scanning electron microscope. MULTIMODE ATOMIC FORCE MICROSCOPE - A Multimode Atomic Force Microscope form Digital Instrument is used to study the surface morphology of the microspheres . by Sampada Tamhankar

35. 1.3 EVALUATION OF MICROCAPSULES VISCOSITY OF THE POLYMER SOLUTIONS The absolute viscosity, kinematic viscosity, and the intrinsic viscosity of the polymer solutions in different solvents can be measured by a U-tube viscometer. The polymer solutions are allowed to stand for 24 h prior to measurement to ensure complete polymer dissolution. by Sampada Tamhankar

36. 1.3 EVALUATION OF MICROCAPSULES DENSITY DETERMINATION The density of the microspheres can be measured by using a multi volume pycnometer. Accurately weighed sample in a cup is placed into the multi volume pycnometer. Helium is introduced at a constant pressure in the chamber and allowed to expand. This expansion results in a decrease in pressure within the chamber. Two consecutive readings of reduction in pressure at different initial pressure are noted. From two pressure readings the volume and density of the microsphere carrier is determined. by Sampada Tamhankar

37. 1.3 EVALUATION OF MICROCAPSULES DISSOLUTION Standard USP or BP dissolution apparatus have been used to study in vitro release profiles. Dissolution medium used for the study varied from 100-500 ml and speed of rotation from 50-100 rpm. by Sampada Tamhankar

38. Insert Image THANK YOU by Sampada Tamhankar