Methods of microencapsulation in Pharmtech.

Presented by Kabir Najeeb.
B.Pharm, MPH

1. VARIOUS METHODS OF MICROENCAPSULATION . PRESENTED BY: KABIR NAJEEB B.PHARM 2012 -16 ( Jamia Hamdard University) New Delhi, India.

2. Introduction: Microencapsulation is a process whereby a relatively thin coatings are applied on to the surface of solid particles or droplets of liquids and dispersions. This coatings are made into a thin layer of film over the particles to which they are intended to be applied. A good coating on a substance is that which can not be differentiated with an uncoated substance by visualizing with the naked eye. There are different types of coatings depending on its intended use on a material.

3. REASONS FOR COATING Taste masking: As in the case of drugs with a bitter or unpleasant taste. Target site: For example as in the case of enteric coated tablets which are meant to release their content in the intestine. Controlled or sustained release drugs: As in the case of drugs which intended use is to release drugs over a prolong period of time at a specific rate.

4. TECHNIQUES USED IN MICROENCAPSULATION There are 3 types of different techniques which are employed for this purpose. They are as follows : MECHANICAL METHOD CHEMICAL METHOD PHYSICOCHEMICAL METHOD.

5. MECHANICAL METHOD OF MICROENCAPSULATION PAN COATING: ASSEMBLY : PAN : The pan in which the particle to be coated are poured. It’s usually of different sizes ranging from 4, 6 or even 36 inches, depending on the quantity of material to be coated. It’s made from stainless steel .

6. SPRAY GUN : It’s a pump which delievers the coating solution into the pan. Pressure is required to send the coating solution onto the core material (material to be coated). Solution will flow out of the gun depending on its viscosity. Therefore if a solution is too viscous then it tends to resist from been properly spread out of the gun, thus solution should not be too viscous.

7. HOT AIR BLOWER PIPE : The core material becomes moist due to coating solution, thus the hot air blower pipe helps in drying it. The air should neither be too hot nor too cold. EXHAUST PIPE : To remove the excess heat that is been generated from the hot air blower as well as the rotating pan, an exhaust is used in the construction of a coating pan.

8. WORKING AND OPERATION OF THE COATING PAN The core material is filled into the coating pan upto 2/3 rd of the pan, the spray solution filled into the spray gun which is directed into the mouth of the pan at a height sufficient to provide even distribution of the spray solution onto the core. The hot air blower pipe also directed into the pan at a sufficient height to provide the core material with adequate air supply to dry the material. Also an exhaust pipe is connected to the mouth of the pan so as to evacuate excess heat which may degrade the coating or the core material. The pan is then made to rotate at an average speed of 18-40 rpm for a sufficient time to complete the coating.

9. PROCESSING VARIABLES : Speed of the pan should be in such a way that the core materials are evenly sprayed, it should neither be too high nor too slow. Air supply should not be too high to evaporate the coating substance and not be too hot to degrade the coating material as well as the core material.

10. The viscosity of the spray solution should not be too viscous to prevent its flow and get sprayed onto the core. The exhaust pipe should serve the purpose of removing excess heat out of the pan to avoid degradation of materials.

11. MERITS/ADVANTAGES OF COATING PAN METHOD: Operation is easy i.e does not require a technically sound person. Only one person can carry out the general operation.

12. DEMERITS/DISADVANTAGES: Relatively small amount of materials are coated at a time. Sometimes there is the need for further drying in the oven It’s a traditional means of coating

13. 2. WURSTER/ AIR SUSPENTION METHOD ASSEMBLY : CO NTROL PANEL : This comprises of the switches and buttons for the control and regulation of the moving parts on the coating chamber. COATING CHAMBER: This is the part of wurster apparatus that carries out the coating processes. The core materials are fed into this chamber. In the chamber there is an air distribution plate as well as nozzle for the application of film coating.

14. AIR DISTRIBUTION PLATE: This plate carries out the distribution of air in the chamber. The plate has many tiny holes which distributes air as it flows into the chamber, there by providing for even distribution of air. SPRAY NOZZLE : Just like a spray gun, the nozzle has the ability to release spray solution based on pressure.

15. WORKING AND OPERATION OF WURSTER APPARARUS Just as the name sounds air suspension apparatus, the working of this apparatus depends on air. The core materials (material to be coated), are fed into the coating chamber, in a quantity which is not more than 2/3 rd of the chamber (75% of the chambers capacity).

16. The control panel is used to set the speed of the air that flows into the chamber as well as the amount of coating materials (solution) coming out of the spray nozzle. After the material have been fed into the coating chamber and the air as well as the spray nozzle are set, and the operation began, the materials are seen suspended in the coating chamber due to the blowing action of the air, as the coating material oozing out of the spray nozzle gets them coated randomly. After sometimes the whole materials gets coated as well as dry due to the effect of the hot air from the air distribution plate. The machine is stopped and the coated materials are taken out.

17. PROCESSING VARIABLES : Density, surface area, melting point, and flowability of the core materials. Viscosity/concentration of the coating material (solution). Volume of air sufficient to suspend the core. Amount of coating materials.

18. MERITS/ADVANTAGES Cheap process in comparison to spray dryer method. Fast method of encapsulation. One person is required to carry out the process. Method for both micro as well as macro sized particles encapsulation.

19. DEMERITS/DISADVANTAGES Core materials of micron/submicron can be encapsulated effectively by this process but agglomeration into larger particles can occur. The size of the particle must be within the range that the air can suspend. More costly than pan coating.

20. The particle is embedded as in the figure below:

21. 3 . SPRAY DRYER METHOD ASSEMBLY: FEED TANK/MIXING TANK : The core materials and the coating solution are mixed together to form slurry. ATOMIZER : It’s at the top of drying chamber through which the slurry enters into the chamber. It breaks the slurry into droplets as it spins at the rate of 3000-50000 rpm (rounds per minute). Here centrifugal or spinning disc atomizer is been used .  

22. DRYING CHAMBER : This is the largest part of the spray dryer. It consists of the atomizer, the adjustable air dispenser. It carries out the whole process of spray drying. AIR HEATER : Supplies the hot air that enters into the drying chamber. ADJUSTABLE AIR DISPENSER : It spreads the air in the chamber as it comes in contact with the droplets from the atomizer.

23. CYCLONE PRODUCT COLLECTION : The microencapsulated product/powders are carried by the dry air into the cyclone and thus final products are collected. CHAMBER PRODUCT COLLECTION : Materials that are not carried into the cyclone by the air or those that sticks to the wall of the drying chamber are collected at the bottom of the drying chamber.

24. WORKING AND OPERATION OF SPRAY DRYER: The core material and the coating materials are mixed together into a solution or slurry in the mixing tank/feed tank, and introduced into the drying chamber. The slurry is then passed into the drying chamber via the spinning disc or centrifugal atomizer from the top. At the same time the dry air is heated by air heater to high temperature and introduced into the drying chamber via an air dispenser which is mounted around the atomizer.

25. As the slurry enters into the drying chamber, its broken down into droplets by the spinning disc atomizer or centrifugal atomizer at 3000-50000 rpm and dispersed into the heating chamber. Atomization at this point increases liquid surface area for minimum contact between air and liquid droplets. As the hot air flows in a rotational movement and thus gets evenly distributed in the whole chamber, when the hot air is in contact with the liquid mist, fast evaporation of the solvent begins, as the solvents evaporates from the droplets surface, solid particles are formed, which falls to the bottom of the chamber.

26. The hot drying gas flows through the spray drying chamber and carries the product to the cyclone. The hot drying air is eliminated through the air outlet into the atmosphere. Products which do not pass through the cyclone are collected in the collection chamber.

27. The set up is shown below:

28. PROCESSING VARIABLES: Quality of the core materials Viscosity of the coating materials. Balance between speed of atomizer and hot air.

29. MERITS/ADVANTAGES: The dry particles can be easily controlled. Thermo labile products can be spray dried at relatively high inlet temperatures. Short residence time is required. Minimum flavor loss as in sweetened particles. It ensures high product quality. Very fast means of microencapsulation .

30. DEMERITS/DISAVANTAGES: The equipment is very costly. Very bulky. Requires a technically sound person. Cleaning is time consuming. A lot of heat is wasted as thermal efficiency is low.

31. 4. SPRAY CONGEALING: This method is same as in the case of spray dryer, only that in this case the coating materials are not in the form of solution instead they are in molten form i.e they can melt at room temperature. And they are passed at a temperature of 30-40 degree. And cool air is passed into the chamber instead of hot air as in the case of spray dryer.  

32. 5.FLUIDIZED BED DRYER: This is a system of drying where by particles of solids are subjected to suspension by passing a gas onto the bed so the mixture of the duo behaves like a liquid, they are said to be fluidized. This method is efficient for drying of granules because each particle is surrounded by the drying gas. So in the case of microencapsulation, solid particles are subjected to fluidization with the coating materials in the form of gases, thus the intense mixing between particles and gaseous (coating) materials, results in uniform conditions of temperature, composition and particle size distribution throughout the bed.

33. CHEMICAL METHODS OF MICROENCAPSULATION POLYMERIZATION: This is a process where by relatively small molecules called monomers combine chemically to produce a very large chainlike or network of molecules called POLYMERS. The monomer molecules may be all alike or they may represent two, three or more different compounds. Usually at least 100 monomer molecules must be combined to make a product that has certain unique physical properties such as elasticity, high tensile strength, or the ability to form fibres that differentiate polymers from substances composed of smaller and simpler molecules; often, many thousands of monomer units are incorporated in a single molecule of a polymer.

34. PRINCIPLE OF POLYMERIZATION TECHNIQUE: In this technique, we use a type chemical reaction known as PHOTOPOLYMERIZATION REACTION. Photopolymerization reactions are chain-growth polymerizations which are initiated by the absorption of visible or ultraviolet light.  The light may be absorbed either directly by the reactant monomer ( direct   photopolymerization ), or else by a  photosensitizer  which absorbs the light and then transfers energy to the monomer. Microencapsulation by this process is archived when the drug has been enclosed in a polymer.

35. SOLUTION POLYMERIZATION: In a closed beaker take the core material along with the monomer. Allow the mixture to undergo photopolymerization by passing UV radiation for 8-10 hours, the UV radiation serves as the reaction initiator. A stirrer is introduced through a tiny opening at the top of the beaker. After a hazy solution develops which means the core material is enclosed by the coating material in the form of polymers formed by the reaction of monomers along with drugs by photopolymerization , thus microencapsulation is achieved.

36. EMULSION POLYMERIZATION: In this case 2 monomers from organic and inorganic forms are mixed together to form a polymer. Polymer is formed at the interphase of the organic and inorganic layers (oil and water layers) example of polymer is nylon. The core material i.e the drug as well as the organic phase and inorganic phase (oil and water monomers) are taken together in a beaker, UV radiation is used to initiate the polymer formation with stirring, the polymer is formed at the interphase with the drug embedded by the polymer.

37. PROCESSING VARIABLES: Amount of reaction to carry out the process. Ratio of drug to monomer. Reaction initiator i.e temperature or UV radiation.

38. PHYSICOCHEMICAL MICROENCAPSULATION This method of microencapsulation is carried out by coacervation -phase separation which consists of three steps as follows: 1. Formation of 3 immiscible chemical phases. 2. Deposition of coating over the core material. 3. Stabilizing the coating material on the core.

39. STEP 1 : FORMATION OF 3 IMMISCIBLE CHEMICAL PHASES : The 3 immiscible chemical phases are: Solvent (liquid manufacturing vehicle phase), a core material phase and a coating material phase. The 3 phases are formed thus: The core (drug) is dispersed in the polymer (coating material) which is containing the solvent (liquid manufacturing phase). The coating material phase (an immiscible polymer in a liquid state) is formed by any method of phase-separation coacervation which includes: temperature change, by salt addition, by polymer-polymer interaction.

40. STEP 2: DEPOSITION OF COATING OVER THE CORE MATERIALS: This is achieved by controlled or physical mixing of core and coating materials (while liquid). The deposition of polymer over the core material is easy when the interfacial energy of the system is low, there by enabling proper and easy embedding of the core in the coating material.

41. STEP 3: STABILIZING THE COATING MATERIAL ON THE CORE: The coating material is made to get rigid on the surface of the core by thermal, cross linking or desolvation technique .

42. METHODS OF PHASE SEPARATION COACERVATION 1. TEMPRATURE CHANGE: In this method, the solvent along with the polymer is taking and the temperature is raised to form a solution. The solution is allowed to cool and then gradually the core material is added slowly by continuous stirring with a stirrer. The temperature therefore becomes the dissolubilizing agent. Example: - Solvent: Cyclohexane Polymer: Ethyl cellulose Drug: Ascorbic acid Dessolubilizing agent: Temperature.

43. 2. INCOMPATIBLE POLYMER ADDITION: Example: - Polymer: Ethyl cellulose Core: Methyl blue Solvent: Toluene Dissolubilizing agent: Polymethylene . The polymer is dissolved in the solvent to form a solution. Polymethylene which is incompatible with the previous polymer is then added so as to dissolubilize the polymer i.e ethylcellulose . The core i.e drug is the added with stirring using a stirrer to form acervates . Thus the drug is embedded in the polymer.

44. 3. NON SOLVENT ADDITION: Example: - Solvent: Methyl ethyl ketone Polymer: Cellulose acetate butyrate (CAB) Core: Methylscopolamine Dissolubilizing agent: Isopropyl alcohol. The polymer is dissolved in the solvent to form a solution. Dissolubilizing agent is added drop wise to the solution. The drug is added by stirring continuously. Accervates are formed there by embedding the drugs. Hardening of the coated drug by oven drying.

45. 4. BY SALT ADDITION: This is based upon emulsion technique. Sodium sulfate is commonly used. Example: - Solvent: oil + water Polymer: Gelatin Core: Vitamin A ( Fat soluble vitamins A,D,E,K)

46. Gelatin in water solution (10%) to form a monophasic solution by heating at 37 degree and allow it to cool. To the solution, add oil with continuous stirring and thus water in oil emulsion is formed. The core (vitamin A) is added to the solution by stirring. The salt (Sod. sulfate) is added to the solution which causes the hardening of the solution at a certain concentration, thus the vitamin gets embedded.

47. 5. COMPLEX COACERVATION: In this method we form a coating on the drug using two polymers. Example: - Coating material: Acacia + gelatin Core: Methyl salicylate Solvent: Water Dissolubilizing agent: Ph/ isoelectric point.

48. Positive and negative charges from acacia and gelatin will form a complex which will form a layer on the drug. At a particular Ph they both have a neutral charge, but at ph 4.5 they have an opposite charge which will make them form a complex by hardening. Core (methyl salicylate ) is added by continues stirring. PROCEDURE: Gelatin + Acacia + water @ ph 4.5 Drug is added gradually with continuous stirring and thus drug gets embedded.