Microencapsulation

This presentation contains all about microencapsulation

1. A P resentation on Microencapsulatio n Presented by Md. Shimul Bhuia St.ID: 16PHR003 Department of Pharmacy Bangabandhu Sheikh Mujibur Rahman Science and Technology University Gopalganj-8100 Course Title: Pharmaceutical Technology-II Course Code: PHR361

2. Defination 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. Microencapsulation may be defined as the process of surrounding or enveloping one substance within another substance on a very small scale, yielding capsules ranging from less than one micron to several hundred microns in size.” It is mean of applying thin coating to small particle of solid or droplet of liquid & dispersion. Microencapsulation is a process by which solids, Liquids or even gases may be enclosed in microscopic particles by formation of thin coatings of wall material around the substances INTRODUCTION

3. Particle size: 50-5000 micron. 2 phases: a) Core material b) Coating material The prod u ct ob t ai n ed b y t h is pr o c e ss is ca lled as m i c ro p art ic les, microcapsules, microsphere, coated granules, pellets.. Particles having diameter between 3 - 800µm are known as micro particles or microcapsules or microspheres. Particles larger than 1000µm are known as Macroparticles .

4. A well designed controlled drug delivery system - can overcome some of the problems of conventional therapy. - enhance the therapeutic efficacy of a given drug.

5. To obtain maximum therapeutic efficacy, drug is to be delivered : -to the target tissue -in the optimal amount -in the right period of time there by causing little toxicity and minimal side effects . One such approach is using microspheres as carriers for drugs. Microspheres are characteristically free flowing powders consisting of proteins or synthetic polymers biodegradable in nature particle size less than 200 μm.

6. Generally Micro particles consist of two components a) Core material. The solid core can be mixture of active constituents, stabilizers, diluents, excipients and release-rate retardants or accelerators. b) Coat or wall or shell material Compatible, non reactive with core material Provide desired coating properties li k e s tren g th, flexibili t y , impermeability, optical properties, non hygroscopicity, tasteless and stable Fundamental Consideration / Formulation considerations

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

8. 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 ROLE OF POLYMERS : Polymers are substances of high molecular weight made up by repeating monomer units. Polymer molecules may be linear or branched, and separate linear or branched chains may be joined by crosslinks. Polymers are used widely in pharmaceutical systems as adjuvants, coating materials and, a components of controlled and site- specific drug delivery systems

9. List of coating material Water soluble resin Water insoluble resin Wax & lipid Enteric resin Gelatin, Ethyl cellulose, Paraffin, Shellac, Gum arabic, Polyethylene, Carnauba wax, Zein, PVP, CMC, Polymethacrylate, Cellulose nitrate, Bees wax, Stearic acid, Cellulose acetate phthalate. Methyl cellulose, Silicones. Stearyl alcohol. Arabinogalactan, Pol y vin y l acrylate, Polyacrylic acid.

10. REASONS FOR MICROENCAPSULATION To protect reactive substances from the environment, To convert liquid active components into a dry solid system, To separate incompatible components for functional reasons, To protect the immediate environment of the microcapsules from the active components. Isolation of core from its surroundings, as in isolating vitamins from the deteriorating effects of oxygen. R etarding evaporation of a volatile core. Improving the handling properties of a sticky material .

11. REASONS FOR MICROENCAPSULATION CONT…. For safe handling of the toxic materials. T o get targeted release of the drug To control release of the active components for delayed (timed) release or long-acting (sustained) release, The problem may be as simple as masking the taste or odor of the core, To Increase of bioavailability, To produce a targeted drug delivery, Protects the GIT from irritant effects of the drug, Extension of duration of activity for an equal level of active agent .

12. Microencapsulation Physical or Physico -mechanical Physico -chemical Chemical Air suspension Centrifugal extrusion Pan coating Spray-drying Co-current Counter-current Mixed-flow Vibrational nozzle Ionotropic gelation Coacervation Solvent evaporation Polymerization Interfacial polymer In-situ polymerization Matrix polymer Classification of microencapsulation techniques

13. Air suspension Solid , particulate core materials are dispersed in a supporting air stream The coating material is sprayed on the air suspended particles Within the coating chamber, particles are suspended on an upward moving air stream The design of the chamber and its operating parameters effect a recirculating flow of the particles through the coating zone portion of the chamber, where a coating material, usually a polymer solution, is spray applied to the moving particles.

14. Air suspension  During each pass through the coating zone, the core material receives an increment of coating material. The cyclic process is repeated, perhaps several hundred times during processing, depending on: -  the purpose of microencapsulation - the coating thickness desired - Until the core material particles are thoroughly encapsulated.

15. Air suspension  The supporting air stream also serves to dry the product while it is being encapsulated Schematics of a fluid-bed coater. ( a) Top spray; ( b) bottom spray; ( c) tangential spray  Drying rates are directly related to the volume temperature of the supporting air stream.

16. Pan coating Pan coating is a physical method of preparing microencapsulation and It can only be used for particles greater than 600 microns in diameter. Process of micro encapsulation by pan coating 1. Solid particles are mixed with a dry coating material. 2. The temperature is raised so that the coating material melts and encloses the core particles, and then is solidified by cooling. Or, the coating material can be gradually applied to core particles tumbling in a vessel rather than being wholly mixed with the core particles from the start of encapsulation.

17. Pan coating The particles are tumbled in a pan or other device while the coating material is applied slowly The coating is applied as a solution or as an atomized spray to the desired solid core material in the coating pan Usually, to remove the coating solvent, warm air is passed over the coated materials as the coatings are being applied in the coating pans. In some cases, final solvent removal is accomplished in drying oven.

18. Pan coating The variables that should be controlled in pan coating : Pan speed : Pan speeds of 10 to 15 rpm are commonly used in nonaqueous film coating. Speeds that are too slow may cause over wetting resulting in stickiness and in high speed may cause rough appearance because less time of drying . Degree of atomization: The higher pressure of nozzles the higher degree of atomization thus spray droplets will be much smaller. The small droplets will dry before reaching the capsule beds as a result roughness occurs on capsule.

19. Pan coating Temperature : High coating chamber temperatures are conducive to rapid solvent evaporation and consequently to faster coating rate. Spray pattern : A spray pattern that is too narrow ,localized over wetting may result .

20. Spray drying & Spray-congealing Spray drying: The coating solidification is effected by rapid evaporating of solvent in which coating material is dissolved. Microencapsulation by spray-drying is a low-cost commercial process which is mostly used for the encapsulation of fragrances, oils and flavours . Steps: 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.

21. Spray-congealing The coating solidification is effected by thermally congealing a molten coating material. The removal of solvent is done by evaporation technique. This technique can be accomplished with spray drying equipment when the protective coating is applied as a melt. Steps: 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. -e.g. microencapsulation of vitamins with digestable waxes for taste masking

22. Spray drying & Spray-congealing Both process involve -Dispersing the core material in a liquefied coating substance/spraying or introducing the coating mixture on to core material. -Solidification of coating material. The principal difference between the two method is the means by which coating solidification is accomplished. Both process have advantages such as low bulk density product, porous nature capsules and free flowing particles.

23. 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 . eg . Evaluation of Sucrose Esters as Alternative Surfactants in Microencapsulation of Proteins by the Solvent Evaporation Method .

24. Solvent Evaporation process… Core material Dissolved Or Dispersed Coating polymer solution With Agitation Liquid Manufacturing Vehicle Phase Heating (If necessary) Evaporation of Polymer solvent Microencapsulation

25. SOLVENT EVAPORATIONS

26. SOLVENT EVAPORATIONS

27. SOLVENT EVAPORATIONS

28. Pharmaceutical Application To improve the flow properties. e.g. Thiamine, Riboflavin To enhance the stability. e.g. Vitamins To reduce the volatility of materials. e.g. Peppermint oil, Methyl salicylate To avoid incompatibilities. e.g. Aspirin and Chloramphenicol To mask the unpleasant taste and odour . e.g. Aminophylline, castor oil To convert liquids into solids. e.g. Castor oil, Eprazinone , To reduce gastric irritation. e.g. Nitrofurantoin , Indomethacin Microencapsulation has been employed to provide protection to the core materials against atmospheric effects, e.g., Vitamin A Palmitate .

29. 42 Polyme r izati o n A re l a tiv e ly new m ic r o e ncapsul a tion m ethod u t i l izes poly m e riz a tion techniques to from protective microcapsule coatings in situ. The method involve the reaction of monomeric unit located at the interface existing between a core material substance and continuous phase in which the core material is disperse. The core material supporting phase is usually a liquid or gas, and therefore polymerization reaction occur at liquid-liquid, liquid-gas, solid-liquid, or solid-gas interface. E.g. In the formation of polyamide (Nylon) polymeric reaction occurring at liquid-liquid interface existing between aliphatic diamine & dicarboxylic acid halide.

30. D rug Addition of the alcoholic solution of the initiator (e.g., AIBN) 8 hrs Reaction time Monomer(s) (e.g. acrylamide, methacrylic acid) + Cross-linker (e.g. methylenebisacrylamide) A l co h ol T (reaction) = 60 °C Nitrogen Atmosphere Preparation of the Polymerization Mixture Initiation of Polymerization Monodisoerse Latex Formation by Polymer Precipitation RECOVERY OF POLYMERIC MICROPARTICLES M o nodisper s e m i cro g els in t he micron or submicron size range. Precipitation polymerization starts from a homogeneous monomer solution in which the synthesized polymer is insoluble. The particle size of the resulting de p en d s o n the microspheres p o l y m er i zati o n including the c o n ditions, m o n o m e r/co monomer composition, the amount of initiator and the total monomer concentration. POLYMERIZATION:

31. Polymerization Interfacial polymer In In t e rfaci a l poly m e r i z a tio n , the two re a c tants i n a polycondensation meet at an interface and react rapidly. In-situ polymerization In a few microencapsulation processes, the dire c t poly m eriz a tion of a single m o no m er i s ca r ried o u t on the particle surface. e.g. Cellulose fibers are encapsulated in polyethylene while im m er sed i n dry toluen e . Usual deposi t ion rates are abo u t 0.5μm/min. Coating thickness ranges 0.2-75μm. 3) Matrix polymer In a n u m ber of p r oc e s s e s, a co r e m at e r i al i s i m bedded i n a polymeric matrix during formation of the particles. Prepa res m ic r ocapsu l es co n tai n ing p rot e in solu t io n s by incorporating the protein in the aqueous diamine phase. National Lead Corporation- utilizing polymerization techniques

32. Polymerization Single emulsion method 46

33. Double emulsion method 47

34. Coacervation

35. COACERVATION / PHASE SEPARATION Polymeric Membrane D rop l ets Homogeneous Polymer Solution C oacer v ate Droplets PHASE S E P A R ATIO N MEMBRANE FOR M ATIO N 1.Formation of three immiscible phase 2.Deposition of coating 3.Rigidization of coating.

36. 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. Percentage yield = Amount of microcapsule obtained / Theoretical Amount×100 Scanning electron microscopy Scanning electron photomicrographs of drug loaded ethyl cellulose microcapsules were taken. A small amount of microcapsules was spread on gold stub and was placed in the scanning electron microscopy (SEM) chamber. The SEM photomicrographs was taken at the acceleration voltage of 20 KV. EVALUATION OF MICROCAPSULES

37. Particle size analysis For size distribution analysis, different sizes in a batch were separated by sieving by using a set of standard sieves. The amounts retained on different sieves were weighed . Encapsulation efficiency Encapsulation efficiency was calculated using the formula: Encapsulation efficiency = Actual Drug Content / Theoretical Drug Content ×100

38. Cefotaxime sodium drug content in the microcapsules was calculated by UV spectrophotometric method . The method was validated for linearity, accuracy and precision. A sample of microcapsules equivalent to 100 mg was dissolved in 25 ml ethanol and the volume was adjusted upto 100 ml using phosphate buffer of pH 7.4. The solution was filtered through Whatman filter paper . Then the filtrate was assayed for drug content by measuring the absorbance at 254 nm after suitable dilution. Estimation of Drug Content

39. Drug release was studied by using USP type II dissolution test apparatus (Electrolab TDT 08L) in Phosphate buffer of pH 7.4 (900 ml). The paddle speed at 100 rpm and bath temperature at 37 ± 0.5°c were maintained through out the experiment. A sample of microcapsules equivalent to 100 mg of cefotaxime sodium was used in each test. Aliquot equal to 5ml of dissolution medium was withdrawn at specific time interval and replaced with fresh medium to maintain sink condition. Sample was filtered through Whatman No. 1 filter paper and after suitable dilution with medium; the absorbance was determined by UV spectrophotometer (Elico SL159) at 254 nm. All studies were conducted in triplicate (n=3). The release of drug from marketed sustained release tablet was also studied to compare with release from microcapsules. Invitro Drug release Studies

40. A P P L IC A TION OF MIC R O E N C A P S U L A TION T E C H NI Q U E S

41. Applications of Microcapsules 1. Agricultural Applications Reduce insect populations by disrupting their mating process. Protects the pheromone from oxidation and light during storage and release . 2. Catalysis Safe handling, easy recovery, reuse and disposal at an acceptable economic cost. Metal species such as palladium (II) acetate and osmium tetroxide have been encapsulated in polyurea microcapsules and used successfully as recoverable and reusable catalysts without significant leaching and loss of activity.

42. 3. Food Industry Adding ingredients to food products to improve nutritional value can compromise their taste, colour, texture and aroma. Sometimes they slowly degrade and lose their activity, or become hazardous by oxidation reactions. Ing r e d ients can a l so r e a c t w i th co m ponen t s pre se n t i n t h e food system, which may limit bioavailability. 4. Pharmaceutical Applications Potential applications of this drug delivery system are replacement of therapeutic agents (not taken orally today like insulin), gene therapy and in use of vaccines for treating AIDS, tumors, cancer and diabetes. The delivery of corrective gene sequences in the form of plasmid DNA could provide convenient therapy for a number of genetic diseases such as cystic fibrosis and hemophilia.

43. Lupin has already launched in the market worlds first Cephalexin (Ceff-ER) and Cefadroxil (Odoxil OD) antibiotic tablets for treatment of bacterial infections. Aspirin controlled release version ZORprin CR tablets are used for relieving arthritis symptoms. Quinidine gluconate CR tablets are used for treating and preventing abnormal heart rhythms. Niaspan CR tablet is used for improving cholesterol levels and thus reducing the risk for a heart attack. Some of the applications of microencapsulation can be described in detail as given below: Prolonged release dosage forms. selectively Prepare enteric-coated dosage forms absorbed in the intestine rather than the stomach. It can be used to mask the taste of bitter drugs. To reduce gastric irritation. Pharmaceutical Applications

44. Used to aid in the addition of oily medicines to tableted dosage forms. To overcome problems inherent in producing tablets from otherwise tacky granulations. This was accomplished through improved flow properties. eg. The non-flowable multicomponent solid mixture of niacin, riboflavin, and thiamine hydrochloride and iron phosphate may be encapsulated and made directly into tablets. To protect drugs from environmental hazards such as humidity, light, oxygen or heat. eg. vitamin A and K have been shown to be protected from moisture and oxygen through microencapsulation. The separations of incompatible substances, eg. pharmaceutical eutectics . The stability enhancement of incompatible aspir i n - chlorpheniramine maleate mixture was acco m p l ished by microencapsulating both of them before mixing. Pharmaceutical Applications

45. Example of Some Microencapsulation

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