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Microencapsulation SIDDANNA M BALAPGOL


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Microencapsulation SIDDANNA M BALAPGOL

  1. 1. shivakumar kottam institute of pharmacy, A.P shivakumar kottam institute of pharmacy, A.P MICROENCAPSULATION
  2. 2.  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.  The product obtained by this process is called as micro particles, microcapsules.  Particles having diameter between 3 - 800µm are known as micro particles or microcapsules or microspheres. INTRODUCTION
  3. 3. CLASSIFICATION OF MICROPARTICLE Generally Micro particles consist of two components a) Core material b) Coat or wall or shell material. 1.Microcapsules: The active agent forms a core surrounded by an inert diffusion barrier. 2.Microspheres: The active agent is dispersed or dissolved in an inert polymer.
  4. 4. ADVANTAGES:  To Increase of bioavailability  To alter the drug release  To improve the patient’s compliance  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 core material.  To convert liquid to solid form & To mask the core taste.
  5. 5. FUNDAMENTAL CONSIDERATION: Core material Coating material Vehicle Solid Liquid Microencapsulation Polymers Waxes Aqueous Nonaqueous Resins Proteins Polysaccharides
  7. 7. Medicine & Pharmacy & vetinary Control release, Taste masking Vectorisation Artificial organs single dose treatment Medicine & Pharmacy & vetinary Control release, Taste masking Vectorisation Artificial organs single dose treatment Microencapsulation : Applications Chemistry Printing & recording Carbonless paper, Adhesives Pigments and Fillers Catalysts Food & feed Aromas, Probiotics Unsaturated oil, Enzyme food processing amino acid for cows Agriculture Fungicide – herbicide, Insect repellent, Biopesticide Pigments and fillers Artificial insemination Biotechnology & environment Continuous reactor, Shear protection, Reactor oxygenation Consumer & diversified Cosmetics, detergents (enzymes), sanitary (active, aromas)
  9. 9. MICROENCAPSULATION TECHNIQUES: 1. Air suspension techniques( Wurster) 2. Coacervation process 3. Spray drying & congealing 4. Pan coating 5. Solvent evaporation 6. Polymerization 7. Extrusion 8. Single & double emulsion techniques 9. Supercritical fluid anti solvent method (SAS) 10. Nozzle vibration technology
  10. 10. Microencapsulation by air suspension technique consist of the dispersing of solid, particulate core materials in a supporting air stream and the spray coating 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 recalculating 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. Air Suspension Techniques( Wurster)
  11. 11. 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 or whether the core material particles are thoroughly encapsulated. The supporting air stream also serves to dry the product while it is being encapsulated. Drying rates are directly related to the volume temperature of the supporting air stream.
  12. 12. Air suspension techniques (WURSTER PROCESS):
  13. 13. Coacervation process Formation of three immiscible phases; a liquid manufacturing phase, a core material phase and a coating material phase.  Deposition of the liquid polymer coating on the core material.  Rigidizing the coating usually by thermal, cross linking or desolvation techniques to form a microcapsule. In step 2, the deposition of the liquid polymer around the interface formed between the core material and the liquid vehicle phase. In many cases physical or chemical changes in the coating polymer solution can be induced so that phase separation of the polymer will occur.
  14. 14. Droplets of concentrated polymer solution will form and coalesce to yield a two phase liquid-liquid system. In cases in which the coating material is an immiscible polymer of insoluble liquid polymer it may be added directly. Also monomers can be dissolved in the liquid vehicle phase and subsequently polymerized at interface. Equipment required for microencapsulation this method is relatively simple; it consists mainly of jacketed tank with variable speed agitator.
  15. 15. COACERVATION / PHASE SEPARATION Polymeric Membrane Droplets Homogeneous Polymer Solution Coacervate Droplets PHASE SEPARATION MEMBRANE FORMATION 1.Formation of three immiscible phase 2.Deposition of coating 3.Rigidization of coating.
  17. 17. Spray-Drying & spray-congealing : - Microencapsulation by spray-drying is a low-cost commercial process which is mostly used for the encapsulation of fragrances, oils and flavors. Steps: 1- Core particles are dispersed in a polymer solution and sprayed into a hot chamber. 2- The shell material solidifies onto the core particles as the solvent evaporates. - The microcapsules obtained are of polynuclear or matrix type. Spray-Drying & spray-congealing
  18. 18. Spray-congealing: -This technique can be accomplished with spray drying equipment when the protective coating is applied as a melt. 1- the core material is dispersed in a coating material melt. 2- Coating solidification (and microencapsulation) is accomplished by spraying the hot mixture into a cool air stream. - e.g. microencapsulation of vitamins with digestible waxes for taste masking. Spray-congealing
  19. 19. Spray-Drying
  20. 20. SPRAY DRYING & CONGEALING ( COOLING) Spray drying : spray = aqueous solution / Hot air Spray congealing : spray = hot melt/cold air
  21. 21. 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.
  22. 22. The Southwest Research Institute (SWRI) has developed a mechanical process for producing microcapsules that utilizes centrifugal forces to hurl a core material particle trough an enveloping microencapsulation membrane thereby effecting mechanical microencapsulation. Processing variables include the rotational speed of the cylinder, the flow rate of the core and coating materials, the concentration and viscosity and surface tension of the core material. The multiorifice-centrifugal process is capable for microencapsulating liquids and solids of varied size ranges, with diverse coating materials. The encapsulated product can be supplied as slurry in the hardening media or s a dry powder. Production rates of 50 to 75 pounds per our have been achieved with the process. MULTIORIFIC-CENTRIFUGAL PROCESS
  23. 23. A relatively new microencapsulation method utilizes polymerization techniques to from protective microcapsule coatings in situ. The methods involve 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. The continuous or core material supporting phase is usually a liquid or gas, and therefore the polymerization reaction occurs at a liquidliquid, liquid-gas, solid-liquid, or solid-gas interface. POLYMERIZATION
  24. 24. Drug 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) Alcohol T (reaction) = 60 °C Nitrogen Atmosphere Preparation of the Polymerization Mixture Initiation of Polymerization Monodisoerse Latex Formation by Polymer Precipitation RECOVERY OF POLYMERIC MICROPARTICLES Monodisperse microgels in the 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 microspheres depends on the polymerization conditions, including the monomer/co monomer composition, the amount of initiator and the total monomer concentration. POLYMERIZATION:
  25. 25. 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 [7]. 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
  26. 26. 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 [5]. Encapsulation efficiency [8] Encapsulation efficiency was calculated using the formula: Encapsulation efficiency = Actual Drug Content / Theoretical Drug Content ×100
  27. 27. Cefotaxime sodium drug content in the microcapsules was calculated by UV spectrophotometric (Elico SL159 Mumbai India) 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 [9]. Estimation of Drug Content
  28. 28. 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
  29. 29. To study the mechanism of drug release from the cefotaxime sodium microcapsules, the release data were fitted to the following equations: (Time in each case was measured in minutes) KINETIC ANALYSIS OF DISSOLUTION DATA Model 1. Zero order kinetics Q1==Q0 + Kot Where, Q1-amount of drug dissolved in time t Q0-initial amount of drug in the solution K0-zero order release constant Model 2. First order kinetics Ln Qr = ln Q0K1t Where, K1--first order release constant Q0-initial amount of drug in the solution Q1-amount of drug dissolved in time t
  30. 30. Model 3.Higuchi model Q= tDCs (2c-Cs) Where, Q- Amount of drug release in time t C- Initial drug concentration Cs- drug solubility in the matrix D- Diffusion constant of the drug molecule in that liquid Model 5.Korsmeyer-Peppas Mt M∞ = atn Where, a- constant incorporating structural and geometric characteristics of the drug dosage form n- the release exponent (indicative of the drug release mechanism) Mt/M∞- fractional release of drug.