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Coacervation Phase Separation Techniques
- 1. Coacervation Phase Separation BY- GARGI NANDA M. PHARM-1 (PT) ROLL NO. 01 GUIDED BY- MADAM KRUTIKA SAWANT
- 2. Overview Introduction Coacervation Phase Separation Techniques for Coacervation Modified Techniques for Coacervation Aqueous Phase Separation Organic Phase Separation Solvent Evaporation Polyelectrolyte Multilayer Hydrogel Phase Inversion Melt Dispersion 2
- 3. Introduction Micro-encapsulation is a process in which tiny particles or droplets are surrounded by a coating to give small capsules of many useful properties. It can also be used to enclose solids, liquids, or gases inside a micrometric wall made of hard or soft soluble film, in order to reduce dosing frequency and prevent the degradation of pharmaceuticals. 3
- 4. Microencapsulation Techniques Physicochemical Coacervation Phase Separation Polymer Incompatibility Ionotropic Gelation Physicomechanical Spray Drying Fluidized Bed Technology Pan Coating Spinning Disc Co-extrusion Chemical Interfacial Polymerisation In-situ Polymerisation 4
- 5. Coacervation Phase Separation Coacervation Phase Separation refers to partial desolvation of a homogeneous polymer solution into a polymer-rich phase (coacervate) and the poor polymer phase (coacervation medium). The term originated from the Latin ›acervus‹ , meaning “heap”. Coacervation involves the separation of a liquid phase of coating material from a polymeric solution and wrapping of that phase as a uniform layer around suspended core particles. 5
- 6. Steps of Coacervation Formation of three immiscible chemical phases Deposition of the coating Rigidization of the coating 6
- 8. Techniques Used for Coacervation Change In Temperature Incompatible Polymer Addition Non-solvent Addition Salt Addition Polymer- Polymer Interaction 8
- 9. Temperature Change Under proper polymer concentration, temperature and agitation, liquid polymer coalesce around dispersed core and form embryonic micro particles. 9
- 10. Incompatible Polymer Addition Usage of dissimilar polymer in common solvent can be done for preparation of micro particles. 10
- 11. Non-Solvent Addition Liquid, which is non- solvent for polymer, is used for coacervation. 11
- 12. Salt Addition Soluble inorganic salts are added to aqueous solutions of water soluble polymers for phase separation 12
- 13. Polymer Interaction Interaction of oppositely charged polyelectrolytes result in the formation of complex with reduced solubility that phase separation occurs. 13
- 14. Modified Techniques of Coacervation Aqueous Phase Separation Organic Phase Separation Solvent Evaporation Encapsulation by polyelectrolyte multilayer Hydrogel Microsphere Phase Inversion Melt Dispersion 14
- 15. Aqueous Phase Separation The term aqueous phase separation is often more simply described as "oil-in-water" microencapsulation. In this process the core material is the oil and it should be immiscible in the continuous phase, namely water. 15
- 17. Aqueous Phase Separation Example A commercial example of aqueous phase separation would be the microencapsulation of an oily flavour such as sour cream with a gelatine wall. These microcapsules would then be dispersed in a dry cake mix. The mechanism of release would be during the moist baking cycle of the cake, moist-heat causing the capsule walls to first swell and then rupture. 17
- 18. Organic Phase Separation The term organic phase separation' is sometimes more simply referred to as "water-in-oil" microencapsulation. In this case the polar core is dispersed into an oily or non-polar continuous medium. The wall material is then dissolved in this continuous medium. Process Comprises of: Providing an aqueous phase comprising a material to be encapsulated Creating an emulsion of said aqueous phase in a continuous organic liquid phase comprising one or more organic solvents and one or more surface active agents, wherein the emulsion comprises discrete droplets of the aqueous phase dispersed in the continuous phase organic liquid, there being formed thereby an interface between the discrete droplets of the aqueous phase and the continuous organic liquid phase 18
- 20. Organic Phase Separation Example Dissolve ethyl cellulose in cyclohexane at 50°C with continuing mixing. Cyclohexane is the oily, continuous phase and the ethyl cellulose will later form the coacervative wall. The temperature is elevated to 70°C over a period of 20 to 30 minutes. The core material is added and the temperature raised to 80°C and is held at that temperature for one hour. The system is allowed to cool rapidly to 20-40°C. 20
- 21. Solvent Evaporation Microcapsule formation by solvent evaporation/solvent extraction is very similar to suspension crosslinking, but in this case the polymer is usually hydrophobic polyester. It facilitates a controlled release of a drug, which has many clinical benefits. Water insoluble polymers are used as encapsulation matrix using this technique. Biodegradable polymer PLGA (poly (lactic-co-glycolic acid)) is frequently used as encapsulation material. 21
- 22. Solvent Evaporation Process Microspheres are washed and dried. Emulsion is constantly stirred till organic solvent evaporates, giving microspheres. Formed emulsion is added to large amount of water having emulsifier (PVA) to form multiple emulsion. Organic phase having polymer solution is added in solvents like chloroform with stirring. Aqueous solution of drug is prepared. 22
- 24. Encapsulation By Polyelectrolyte Multilayer Sequentially immerse a substrate in positively and negatively charged polyelectrolyte solutions in a cyclic procedure. Core shell particles with tailored size and properties are prepared using colloidal particles as the core material that serves as a template onto which multilayers are fabricated. Hollow capsules of organic, inorganic or hybrid particles can be obtained by dissolving the core material. This technique is both versatile and simple, with the multilayer film thickness being controlled precisely by varying the total number of layers deposited. In this way the final properties can be tuned. 24
- 26. Polyelectrolyte Multilayer Technique Example Glucose oxidase has been microencapsulated by alternate deposition of polyallylamine and polystyrene sulfonate layers. 26
- 27. Hydrogel Microspheres Hydrogels have been used in numerous biological technologies including gel electrophoresis and cell encapsulation. In cell encapsulation, the matrix material defines the extracellular environment and likely impacts cell viability, function, growth, and differentiation. The matrix may provide the required growth substrate for anchorage-dependent cells or the appropriate immobilization needed by suspension cells. Numerous hydrogels have been used for cell encapsulation 27
- 28. Hydrogel Microencapsulation Polymer (eg. Alginates) are dissolved in an aqueous solution. Active ingredient is suspended in the mixture. Through a precise device, extrusion is done to form microdroplets. Microdroplets fall into hardening bath that is slowly stirred. 28
- 30. Phase Inversion Phase inversion is a term used to describe the physical phenomena by which a polymer dissolved in a continuous phase solvent system inverts into a solid macromolecular network in which the polymer is the continuous phase. Phase inversion phenomenon have been applied to produce macro and microporous polymer membranes and hollow fibers used in gas separation, ultrafiltration, ion exchange, and reverse osmosis. 30
- 31. Phase Inversion Process Polymer solution undergoes transition from single phase homogenous solution to two phase mixture Micellar droplets serve as nucleation sites and coat with polymer At critical concentration of polymer, droplets precipitate and solidify. In favourable conditions, micelles coalesce and precipitate to form continuous polymer network 31
- 32. Melt Dispersion In this technique the coating material is melted by heating upto 80oC. The drug is suspended in it and then emulsified in water containing emulsifying agent at 80oC under stirring. Microcapsules are formed as the temperature of the system reaches to room temperature. 32
- 33. Melt Dispersion Technique 33
- 34. Reference Indian Journal of Research in Pharmacy and Biotechnology Volume 1(3) May-June 2013 Page 324 MICROENCAPSULATION TECHNOLOGY K.P.Sampath Kumar,Tejbe.Sk , Shameem Banu, P.Naga Lakshmi, D.Bhowmik International Journal of Pharma and Bio Sciences MICROENCAPSULATION: A REVIEW JYOTHI SRI.S, A.SEETHADEVI , K.SURIA PRABHA, P.MUTHUPRASANNA AND ,P.PAVITRA Microencapsulation Technology and Applications Rama Dubey, T.C. Shami and K.U. Bhasker Rao 34
- 35. Reference (Contd.) Internet Scientific Publications Microencapsulation Techniques, Factors Influencing Encapsulation Efficiency: A Review N Jyothi, M Prasanna, S Prabha, P Seetha Ramaiah, G Srawan, S Sakarka Indo Global Journal of Pharmaceutical Sciences, 2012; 2(1): 1-20 1 Microencapsulation – A Novel Approach in Drug Delivery: A Review Nitika Agnihotri, Ravinesh Mishra*, Chirag Goda, Manu Arora Stability of Hydrogels Used in Cell Encapsulation: An In Vitro Comparison of Alginate and Agarose Molly S. Shoichet,* Rebecca H. Li, Melissa L. White, and Shelley R. Winn 35
- 36. Reference (Contd.) The Theory and Practice of Industrial Pharmacy; Lachman and Leibermann; 3rd Edition www.authorstream.com en.wikipedia.org Patent US6143211; Google Patents Patent US6113935; GooglePatents 36
- 37. En d