Microencapsulation ndds roll no.01
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This document discusses microspheres, which are small spherical particles used to deliver drugs in a sustained or controlled release manner. It defines microspheres and notes their sizes can range from 50nm to 2mm. The document outlines the prerequisites for ideal microparticle carriers and various polymers that can be used in microsphere preparation. It also describes common microsphere manufacturing methods like single emulsion, double emulsion, solvent evaporation, spray drying, and the BRACE process. The mechanisms of drug release from microspheres and their advantages for drug delivery are summarized.
Microencapsulation ndds roll no.01
- 1. MICROSPHERESMICROSPHERES Presented by, Hinglajia Hetal Ratilal M.Pharm- Pharmaceutics, Sem-II 14024671001 SKPCPER, Ganpat University, Kherwa Guided by, Dr. R. P. Patel
- 2. INTRODUCTION • The oral route is considered as the most promising route of drug delivery. Conventional drug delivery system achieves as well as maintains the drug concentration within the therapeutically effective range needed for treatment, only when taken several times a day. • This results in a significant fluctuation in drug levels. A well defined controlled drug delivery system can overcome some of the problems of conventional therapy and enhance the therapeutic efficacy of a given drug.. • There are various approaches in delivering a therapeutic susbstance to the target site in sustained controlled release fashion using microspheres as carrier for drug • Administration of drugs in the form of microspheres usually improves the treatment by providing the localization of the active substances at the site of action & by prolonging the release of drugs.
- 3. POTENTIAL USE OF MICROSPHERES IN THE PHARMACEUTICAL INDUSTRY • Taste and odor masking. • Conversion of oils and other liquids to solids for ease of handling. • Protection of drugs against the environment (moisture, light etc.). • Separation of incompatible materials (other drugs or excipients). • Improvement of flow of powders. • Aid in dispersion of water-insoluble substances in aqueous media, and Production of SR, CR, and targeted medications.
- 4. PREREQUISITES FOR IDEAL MICROPARTICULATE CARRIERS Longer duration of action Control of content release Increase of therapeutic efficacy Protection of drug Reduction of toxicity Biocompatibility Sterilizability Relative stability Water solubility or dispersibility Bioresorbability Targetability Polyvalent
- 5. DEFINITION OF MICROSPHERES • Microparticles or microspheres are defined as small, insoluble, free flowing spherical particles consisting of a polymer matrix and drug. and sized from about 50 nm to about 2 mm. • The term Nano spheres is often applied to the smaller spheres (sized 10 to 500 nm) to distinguish them from larger microspheres • Ideally, microspheres are completely spherical and homogeneous in size
- 6. • Microspheres are made from polymeric , waxy or protective materials that is biodegradable synthetic polymers and modified natural products. • Microspheres are manufactured in both solid and hollow form. Hollow microspheres are used as additives to lower the density of a material. • Solid biodegradable microspheres incorporating a drug dispersed or dissolved throughout particle matrix have the potential for controlled release of the drug. • These carriers received much attention not only for prolonged release but also for the targeting anti cancer drugs to the tumour.
- 7. TYPES OF MICROSPHERES • Microcapsule: consisting of an encapsulated core particle. Entrapped substance completely surrounded by a distinct capsule wall. • Micromatrix: Consisting of homogenous dispersion of active ingredient in particle. Microcapsule Micromatrix Types of Microspheres
- 8. POLYMERS USED IN THE MICROSPHERE PREPARATION Synthetic Polymers Non-biodegradable • PMMA - Poly(methyl methacrylate) • Acrolein • Epoxy polymers Biodegradable • Lactides and Glycolides copolymers • Polyalkyl cyanoacrylates • Polyanhydrides
- 9. • Natural Materials Proteins • Albumins • Gelatin • Collagen Carbohydrates • Starch agarose • Carrageenan • Chitosan Chemically modified carbohydrates • Poly(acryl)dextran • Poly(acryl)starch
- 10. ADVANTAGES • Controlled release for longer period of time (like 1-3 months). • Frequency is reduced and hence patient compliance is increased. • Constant release and hence no peaks and troughs in concentration of drug. • Low dose and hence toxic effect is less. • Targeting the tissue is possible. • Other organ toxicity is less. • No distribution through out the body (no dilution effect)
- 11. DISADVANTAGES • Intended mainly for parenteral route which causes pain. • Forms a depot in tissue or muscle for longer period and hence may produce pain when muscle activities are done. • Once administered, it is difficult to take back the dose. • Polymer may produce toxic effects. • High cost.
- 12. MECHANISMS OF DRUG RELEASE • Degradation controlled monolithic system. • Diffusion controlled monolithic system. • Erodible poly agent system.
- 13. DEGRADATION CONTROLLED MONOLITHIC SYSTEM. • The drug is dissolved in the matrix is in degradation controlled monolithic microspheres system, the dissolved and is released only on degradation of the matrix. • The diffusion of the drug is slow compared with the degradation of the matrix. • When degradation as by homogeneous bulk mechanism, drug release is show initially and increase rapidly when repaid bulk degradation starts. • Drug release from such type of device in independent of the geometry of the device if the degradation is by homogeneous mechanism, degradation is confined to the surface. Hence rate of release is affected by the geometry of the device.
- 14. DIFFUSION CONTROLLED MONOLITHIC SYSTEM. • Here the active is released by diffusion prior to or concurrent with the degradation of the polymer matrix. • Degeneration of the polymer matrix affects the rate of release and to be taker into account. • Rate of release also depends on whether the polymer degrades by homogeneous or heterogeneous mechanism.
- 15. ERODIBLE POLY AGENT SYSTEM. • In this case the active agent is chemically attach to matrix & the rate of biodegradation of matrix is slow compared to the rate of hydrolysis of drug-polymer bond. • Assuming that the rate of diffusion of active agent from the matrix to the surrounding is rapid, the rate limiting step is the rate of cleavage of bond attaching drug to polymer matrix. • In vitro studies in rats using labeled drug polymer conjugate showed that a fairly constant release is obtained during the time of observation which was 5 months
- 16. MICROSPHERE MANUFACTURE • Most important physicochemical characteristics that may be controlled in microsphere manufacture are: Particle size and distribution Polymer molecular weight Ratio of drug to polymer Total mass of drug and polymer
- 17. GENERAL METHODS OF PREPARATION • Single Emulsion techniques • Double emulsion techniques • Polymerization techniques - Normal polymerization. - Interfacial polymerization • Coacervation phase separation techniques • Emulsification-solvent evaporation method • Spray drying and spray congealing • Brace process
- 18. SINGLE EMULSION BASED METHOD Aq.Solution/suspension of polymer Dispersion in organic phase (Oil/Chloroform) Microspheres in organic phase Microspheres in organic phase MICROSPHERES Stirring, Sonication CROSS LINKING Chemical cross linking (Glutaraldehyde/Formald ehyde/ButanolHeat denaturation Centrifugation, Washing, Separation
- 19. Aq.Solution of protein/polymer First emulsion (W/O) MICROSPHERES Dispersion in oil/organic phase Homogenization Separation, Washing, Drying Addition of aq. Solution of PVA Addition to large aq. Phase Denaturation/hardening Multiple emulsion Microspheres in solution DOUBLE EMULSION BASED METHOD
- 21. INTERFACIAL POLYMERIZATION TECHNIQUE • When two reactive monomers are dissolved in immiscible solvents, the monomers diffuse to the oil- water interface where they react to form a polymeric membrane that envelopes dispersed phase. • Drug is incorporated either by being dissolved in the polymerization medium or by adsorption onto the nanoparticles after polymerization completed. • The nanoparticle suspension is then purified to remove various stabilizers and surfactants employed for polymerization by ultracentrifugation and re- suspending the particles in an isotonic surfactant-free medium.
- 22. PHASE SEPARATION METHOD Aqueous/Organic.Solution of polymer Drug dispersed or dissolved in polymer solution MICROSPHERES Drug Separation, Washing, Drying Hardening Polymer rich globules Microspheres in aq./organic phase
- 23. SALTING-OUT PROCESS • An aqueous phase saturated with electrolytes (e.g., magnesium acetate, magnesium chloride) and containing PVA as a stabilizing and viscosity increasing agent is added under vigorous stirring to an acetone solution of polymer. • In this system, the miscibility of both phases is prevented by the saturation of the aqueous phase with electrolytes, according to a salting-out phenomenon. • The addition of the aqueous phase is continued until a phase inversion occurs and an o/w emulsion is formed
- 25. SPRAY DRYING AND SPRAY CONGEALING METHOD • These methods are based on drying of the mist of polymer and drug in air. Depending on the removal of solvent or cooling the solution are named as “drying” and “congealing”, respectively. • The polymer dissolved in a suitable volatile organic solvent (dichloromethane,acetone,etc) • The drug in the solid form is then dissolved in polymer solution under high speed homogenization. • This dispersion is atomized in a stream of hot air. • This leads to formation of small droplets from which solvent evaporates leading to the formation of microspheres. • These are then separated from hot air by means of cyclone separator. • Spray congealing involves the formation of microspheres by solidifying the melted mass of drug and polymer in the form of minute particles.
- 26. Ultra Spherical Microspheres.. Microspheres with a monodisperse grain size distribution and the smallest divergence are manufactured by BRACE. • Perfectly spherical Microspheres • Monodisperse grain size, narrow size distribution with diameters between 50µm and 5000µm • Nonabrading, therefore dust-free • Free flowing, porous, large surface area,soft or rigid The BRACE-Process
- 27. THE BRACE-PROCESS A liquid is gently pumped through a vibrating nozzle system whereupon exiting the fluid stream breaks up into uniform droplets. The surface tension of these droplets moulds them into perfect spheres in which gelation is induced during a short period of free fall. Solidification can be induced in a gaseous and/or liquid medium through cooling, drying, or chemical reaction. There are no constraints on the type of liquid—molten materials, solutions, dispersions, sols, or suspensions can be used to manufacture perfectly spherical Microspheres.
- 28. CONCLUSION The concept of microsphere drug delivery systems offers certain advantages over the conventional drug delivery systems such as controlled and sustained delivery. Apart from that microspheres also allow drug targeting to various systems such as ocular , intranasal , oral and IV route . Novel technologies like magnetic microspheres, immunomicrospheres offer great advantages and uses than conventional technologies.
- 29. Further more in future by combining various other strategies, microspheres will find the central place in novel drug delivery, particularly in diseased cellsorting ,diagnostics, gene and genetic materials, safe,targated and effective invivo delivery which may have implications in gene therapy. This area of novel drug delivery has innumerable applications and there is a need for more research to be done in this area.
- 30. REFERENCES S.P.Vyas., R.K.Khar, International Journal for Targeted & Controlled Drug Delivery Novel Carrier Systems., First Edition :2002.,Reprint :2007 page no:417,453. Review: Radioactive Microspheres for Medical Applications. International journal of Pharmaceutics 282 (2004) 1-18,Review polymer microspheres for controlled drug release. N.K.Jain ,Controlled and novel drug delivery edited by reprint 2007 pg.no.236-255. Donald L.Wise, Handbook of pharmaceutical controlled release technology. James Swarbrick, James C.Boylan ,Encyclopedia of pharmaceutical technology Editors, volume-10. Patrick B.Deasy, Microencapsulation and related drug delivery processes edited by. James Swarbrick, Encyclopedia of pharmaceutical technology , 3rd edition volume-4 . www.koboproducts.com www.brace.com www.wikipedia.org info@polysciences.com www.harperintl.com. www.pharmacy2011foru.blogspot.com
- 31. Donald L.Wise, Handbook of pharmaceutical controlled release technology. James Swarbrick, James C.Boylan ,Encyclopedia of pharmaceutical technology Editors, volume-10. Patrick B.Deasy, Microencapsulation and related drug delivery processes edited by. James Swarbrick, Encyclopedia of pharmaceutical technology , 3rd edition volume-4 . www.koboproducts.com www.brace.com www.wikipedia.org info@polysciences.com www.harperintl.com. www.pharmacy2011foru.blogspot.com