microsphere and microencapsulation
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This document discusses microspheres and microencapsulation. It was submitted by Debasish Deka for his M. Pharm degree under the guidance of Ananta Choudhury. It covers the introduction, advantages, limitations, types (e.g. bioadhesive, magnetic, floating), methods of preparation (e.g. solvent evaporation, spray drying), evaluation, and applications of microspheres in pharmaceutical industry (e.g. buccal drug delivery, intratumoral delivery). Microencapsulation is also introduced as enclosing solids, liquids or gases in microscopic particles through thin coatings, with origins in the 1930s business machines industry.
microsphere and microencapsulation
- 1. SUBMITTED BY Debasish Deka M. Pharm Faculty of Pharmaceutical Science Assam down town University UNDER THE GUIDANCE OF Ananta Choudhury Associate Professor Faculty of Pharmaceutical Science Assam down town University
- 2. CONTENTS MICROSPHERE -INTRODUCTION -ADVANTAGES AND LIMITATION -TYPES OF MICROSPHERES -METHOD OF PREPARATION -EVALUATION OF MICROSPHERES -APPLICATION OF MICROSPHERES IN PHARMACEUTICAL INDUSTRY MICROCAPSULATION -INTRODUCTION -CHARATERIZATION OF MICROCAPSULATION -APPLICATION OF MICROCAPSULATION 2
- 4. INTRODUCTION A well designed controlled drug delivery system can overcome some of the problems of conventional therapy and enhance the therapeutic efficacy of a given drug. To obtain maximum therapeutic efficacy, it becomes necessary to deliver the agent to the target tissue in the optimal amount in the right period of time there by causing little toxicity and minimal side effects. 4
- 5. 5 There are various approaches in delivering a therapeutic substance to the target site in a sustained controlled release. One such approach hoi nkiis using microspheres as carriers for drugs. Microspheres are characteristically free flowing powders consisting of proteins or synthetic polymers which are biodegradable in nature and ideally having a particle size less than 200 µm. Microspheres used usually are polymers. They are classified into two types: 1)Natural Polymer 2)Synthetic Polymer
- 6. Natural polymers Synthetic Polymers carbohydrates proteins chemically modified Carbohydrates Biodegradable polymer Non Biodegradable polymerAgarose Gelatin Poly starch Glycolides Epoxypolymer Polymer 6
- 7. ADVANTAGES 1.Microspheres provide constant and prolonged therapeutic effect. 2.Reduces the dosing frequency and thereby improve the patient compliance. 3.They could be injected into the body due to the spherical shape and smaller size. 4.Provide constant and prolonged therapeutic effect. 5.Provide constant drug concentration in blood there by increasing patent compliance. 6.Convert liquid to solid form & to mask the bitter taste. 7.Protects the GIT from irritant effects of the drug. . 5
- 8. 8 LIMITATION Some of the disadvantages were found to be as follows 1.The modified release from the formulations. 2.Differences in the release rate from one dose to another. 3.Dosage forms of this kind should not be crushed. 4.The costs of the materials and processing of the controlled release preparation, are substantially higher than those of standard formulations. 5.Process conditions like change in temperature, pH, solvent addition, and evaporation/agitation may influence the stability of core particles to be encapsulated.
- 10. 1.Bioadhesive microspheres: Adhesion can be defined as sticking of drug to the membrane by using the sticking property of the water soluble polymers. Adhesion of drug delivery device to the mucosal membrane such as buccal, ocular, rectal, nasal etc. can be termed as bio adhesion. These kinds of microspheres exhibit a prolonged residence time at the site of application and causes intimate contact with the absorption site and produces better therapeutic action. 10
- 11. 11 2. Magnetic microspheres: This kind of delivery system is very much important which localises the drug to the disease site. In this larger amount of freely circulating drug can be replaced by smaller amount of magnetically targeted drug. Magnetic carriers receive magnetic responses to a magnetic field from incorporated materials that are used for magnetic microspheres are chitosan, dextran etc. The different types are a. Therapeutic magnetic microspheres used to deliver chemotherapeutic agent to liver tumour. Drugs like proteins and peptides can also be targeted through this system. b. Diagnostic microspheres, used for imaging liver metastases.
- 12. 12 4. Radioactive microspheres: Radio embolization therapy microspheres sized 10-30 nm are of larger than the diameter of the capillaries and gets tapped in first capillary bed when they come across. They are injected in the arteries that leads them to tumour of interest so all these conditions radioactive microspheres deliver high radiation dose to the targeted areas without damaging the normal surrounding tissues. 3. Floating microspheres: It reduces chances of dose dumping. It produces prolonged therapeutic effect and therefore reduces dosing frequencies. Drug (ketoprofen) is given in the form of floating microspheres.
- 13. 13 5. Polymeric microspheres: The different types of polymeric microspheres can be classified as follows and they are A) Biodegradable polymeric microspheres B) Synthetic polymeric microspheres.
- 14. METHOD OF PREPARATION: 1. Spray Drying 2. Solvent Evaporation 3. Single emulsion technique 4. Double emulsion technique 5. Spray drying and spray congealing 6. Solvent extraction Spray Drying 14
- 15. 15 Dissolved in a suitable volatile organic solvent such as dichloromethane, Acetone, etc. Then dispersed in the polymer solution under high-speed homogenization Then atomized in a stream of hot air. Formation of the small droplets solvent evaporate Formation of the microspheres in a size range 1-100μm Micro particles are separated from the hot air by means of the cyclone separator while the trace of solvent is removed by vacuum drying
- 16. 16 This process is carried out in a liquid manufacturing vehicle phase. The microcapsule coating is dispersed in a volatile solvent which is immiscible with the liquid manufacturing vehicle phase. A core material to be microencapsulated is dissolved or dispersed in the coating polymer solution. With agitation the core material mixture is dispersed in the liquid manufacturing vehicle phase to obtain the appropriate size microcapsule. The mixture is then heated if necessary to evaporate the solvent for the polymer of the core material is disperse in the polymer solution, polymer shrinks around the core. Solvent Evaporation
- 17. 17 If the core material is dissolved in the coating polymer solution, matrix – type microcapsules are formed .The core materials may be either water soluble or water in soluble materials. Solvent evaporation involves the formation of an emulsion between polymer solution and an immiscible continuous phase whether aqueous (o/w) or non-aqueous.
- 19. 19 Double emulsion technique Double emulsion method of microspheres preparation involves the formation of the multiple emulsions or the double emulsion of type w/o/w and is best suited to water soluble drugs, peptides, proteins and the vaccines. This method can be used with both the natural as well as synthetic polymers. Spray drying and spray congealing These methods are based on drying of the mist of the polymer and drug in the air. Depending on the removal of the solvent or cooling of the solution, the two processes are named spray drying and spray congealing.
- 20. 20
- 21. One of the major merits of the process is feasibility of process under aseptic conditions. Spray drying process is used to encapsulate various penicillins. Thiamine Mononitrate and sulpha ethylthiadizole are encapsulated in a composition of mono- and diglycerides of palmitic acid and stearic acid using spray congealing. Very rapid solvent evaporation, however leads to the formation of porous microparticles. 21
- 22. 22 Solvent extraction Solvent evaporation method is used for manufacturing of microparticles, involves removal of the organic phase by extraction of the or non aqueous solvent. This method involves water miscible organic solvents as isopropanol. Organic phase can be removed by extraction with water. This process decreases the hardening time for the microspheres.
- 23. EVALUATION OF MICROSPHERES: 1. Particle size and shape The most widely used procedures to visualize microparticles are conventional light microscopy (LM) and scanning electron microscopy (SEM). 2. Electron spectroscopy for chemical analysis: The surface chemistry of the microspheres can be determined by using the electron spectroscopy for chemical analysis (ESCA). 3. Density determination: The density of the microspheres can be measured by using a multi volume pycnometer. 4. Angle of contact: The angle of contact is measured to determine the wetting property of a micro particulate carrier. 23
- 24. 6. Drug entrapment efficiency: Drug entrapment efficiency can be calculated using following equation, % Entrapment = Actual content/Theoretical content x 100. 5. In vitro methods: Release studies for different type of microspheres are carried out by using different suitable dissolution media, mostly by rotating paddle apparatus (USP / BP). APPLICATION OF MICROSPHERES IN PHARMACEUTICAL INDUSTRY: 24 1.Buccal Drug Delivery: Polymer is an excellent polymer to be used for buccal delivery because it has muco / bioadhesive properties and can act as an absorption enhancer. Chitosan, Sodium alginate.
- 25. 25 2.Intratumoral and Local Drug Delivery: In order to deliver paclitaxel at the tumor site in therapeutically relevant concentration, polymer films are fabricated. Mixture of drug has promising potential for use in controlled delivery in the oral cavity e.g. Gelatin, PLGA, Chitosan. 3.Gastrointestinal Drug Delivery: Polymer granules having internal cavities prepared by de acidification when added to acidic and neutral media are found buoyant and provided a controlled release of the drug e.g. Eudragit, Ethyl cellulose + Carbopol BSA, Gelatin. 4.Transdermal Drug Delivery: Polymer has good film- forming properties. The drug release from the devices is affected by the membrane thickness and cross-linking of the film. e.g. Chitosan, Alginate, PLGA.
- 27. Microencapsulation is a process by which solids, liquids or even gases may be enclosed in microscopic particles formation of thin coatings of wall material around the substances. The process had its origin in the late 1930s as a cleaner substitute for carbon paper and carbon ribbons as sought by the business machines industry. The ultimate development in the 1950s of reproduction paper and ribbons that contained dyes in tiny gelatin capsules released on impact by a typewriter key or the pressure of a pen or pencil was the stimulus for the development of a host of microencapsulated materials, including drugs INTRODUCTION 27
- 28. 28 Microencapsulation provides the means of converting liquids to solids, of altering colloidal and surface properties, of providing environmental protection and of controlling the release characteristics or availability of coated materials. Fig. 1: Microencapsulation process
- 29. -This technique can be used for converting liquid drugs in a free flowing powder. - The drugs, which are sensitive to oxygen, moisture or light, can be stabilized by microencapsulation. - Vaporization of many volatile drugs e.g. methyl salicylate and peppermint oil can be prevented by microencapsulation. - Many drugs have been microencapsulated to reduce toxicity and GI irritation including ferrous sulphate and KCl.. - Toxic chemicals such as insecticides may be microencapsulated to reduce the possibility of sensitization of factorial person. - Bakan and Anderson reported that microencapsulated vitamin A palmitate had enhanced stability. 29
- 30. The reasons for microencapsulation The reasons for microencapsulation are countless. In some cases, the core must be isolated from its surroundings, as in isolating vitamins from the deteriorating effects of oxygen, retarding evaporation of a volatile core, improving the handling properties of a sticky material, or isolating a reactive core from chemical attack. In other cases, the objective is not to isolate the core completely but to control the rate at which it leaves the microcapsule, as in the controlled release of drugs or pesticides. The problem may be as simple as masking the taste or odor of the core. Microsphere & microcapsule 30
- 31. 31 COATING MATERIAL PROPERTIES 1. Stabilization of core material. 2. Inert toward active ingredients. 3. Controlled release under specific conditions. 4. Film-forming, pliable, tasteless, stable. 5. Non-hygroscopic, no high viscosity, economical. 6. Soluble in an aqueous media or solvent, or melting. 7. The coating can be flexible, brittle, hard, thin etc.
- 32. 32 Examples of coating materials: 1.Water soluble resins – Gelatin, Gum Arabic, Starch, Polyvinyl pyrrolidone,Carboxy methyl cellulose, Hydroxy ethyl cellulose, Methyl cellulose, Polyvinyl alcohol , Arabinogalactan, , Polyacrylic acid. 2.Water insoluble resins – Ethylcellulose, Polyethylene, Polymethacrylate, Polyamide(Nylon), Poly(Ethylene- Vinyl acetate), Cellulose nitrate, Silicones. 3.Waxes and lipids – Paraffin, Carnauba, Spermaceti, Beeswax, Stearic acid, Stearyl alcohol, Glyceryl stearates . 4. Enteric resins – Shellac, Cellulose acetate phthalate.
- 33. 33 CHARACTERIZATION OF MICROCAPSULE -Angle of contact The angle of contact is measured to determine the wetting property of a micro particulate carrier -Particle size The microparticle size can be determined by laser diffractometry using a Malvern Mastersizer X -Dissolution apparatus Standard USP or BP dissolution apparatus have been used to study in vitro release profiles using both rotating elements (paddle and basket) -Sieve analysis Separation of the microspheres into various size fractions can be determined by using a mechanical sieve shaker
- 34. APPLICATION 34 -Quality and safety in food, agricultural & environmental sectors. - Beverage production
- 35. 35 - Protection of liquid crystals. - Soil inoculation. - To mask the bitter taste of drugs like Paracetamol, Nitrofurantoin etc.
- 36. THANK YOU 36