Microspheres & Microcapsules Pradip Sontakke

Microspheres & Microcapsules

1. MICROENCAPSULATION Presented By: Mr. Pradip F. Sontakke Assistant professor Dept. of Pharmaceutics SHREE SAMBHAJI COLLEGE OF PHARMACY KHADKUT , NANDED .

2. 2 INTRODUCTION Microencapsulation is a process used to enclose tiny particles or droplets within a coating to form small capsules. These capsules can contain active ingredients, such as drugs, nutrients, flavors, or other substances, and the coating protects the contents from the external environment, controls the release of the encapsulated material, or improves the stability and shelf life of the core substance. Key Aspects of Microencapsulation Core Material : The substance that is encapsulated. Coating Material : The material used to form the capsule around the core. Encapsulation Methods : Various techniques are used for microencapsulation .

3. Microspheres are solid spherical particles ranging in size from 1-1000µm. They are spherical free flowing powders consisting of proteins or synthetic polymers, which are biodegradable in nature. It is reliable means to deliver the drug to the target site with specificity, if modified and to maintain the desired concentration at the site of interest. There are two types of microspheres 1) Microcapsules. 2 )Micr o m a trice s . Microcapsule Micro m atrix Fig: Microspheres 3

4. MICROSPHERES- The spherical shells of microspheres are usually made up of polymers which are having a diameter in microns or nanometer range, and it is often filled with a drug substance for release as the shell is degraded. 4

5. CLASSIFICATION: Microspheres Microcapsules Micrometrics Microcapsules are those in which entrapped substance is distinctly surrounded by distinct capsule wall. Micrometrics in which entrapped substance is dispersed throughout the matrix. Microencapsulation is a process in which applying relatively thin coating to small particles of solid or droplets of liquids and dispersions. Synonyms: Microcapsules Microsphers Coated granules Pellets Seeds Microsperules Spansules 5

6. Generally Micro particles consist of two components Core material Coat or wall or shell material . Microcapsules : micrometric reservoir systems Microspheres : micrometric matrix systems 6

7. Fig: Microspheres and Microcapsules 7

8. ADVANTAGES : To increase bioavailability. To improve patient compliance. To produce targeted drug delivery. To reduce reactivity of the core in relation to the outside environment. To decrease evaporation rate of the core material.(Reduction of volatility) To convert liquid to solid form (e.g. Eprazinone ) To mask the taste of core material. 8

9. DISADVANTAGES: Formulation difficulties No single method of microencapsulation is applicable to all API material. Difficult to obtain continuous and uniform film. Inadequate stability or self life of sensitive drug material. Failure to produce predicted release. It is an expnsive process. Requires skills. 9

10. 10 Methods of microencapsulation

11. 11 Air suspension microencapsulation, also known as fluidized bed coating, is a technique where particles are suspended in an upward stream of air while a coating material is sprayed onto them. This method is extensively used in pharmaceuticals, food industries, agriculture, and other fields to encapsulate active ingredients, allowing for controlled release, protection from environmental factors, and improved handling. The Wurster process, also known as bottom-spray fluid bed coating, is a specific type of air suspension technique used in microencapsulation. It was developed by Dr. Dale E. Wurster in the 1950s. Process Preparation of Core Particles The material to be encapsulated (core particles) is prepared and sized appropriately. This material can be in the form of powders, granules, or small pellets. Air Suspension Technique

12. 12 Fluidization The core particles are placed in a fluidized bed chamber. A stream of air is carried from the bottom of the chamber, causing the particles to become suspended and behave like a fluid. This ensures that the particles are well separated and move freely within the chamber. Spraying of Coating Material A coating solution or suspension is sprayed onto the fluidized particles. The coating material can be a polymer, lipid, or any other suitable encapsulating agent. The spray nozzle can be positioned at various points (top-spray, bottom-spray, or lateral-spray ) depending on the desired coating characteristics and equipment design. Drying and Solidification As the coating material is sprayed onto the fluidized particles, it quickly dries and solidifies due to the continuous flow of air. This forms a uniform coating around each core particle Recycling of Air The air used for fluidization is usually recycled within the system, often passing through filters and heaters to maintain the desired temperature and cleanliness.

13. 13 Process Parameters Air Flow Rate : Must be optimized to achieve proper fluidization without causing excessive particle attrition or loss. Spray Rate: Should be controlled to ensure that the coating material is applied at a consistent rate without over-wetting the particles. Temperature: The air temperature should be high enough to dry the coating material quickly but not so high as to degrade the core material or the coating agent. Atomization Pressure: The pressure at which the coating solution is sprayed affects the droplet size and, consequently, the uniformity and quality of the coating. FIG :- Air Suspension Technique

14. 14 Advantages Uniform Coating: The cyclic movement of particles through the spray zone ensures a uniform and consistent coating. Controlled Release: The thickness and composition of the coating can be precisely controlled, allowing for tailored release profiles of the encapsulated material. High Efficiency: The process is efficient in terms of material usage and time, with minimal waste. Disadvantages Cost: The initial setup and operational costs can be high due to the need for specialized equipment. Complexity: Requires careful optimization and control of process parameters to achieve the desired coating quality. Heat Sensitivity: As with other fluid bed processes, the involvement of heated air might not be suitable for heat-sensitive materials.

15. 15 Oldest industrial procedures for forming small, coated particles or tablets. Solid particle greater than 600 micron size are generally consider for effective coating. It is used for preparation of controlled- release beads. Coating is applied as solution by atomized spray to desired solid core material in coating pan. Usually warm air is passed over the coated material as the coating are being applied in material as the coating pan. PAN COATING Fig .Pan coating

16. 16 IONOTROPIC GELATION TECHNIQUE Ionotropic gelation is a widely used technique in microencapsulation, particularly for encapsulating drugs, nutrients, and other bioactive compounds. Microencapsulation involves creating small capsules that can protect the core material and control its release. Process of Ionotropic Gelation Preparation of Polymer Solution: The process begins with dissolving a natural or synthetic polymer, such as alginate or chitosan, in an aqueous solution. The concentration of the polymer solution can vary depending on the desired properties of the microcapsules. Preparation of Core Material: The substance to be encapsulated (the core material) is prepared. This could be a drug, nutrient, enzyme, or other bioactive compounds. The core material is often dispersed or dissolved in the polymer solution.

17. 17 Formation of Droplets: The polymer solution containing the core material is then extruded or dropped into an ion solution using various techniques such as: Dropping: Using a syringe or a pipette. Spraying: Using a nozzle to create fine droplets. Electrospraying : Using an electric field to create fine droplets. Ionotropic Gelation: Upon contact with the ion solution (commonly a solution of divalent cations like calcium chloride for alginate), the droplets undergo immediate gelation. The ions diffuse into the polymer droplets, causing the polymer chains to cross-link and form a gel matrix around the core material, creating microcapsules. Hardening and Washing: The formed microcapsules are allowed to harden for a specific period to ensure complete gelation. They are then collected and washed to remove any unreacted ions and impurities.

18. 18 Drying : Depending on the application, the microcapsules can be dried using techniques such as freeze-drying or air-drying to enhance their stability and prolong shelf life. The counter ions used for ionotropic gelation can be divided in two major categories: Low molecular weight counter ions (e.g. CaCl ₂, BaCl 2 , MgCl 2 , CuCl 2 , ZnCl 2 , CoCl 2 , pyrophosphate, tripolyphosphate , tetrapolyphosphate , octapolyphosphate, hexameta - phosphate. High molecular weight ions (e.g. Octyl sulphate, lauryl sulphate, hexadecyl sulphate, cetylstearyl sulphate).

19. 19 Fig. Ionotropic gelation technique Advantages of Ionotropic Gelation Mild Conditions: The process typically occurs at room temperature and neutral pH, making it suitable for encapsulating sensitive bioactive compounds. Biocompatibility: The polymers used, such as alginate and chitosan, are generally biocompatible and non-toxic. Control Over Release: The release profile of the encapsulated material can be controlled by adjusting the polymer concentration, the type and concentration of ions, and the conditions of gelation.

20. The coacervation technique in microencapsulation involves the creation of small capsules that enclose an active ingredient (core material) within a polymeric shell. This method is widely used in pharmaceuticals, food technology, cosmetics, and agricultural products to protect sensitive ingredients, control release rates, and mask tastes or odour . Types of Coacervation Simple Coacervation: This method involves a single polymer. Coacervation is induced by changing the conditions of the solution, such as temperature, pH, or adding a nonsolvent, which causes the polymer to separate out of solution and form a coating around the core material. Complex Coacervation: This involves two or more polymers, typically with opposite charges (e.g., a protein and a polysaccharide). When these oppositely charged polymers are mixed under appropriate conditions, they interact to form a coacervate phase, which then encapsulates the core material. COACERVATION TECHNIQUE

21. 21 Steps in the Coacervation Process Preparation of Core Material: The active ingredient to be encapsulated is dispersed or dissolved in a liquid medium. This can be an aqueous or non-aqueous solution depending on the solubility of the core material. Preparation of Polymer Solution: Polymers are dissolved in a suitable solvent to form a solution. In complex coacervation, solutions of two different polymers (one positively charged and one negatively charged) are prepared separately. Mixing and Coacervation Induction: The core material and polymer solutions are mixed under controlled conditions. For simple coacervation, changes in temperature, pH, or the addition of a non-solvent induce coacervation. For complex coacervation, mixing the oppositely charged polymer solutions causes them to interact and form a coacervate phase around the core material. Coacervate Phase Separation: The coacervate droplets, which contain the core material, are allowed to separate out from the solution. This can be facilitated by gentle stirring and controlled cooling.

22. 22 Hardening of Microcapsules: The coacervate droplets are then hardened to form stable microcapsules. This can be done by various methods such as: Cross-linking: Using chemical cross-linking agents like glutaraldehyde to create covalent bonds between polymer chains, thus stabilizing the shell. Thermal Treatment: Heating the coacervate droplets to solidify the polymer shell. Desolvation: Removing the solvent to harden the polymer shell. Recovery and Drying: The formed microcapsules are separated from the suspension medium, typically by filtration or centrifugation. They are then washed to remove any residual free polymers and dried to obtain the final microencapsulated product.

23. 23 Applications of Coacervation-Based Microencapsulation Pharmaceuticals: Protecting drugs from degradation, controlling release rates, and targeting delivery to specific sites in the body. Food Industry: Encapsulation of flavors, vitamins, and probiotics to enhance stability and control release in the digestive system. Cosmetics: Encapsulation of active ingredients to improve stability, control release, and enhance product performance. Agriculture: Encapsulation of pesticides, fertilizers, and other agrochemicals to protect them from environmental degradation and control their release.

24. 24 Fig. Simple coacervation

25. 25 Fig. Complex coacervation

26. 26 The solvent evaporation method is a technique used to create solid particles or films from a solution containing a dissolved material in a volatile solvent. This method is widely used in the pharmaceutical, food, and materials science industries. 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. SOLVENT EVAPORATION METHOD Fig solvent evaporation method

27. 27 These are techniques where monomers undergo polymerization reactions in the presence of active ingredients to form a solid polymeric shell or matrix that encapsulates the active substances. The encapsulation can occur at the interface of two immiscible phases, within dispersed droplets, or throughout a continuous phase. POLYMERIZATION TECHNIQUES 1. Interfacial Polymerization Interfacial polymerization involves the reaction of monomers at the interface of two immiscible phases, typically an aqueous phase and an organic phase. This forms a polymeric shell around the core material. Process : Preparation : The core material is dispersed in an aqueous or organic phase. Addition of Monomers : Monomers are added to both phases. For example, an aqueous phase may contain a water-soluble monomer, and an organic phase may contain an oil-soluble monomer.

28. 28 Polymerization : The monomers react at the interface of the two phases to form a polymeric shell around the dispersed core material. Collection : The microcapsules are collected, washed, and dried. 2. In-Situ Polymerization In-situ polymerization involves the polymerization of monomers within the continuous phase, leading to the formation of a polymeric matrix around the core material. Process : Dissolution or Dispersion : The core material is dissolved or dispersed in a solution containing monomers and initiators. Polymerization : Polymerization is initiated by heat, light, or chemical initiators, leading to the formation of a polymeric network around the core material. Collection : The resulting microcapsules are separated, washed, and dried.

29. 29 3. Emulsion Polymerization Emulsion polymerization involves polymerizing monomers in an emulsion to form polymeric particles that encapsulate the core material. Process : Emulsification : Monomers, surfactants, and initiators are emulsified in water to form droplets. Polymerization : Polymerization occurs within the droplets, leading to the formation of polymeric microcapsules. Collection : The microcapsules are separated from the emulsion, washed, and dried. 4. Suspension Polymerization Suspension polymerization involves dispersing monomers in a continuous aqueous phase, with the polymerization occurring within the suspended droplets. Process : Suspension : The core material and monomers are suspended in water with stabilizers. Polymerization : Polymerization is initiated within the suspended droplets, forming polymeric microcapsules. Collection : The microcapsules are separated, washed, and dried.

30. 30 APPLICATION OF MICROENCAPSULATION

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