PHT333-PT311 Pharmaceutical Dosage Form 3 Lecture (8) Fall 2024 PDF

Pharmaceutical Dosage Form 3 Lecture (8) 1 By the end of this lecture each student should gain complete understanding of : 1. the meaning and advantages of microencapsulation 2. types of microencapsulation 3. Manufacturing processes 4. releas...

Pharmaceutical Dosage Form 3 Lecture (8) 1 By the end of this lecture each student should gain complete understanding of : 1. the meaning and advantages of microencapsulation 2. types of microencapsulation 3. Manufacturing processes 4. release patterns of microencapsulated drugs 5. Applications of Microencapsulation Interactive learning methods Open discussion Video on slide 17 Online quiz 3  References http://www.ejpmr.com/admin/assets/article_issue/1519801331.pdf EUROPEAN JOURNAL OF PHARMACEUTICAL AND MEDICAL RESEARCH:- SJIF Review Article ISSN 2394-3211 EJPMR MICROENCAPSULATION TECHNIQUES IN PHARMACEUTICAL FORMULATION Ayush Garg1 *, Kapil Chhipa2 and Lalit Kumar3 1Dept. of Pharmaceutics, Pacific College of Pharmacy, Udaipur, 313024. http://iglobaljournal.com/wp-content/uploads/2012/05/1.-Nitika-Agnihotri-et-al- 2012.pdf 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 Institute of Pharmacy & Emerging Sciences, Baddi University of Emerging Sciences & Technology, Makhnumajra, Baddi, Distt. Solan, H.P-173205, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093624/ Res Pharm Sci. 2010 Jul-Dec; 5(2): 65–77. PMCID: PMC3093624 PMID: 21589795 Microencapsulation: A promising technique for controlled drug delivery M.N. Singh, K.S.Y. Hemant,* M. Ram, and H.G. Shivakumar https://www.ijptonline.com/wp-content/uploads/2009/10/2332-2346.pdf IMPORTANCE AND CHARACTERIZATION OF MICROENCAPSULATION TECHNIQUES IN PHARMACEUTICAL DOSAGE FORMS - A REVIEW B.V.Subbaiah*, B.Krishnamoorthy*, M.Muthukumaran. Montessori Siva Sivani Institute of Science & Technology- College of pharmacy, Mylavaram, Vijayawada, Andrapradesh-521230. https://www.researchgate.net/publication/257415662_Effect_of_process_co nditions_on_the_microencapsulation_of_coffee_oil_by_spray_drying. Effect of process conditions on the microencapsulation of coffee oil by spray drying, July 2012, Food and Bioproducts Processing 90(3):413–424  MICROENCAPSULATION Microencapsulation is the process by which tiny solid particles or droplets of liquid or even gases are coated with a continuous film of polymeric material to produce capsules in the micrometer to millimeter range; - micron (1–1000 μm), - sub-micron (100–1000 nm), - nanometer (1–100 nm).  ADVANTAGES ✓Storage stability (protection against chemical reactions, oxygen, light, humidity) (e.g Environmental protection) E.g: Vit.A Palmitate. ✓ Reduction or Control of hygroscopicity.E.g: NaCl. ✓Stable separation of incompatible substances (Aspirin and Chlorpheniramine maleate ). (core & coat) ✓ Enhancing of flowability. ✓ Reduction of dust and electrostatic charge for powders. ✓To mask the core taste or odour (Masking of bitter taste drugs. Eg: Ofloxacin.) ADVANTAGES ✓Converting liquids into solid substances (transform liquid food flavorings, such as coffee oil) Allow handling of liquids as solids. ✓To alter the drug release (Depot effect, targeted and time-delayed release of active ingredients) ✓ Improved shelf life due to preventing degradation reactions. ✓To improve the patient’s compliance (e.g. Microencapsulation of Metoprolol Tartrate into Chitosan for Improved Oral Administration and Patient Compliance) (sustained release) ✓To decrease evaporation rate of the core material. (Fixation of volatile compounds) (e.g. Methyl salicylate) ✓ To Enhance solubility, permeability, bioavailability  FUNDAMENTAL CONSIDERATION Microencapsulation Core material Coating material Vehicle Solid Liquid Polymers Aqueous Non-aqueous Waxes Resins Proteins Polysaccharides  A) Core Material: (active constituents( ▪ Specific material to be coated. ▪ It may be liquid or solid. Examples of core material Final Core Material Purpose Product Form Acetaminophen Taste masking Tablet Potassium chloride Reduces gastric irritation Capsule Isosorbide dinitrate Sustained Release Capsule B- Coating Materials: The coating material should be capable of:- ✓ Forming a film that is cohesive with the core material ✓ Chemically compatible and nonreactive with the core material ✓ Provide the desired coating properties, such as strength, flexibility, impermeability, optical properties, and stability. ✓ Soluble in aqueous or organic solvent ✓ Stabilize the core material ✓ Control drug release under specific condition -Generally hydrophilic polymers, or hydrophobic polymers or a combination of both are used for the microencapsulation process. Examples of coating materials 1. Water soluble resin Gelatin, Gum Arabic, Starch, Polyvinylpyrrolidone PVP, Carboxymethylcellulose CMC. 2. Water insoluble resins Ethylcellulose, Polyethylene, Polyamide (Nylon), Silicones. 3. Waxes and lipids Paraffin, Carnauba, Spermaceti, Beeswax, Stearic acid, Stearyl alcohol, Glyceryl stearates. 4. Enteric resins Shellac, Cellulose acetate phthalate  Microencapsulation Generally consist of two components a) Core, internal phase or fill b) Shell, Coat or membrane. 1. Microcapsules: The active agent forms a core surrounded by an inert diffusion barrier (core-shell structure) 2. Microspheres: The active agent is dispersed or dissolved in an inert polymer (matrix systems). Microcapsules can be classified into three basic categories according to their morphology. A.Mononuclear (core-shell) microcapsules contain the shell around the core. B.Poly-nuclear:- While poly nuclear capsules have many cores enclosed within the shell. C.Matrix types:- In matrix encapsulation, the core material is distributed homogeneously into the shell material. Preparation of microcapsules should satisfy certain criteria: ❑ The ability to incorporate reasonable or high concentrations of the drug. (high encapsulation efficacy) ❑ Stability of the preparation after synthesis with a clinically acceptable shelf life. ❑ Controlled particle size and dispersability of microparticles in aqueous vehicles ❑ Release of active reagent with a good control over a wide time scale. ❑ Biocompatibility, biodegradability and Susceptibility to chemical modification.  Microencapsulation preparation techniques Physical Methods Chemical Methods 1. Pan Coating 1. Interfacial polymerization 2. Air suspension techniques 2. In-situ polymerization (Wurster) 3. Matrix polymerization 3. Spray Drying & Congealing 4. Solvent Evaporation 5. Centrifugal Extrusion 6. Single & Double Emulsion Techniques 1. Pan coating It is used for forming small, coated particles or tablets. The particles are tumbled in a pan or other device while the coating material is applied slowly with respect to microencapsulation, To remove the coating solvent, warm air is passed over the coated materials as the coatings are being applied in the coating pans Medicaments are coated as spherical substrates with protective layers of various polymers. Suitable for solid particles greater than 600 microns in size for effective coating, and the process extensively employed for the preparation of controlled-release beads. 2- Air suspension techniques (Wurster) process ▪ In this process, the particulate core material, which is solid, is dispersed into the supporting air stream. ▪ The suspended particles are sprayed and coated with polymers dissolved in a volatile solvent that evaporate to leave a very thin layer of polymer on particles. ▪ This process of air-suspension is repeated several hundred times until the required coating thickness is achieved. ▪ The air stream which supports the particles also helps to dry them, and the rate of drying is directly proportional to the temperature of the air stream which can be modified to further affect the properties of the coating https://youtu.be/snLEMu1NAdM 3- Centrifugal extrusion Solution for wall coating or melt Vibration Curing nanoparticle coated with shell material Liquids are encapsulated using a rotating extrusion head containing concentric nozzles. In this process, jet of core liquid is surrounded by a sheath of wall solution or melt. As the jet moves through the air it breaks, into droplets of core, each coated with the wall solution. The droplets are in flight, the molten wall may be hardened or a solvent may be evaporated from the wall solution.  morphology of the delivery system obtained by extrusion. The advantage of extrusion is that it completely surrounds the core material with wall material (uniform coating) This process is particularly useful for heat labile substances such as flavours, vitamin-C and colours Disadvantage: Suitable only for liquids and semi-liquids core materials. 4- Solvent Evaporation/Solvent Extraction Step 1: The polymer is dissolved in a water immiscible volatile organic solvent like dichloromethane or chloroform, into which the core material is also dissolved or dispersed. Step 2: The resulting solution is added drop wise to a stirring aqueous solution having a suitable stabilizer like (polyvinyl alcohol) or Polyvinyl pyrrolidone, etc. to form small polymer droplets containing encapsulated material, thus, forming a o/w emulsion. Step 3: Removal of the organic solvent from the dispersed phase by extraction or evaporation leading to polymer precipitation and formation of the microspheres. 4- Solvent Evaporation/Solvent Extraction 4- Solvent Evaporation/Solvent Extraction Active Ingredient Polymer + Volatile organic solvent Organic Polymeric Phase Addition into an aqueous phase (+ o/w stabilizer) Formation of Oil-in-Water Emulsion Temperature increase Solvent Evaporation Particle Formation by Polymer Precipitation Recovery of Polymeric microparticles  5- Spray drying & congealing (cooling) Serves as a microencapsulation technique when an active material is dissolved or suspended; in a melt or polymer solution and becomes trapped in the dried particle. Spray drying = Aqueous Solution / Hot Air Spray congealing = Hot Melt / Cold Air Both involve:1) dispersing the core material in a liquefied coating substance 2) spraying or introducing the core - coating (and formation) of the coating is affected. mixture into some environmental condition, for a rapid solidification. Advantages The ability to handle heat- labile materials because of the short contact time in the dryer. Economic. In modern spray dryers the viscosity of the solutions to be sprayed can be as high as 300mPa. (suitable for viscous solutions) Spray drying= solidification of the coat is achieved by rapid evaporation of solvent in which coating material is dissolved Spray congealing = solidification of the coat is achieved by thermal congeal of the molten coating material. N.B: spray cooling is suitable of encapsulation of lipophilic compounds APPLICATIONS OF MICROENCAPSULATION TECHNIQUES:  Chemical methods for microencapsulation Poly-condensation Interfacial Polymerization Interfacial Cross- Linking In-situ polymerization Matrix polymerization  1- Interfacial Polymerization It is interfacial poly-condensation (polymerization) where two reactants meet at an interface and react rapidly. Used to produce synthetic fibres such as polyester, nylon and polyurethane. It is characterized by wall formation via the rapid polymerization of monomers at the surface of the droplets or particles of dispersed core material. Steps 1- A multifunctional monomer is dissolved in the core material, and this solution (organic phase) is dispersed in an aqueous phase. 2- Add reactant to the monomer aqueous phase, and polymerization quickly starts at the surfaces of the core droplets, forming the capsule walls.  1- Interfacial Polymerization (cont) ⚫ The concept of this method is the reaction between an acid chloride (function group) and a compound containing an active hydrogen atom, (such as an amine or alcohol, polyesters, polyurea, polyurethane) ⚫ Thin flexible walls form rapidly at the interface. ⚫ E.g microencapsulation of pesticides 2- Interfacial Cross- Linking In this method, the small bifunctional monomer containing active hydrogen atoms is replaced by a biosourced polymer, like a protein. Interfacial cross-linking is derived from interfacial poly- condensation and was developed to avoid the use of toxic diamines. ⚫ A reaction is performed at the interface, the acid chloride reacts with the functional groups of the protein, leading to the formation of a membrane. ⚫ The method is very versatile, and the properties of the microcapsules (size, porosity, degradability, mechanical resistance) can be customized or controlled. 37