Microspheres Preparation and Evaluations.pptx

Microspheres are small spherical particles with diameters from 1 to 1000 μm. In some cases, microspheres are also known as microparticles. Microspheres can be produced from several natural and synthetic polymeric materials or even from inorganic materials

1. Microspheres: Preparation and evaluations Submitted By: Prachi Pandey*, Rahul Pal Submitted To: M r. Arsh Chanana M. Pharm (Pharmaceutics), IInd Sem. Department of Pharmaceutics, NIMS Institute of Pharmacy, NIMS University, Jaipur, Rajasthan. Microparticles are particles between 0.1 and 100 μm in size. Commercially available microparticles are available in a wide variety of materials including ceramics, glass, polymers, and metals .

2. DEFINITION Microspheres are small spherical particles, with diameter 1 µm to 1000 µm. They are spherical free flowing particles consisting of proteins or synthetic polymers which are biodegradable in nature. Microspheres representation

3. Microcapsules are those in which entrapped substance is distinctly surrounded by distinct capsule wall. Micrometrics in which entrapped substance is dispersed throughout the matrix. Classification of microspheres

4. Classification Microspheres and Microcapsules Representation

5. Microsphere types Types Description Application Bio-adhesive Microsphere Prolong residence time Nasal Gentamycin Floating Microsphere Bulk density less than gastric fluid NSAIDs, Antibiotics Radioactive Microsphere Deliver high radiating dose to target site Diagnostics: Liver, spleen Polymeric Microsphere Biodegredable and non- biodegredable swells in aq media Vaccine: Hepatitis Local: Proteins Magnetic Microsphere Localize the drug to release site Chemotherapeutics agents to liver

6. Improve bioavailability. Provide constant and prolonged therapeutic effect. Provide constant drug concentration in blood. Decrease dose and toxicity. Protect the drug from enzymatic and photolytic cleavage so it is best for drug delivery of protein. Reduce the dosing frequency and thereby improve the patient compliance Advantages

7. Disadvantage The cost is more. Reproducibility is less . Process conditions like change in temperature, pH, solvent addition, and evaporation/agitation may influence the stability of core particles. Degradation of product due to heat, hydrolysis, oxidation, solar radiation or biological agents.

8. Marketed Preparation of Microspheres Marketed Formulations of Microspheres BRAND NAME COMPANY DRUG APPLICATION Protonix ® Wyeth Pharmaceutical Germany Pantaprazole Gastric Ulcer Altinac ® Janssen Cilag Pharmaceutical inc. Tritinoin Skin regeneration Lumason ® Bracco Diagnostics inc. Sulfa Hexafluoride lipid microsphere Diagnosis and Investigation

9. Single Emulsion Technique Double Emulsion Technique Solvent Evaporation Phase Separation Coacervation Technique Spray Drying and Spray Congealing Solvent Extraction Polymerization Methods of Preparation

10. single emulsion technique Polymers in Aqueous Solution Disperse in Organic Phase ( Oil/Chloroform) Stir / Sonicate Chemical crosslinking or heat denaturation Microsphere in Organic Phase Microsphere

11. Double emulsion method Polymer in aqueous solution with drug Disperse in organic phase First Emulsion (W/O) Multiple Emulsion Microsphere in solution Microsphere Homogenization or sonication Addition of Aqueous solution PVA Addition of large aqueous solution Separate , dry, wash

12. Solvent Evaporation Core Material Coating Polymer Solution Core material disperse in liquid manufacturing vehical phase Evaporation of polymer solvent Microsphere Disperse Agitate Evaporate

13. Phase separation Coacervation Technique Aquous / Organic solution in polymer Drug disperse in polymer solution Polymer rich globules Microsphere in aquous / organic phase Microsphere Add Drug Phase separation induced by different means Solidify Separate, dry, wash

14. Spray drying / Spray congealing Polymer disperse in organic phase (acetone) Drug disperse in polymer solution with high speed homogenization Atomizes in steam of hot air Formation of small droplets Microsphere Solvent Evaporation

15. Spray drying / Spray congealing Polymer disperse in organic phase (acetone) Coating Polymer Solution Core material disperse in liquid manufacturing vehical phase Evaporation of polymer solvent Microsphere Separation by cyclone separator and drying by vacuum drying

16. Solvent extraction

17. Polymerization

18. Bulk Polymerization

19. suspension Polymerization

20. Emulsion Polymerization

21. Interfacial Polymerization

22. 1) Particle size and shape : The most widely used procedures to visualize microparticles are conventional light microscopy (LM) and scanning electron microscopy (SEM). 2) Degradation behavior : The surface chemistry of the microspheres can be determined using the electron spectroscopy for chemical analysis (ESCA). Evaluation

23. 3) Angle of repose: The powder mass was allowed to flow through the funnel orifice kept vertically to a plane paper kept on the horizontal surface, giving a heap angle of powder on paper. The angle of repose was calculated by the following equation tan ϕ =h/r Where, h & r are the height band radius of the powder cone. Evaluation

24. Evaluation 4) Bulk density: Bulk density was obtained by dividing the mass of powder by the bulk volume in cm³. It was calculated by using equation; Bulk density volume = Mass of microspheres / Bulk 5) Tapped density: It is the ratio of total mass of the powder to the tapped volume of the powder. It is expressed in g/ml. Tapped Density = Mass of the microspheres (W) / Tapped Volume of the microspheres ( Vf ) Density Apparatus

25. EVALUATION 6) Drug entrapment efficiency: It is the percentage of drug that is successfully entrapped with in microspheres Drug entrapment efficiency can be calculated using following equation % Entrapment = Actual content / Theoretical content x 100

26. EVALUATION 7) Swelling Index : It is conducted in a phosphate buffer of pH 6.8. Their diameter is measured periodically by using laser particle size distribution analyzer until they were decreased by erosion and dissolution. Swelling index= (mass of swollen microspheres - mass of dry microspheres/mass of dried microspheres) 100

27. EVALUATION 8) In-Vitro methods: Release studies for different type of microspheres are carried out by using phosphate buffer pH 7.4, mostly by rotating paddle apparatus. Agitated with 100 rpm, samples were collected at specific time intervals and replaced by same amount and analyzed. Dissolution Apparatus

28. EVALUATION 9) Adhesion property: Freshly cut piece of pig intestine is used (5 cm long),clean and wash it with isotonic saline solution. Accurate weight of microspheres was placed on mucosal surface, phosphate buffer of pH 6.8 is warmed at 37 °c was peristaltically pumped at a rate of 5 ml/min over the tissue. The duration of complete washing microspheres from pig intestine was recorded.

29. Applications Ophthalmic Drug Delivery Oral drug delivery Gene delivery (RISPERDAL CONTRA risperidone) Nasal drug delivery Buccal drug delivery Gastrointestinal drug delivery Transdermal drug delivery (TDDS) Prostate Cancer Opoids craving reducer (VIVITROL naltrexone)

30. Reference https://www.amazon.com/Microspheres-Microcapsules-Biotechnology-Preparation-Applications/dp/ 9814316474 Dhadde , Gurunath S., et al. "A review on microspheres: Types, method of preparation, characterization and application."  Asian Journal of Pharmacy and Technology”  11.2 (2021): 149-155. Vasava, Drashti , Jitendra Patel, and Umesh Upadhyay. "A review article on: Microsphere."  National Journal of Pharmaceutical Sciences  2.2 (2022): 148-154.