1. DEVELOPMENT, OPTIMIZATION AND PROCESS VALIDATION OF THE MODIFIED QUASSI EMULSION SOLVENT DIFFUSION METHOD FOR THE PREPARATION OF MICROSPONGES Rishabh Srivastava*, Kamla Pathak Department of Pharmaceutics, Rajiv Academy for Pharmacy, Mathura, Uttar Pradesh- 281001

2. Introduction Microsponges are porous microspheres having numerous interconnected voids in the particle, loaded with an active ingredient within a collapsible structure along with the large porous surface. These microparticles have characteristic feature in the form of their capacity to ‘adsorb on its surface’ and/or ‘load into the bulk’ of the particle, the high quantity of active pharmaceutical ingredients. In spite of using conventional technique to prepare microsponges we had developed the method to prepare microsponges using porogen incorporation technique and used sodium chloride as porogen.

3. OBJECTIVE The objective of this study is to develop, optimize and validate a novel technique for preparation of microsponges by incorporating a porogen to modify the quassi emulsion solvent diffusion method.

4. Outline for the developed technique organic solution of the polymer aqueous solution of the porogen 2% v/v Span 80 vigorous stirring internal aqueous phase porogen 1% w/w equivalent to the polymer emulsified properly to form a w/o emulsion The prepared w/o emulsion is redispersed in 1% w/v PVA solution to form w/o/w emulsion and stirred continuously, filtered, dried and kept in dessicator

5. Optimization of the process variables Parameters optimized PVA concentration Volume of the external phase Porogen content Concentration of internal phase stabilizing agent Temperature Stirring time These have been optimized for particle shape, aggregation and for better cross-linking of microparticles

6. Process variablesLevelsRemarks PVA concentration (% w/v) 12Higher concentration lead to the formation of flakes in spite of spheres Stablizing agent (%) 12Low content lead to the phase separation in internal w/o emulsion Volume of external phase (ml) 50100Low volume lead to the aggregation of the microparticles Porogen content (% w/w) 13Higher content lead to the formation of irregular structure Temperature (°C)2030Higher temperature lead to the rapid crosslinking and formation of irregular particles Stirring time (hr)824Higher stirring time lead to the better crosslinking

7. Fig. 1: Photomicrograph of the prepared microsponges showing spherical shape Fig. 2: SEM of the prepared microsponges showing porous surface

8. Validation The developed technology has been validated for the reproducibility in the result. It has been done by repeating the developed methodology for various times.

9. Result Various process variables had been optimized for the developed technique. Porogen content of 1% w/w provided no disruption to the shape. Span 80 was selected as stabilizing agent for internal w/o emulsion. It can stabilize the internal phase when used in the concentration of 2% v/v. A concentration of 1% w/v of PVA gives spherical particles. Low temperature was required for better cross-linking. While a stirring time of 24 hrs and high volume of external continuous phase provided better deaggregation of the particles.

10. Conclusion An optimized and validated novel technique for the preparation of the microsponges has been developed. These microsponges can be used as the drug carriers for the rate modulated drug delivery of a poorly water soluble drug.

11. Presented at 26 th ANNUAL CONFERENCE OF INDIAN PHARMACY GRADUATES ASSOCIATION PHARMACEUTICAL OPPORTUNITIES AND CHALLENGES OF THE NEW DECADE 2 nd APRIL 2011 NEW DELHI