Ehab M Elzayat1, Ali A Abdel-Rahman2, Sayed M Ahmed2, Fars K Alanazi1, Walid A Habib1, Adel Sakr3. 1. a Kayyali Research Chair for Pharmaceutical Industries, Department of Pharmaceutics , King Saud University , Riyadh , Saudi Arabia. 2. b Department of Industrial Pharmacy, College of Pharmacy , Assiut University , Assiut , Egypt. 3. c Department of Pharmaceutics , Future University , Cairo , Egypt.
Abstract
CONTEXT: Multiple response optimization is an efficient technique to develop sustained release formulation while decreasing the number of experiments based on trial and error approach. OBJECTIVE: Diclofenac matrix tablets were optimized to achieve a release profile conforming to USP monograph, matching Voltaren®SR and withstand formulation variables. The percent of drug released at predetermined multiple time points were the response variables in the design. Statistical models were obtained with relative contour diagrams being overlaid to predict process and formulation parameters expected to produce the target release profile. MATERIALS AND METHODS: Tablets were prepared by wet granulation using mixture of equivalent quantities of Eudragit RL/RS at overall polymer concentration of 10-30%w/w and compressed at 5-15KN. RESULTS AND DISCUSSION: Drug release from the optimized formulation E4 (15%w/w, 15KN) was similar to Voltaren, conformed to USP monograph and found to be stable. Substituting lactose with mannitol, reversing the ratio between lactose and microcrystalline cellulose or increasing drug load showed no significant difference in drug release. Using dextromethorphan hydrobromide as a model soluble drug showed burst release due to higher solubility and formation of micro cavities. CONCLUSION: A numerical optimization technique was employed to develop a stable consistent promising formulation for sustained delivery of diclofenac.
CONTEXT: Multiple response optimization is an efficient technique to develop sustained release formulation while decreasing the number of experiments based on trial and error approach. OBJECTIVE:Diclofenac matrix tablets were optimized to achieve a release profile conforming to USP monograph, matching Voltaren®SR and withstand formulation variables. The percent of drug released at predetermined multiple time points were the response variables in the design. Statistical models were obtained with relative contour diagrams being overlaid to predict process and formulation parameters expected to produce the target release profile. MATERIALS AND METHODS: Tablets were prepared by wet granulation using mixture of equivalent quantities of Eudragit RL/RS at overall polymer concentration of 10-30%w/w and compressed at 5-15KN. RESULTS AND DISCUSSION: Drug release from the optimized formulation E4 (15%w/w, 15KN) was similar to Voltaren, conformed to USP monograph and found to be stable. Substituting lactose with mannitol, reversing the ratio between lactose and microcrystalline cellulose or increasing drug load showed no significant difference in drug release. Using dextromethorphan hydrobromide as a model soluble drug showed burst release due to higher solubility and formation of micro cavities. CONCLUSION: A numerical optimization technique was employed to develop a stable consistent promising formulation for sustained delivery of diclofenac.