Optimization of Hydrophilic Matrix Tablet Formulation of Diclofenac Sodium using a Mixture Design

Abstract

Ispaghula husk was evaluated as a hydrophilic matrixing agent for the development of modified-release tablets of diclofenac sodium. Matrix tablets containing diclofenac sodium, ispaghula husk powder, lactose, micro-crystalline cellulose or cross-linked polyvinylpyrrolidone were prepared by a non-aqueous wet granulation technique. A seven-point simplex-centroid experimental design was used to investigate the influence of formulation variables on in-vitro drug release. In-vivo efficacy was evaluated in man using a parallel design. The swollen tablets remained intact during the dissolution test. The time required for 50 or 90% drug release was dependent on the amount of husk powder and the nature of adjuvant in the matrix. The drug was released at a slower rate when the drug to husk ratio was 1:1. Relatively faster drug release was found when higher levels of lactose and microcrystalline cellulose were used. The in-vitro drug dissolution data of a selected formulated product was found to be comparable with that of commercial products. The results of the human bioavailability study confirmed modified drug release from the formulated product. Ispaghula husk powder can be used as a hydrophilic matrixing agent for the development of modified-release dosage forms. Lactose or microcrystalline cellulose are necessary for compressibility of the tablets.