Development and Optimization of Sustained-Release Matrix Tablets of Diclofenac Sodium Using Carboxymethylated Chitosan Through Systematic Application of Design of Experiments.

Abstract

Purpose: The study aimed to develop and optimize a sustained-release matrix tablet of diclofenac sodium (50 mg) using carboxymethylated chitosan (CMCS) as the matrix- forming polymer, in combination with hydroxypropyl methylcellulose (HPMC). The research investigated the impact of CMCS (50-200 mg) and HPMC (150-300 mg) composition on the critical quality attributes of the sustained-release matrix tablets.

Methods: A 2-factor mixture design investigated the impact of HPMC and CMCS proportions on critical quality attributes. Tablets (650 mg) were prepared by wet granulation and characterized for flow properties, hardness, and drug release kinetics. The in vitro drug release studies were carried out at 37 ± 0.5°C in a phosphate buffer of pH 6.8 using a USP type II dissolution apparatus operated at 50 rpm. The in vitro dissolution profile of the optimized formulation was compared with a marketed product, Reactin® SR, using ANOVA and model-independent methods (f1 and f2 values).

Results: Granule properties showed good flow characteristics with Carr's index (14.25- 18.36) and Hausner ratio (1.05-1.25). FTIR and DSC studies confirmed no drug-excipient interactions, with the drug's characteristic peaks maintained at 766 cm⁻¹, 1454 cm⁻¹, 1017 cm⁻¹, and 2915 cm⁻¹, and a melting endotherm at 54°C. The optimized formulation (F3) with 150 mg HPMC and 200 mg CMCS demonstrated 90.57% drug release in 8 hours following super case II transport (n = 1.11). The release kinetics best fitted the Korsmeyer- Peppas with the F0 model (R² = 0.9959). The response parameters hardness (4.2 ± 0.126 kg/cm²), t25 (115 ± 11.60 min), t50 (290 ± 21.42 min), and t90 (630 ± 31.51 min) were best fitted to the quartic model. The similarity factor (f2 = 67.63) and difference factor (f1 = 13.85) indicated the equivalency of the dissolution profile with that of the marketed formulation.

Conclusion: The study successfully developed a sustained-release matrix tablet of diclofenac sodium using CMCS as the primary matrix material. The optimized formulation demonstrated a dissolution profile comparable to the marketed product (>90% release in 8 hours), with f2 > 50 and f1 < 15, suggesting its potential as a generically equivalent alternative. Moreover, the findings indicate that CMCS is an effective carrier for sustainedrelease formulations and can potentially be applied to other drugs requiring controlled release.