Design and Evaluation of Diclofenac Sodium Megaloporous Matrix System Aimed for Colonic Drug Delivery

Abstract

Megaloporous controlled release tablets of diclofenac sodium (DS) were prepared with two kinds of granules. One of them is the restraining-phase matrix granule (RMG) and it controls the release rate of the drug. The other one is the soluble housing-phase matrix granule (HMG) and controls liquid penetration into the system. Carnauba wax and Eudragit L 100 polymers were used to constitute the restraining and housing matrix phases, respectively. The prepared tablets were evaluated for various parameters. <em>In vitro</em> drug release study was carried out in simulated gastric fluid (pH 1.2) for the first 2 h and in phosphate buffer (pH 7.2) for the next 10 h following USP 25 paddle method. Two independent model methods, AUC and Lin Ju and Liaw's difference factor (ƒ₁) and similarity factor (ƒ₂) were used to compare various dissolution profiles. The fabricated megaloporous matrix tablets released only 3 to 5% of DS in pH 1.2 depending on the proportion of carnauba wax used in the RMG. Increase in polymer content/hardness value of the tablet resulted in a significant decrease in AUC_0-2 h and AUC_2-12 h values . The <em>f</em><em>₁</em>and<em> f</em><em>₂</em>analysis also confirms the discrimination between corresponding dissolutionpairs. The dissolution profiles of an ideal matrix formulation containing 15.77% carnauba wax and 6.76% Eudragit L100 was found to be comparable with the reference product (Voveran^® SR) and theoretical release profile. The drug release from all fabricated products and reference product followed better Higuchi model than the zero order and first order kinetic models. Ritger-Peppas model analysis indicated that the DS release followed non-Fickian transport mechanism. From the above analysis, it is evident that the release mechanism of DS from matrix tablet is influenced by both hardness and polymer contents. The stability profiles indicate that the physico-chemical properties of the tablets are not affected on storage at 45°C /75% RH up to 6 months.