Release characteristics of diclofenac sodium from encapsulated natural gum mini-matrix formulations

Abstract

In attempts to design an oral sustained release multiple-unit dosage form for diclofenac sodium (D), we evaluated the use of four natural hydrophilic gums as mini-matrix formulations enclosed in a hard gelatin capsule. Carrageenan (C), locust bean (LB), karaya (K) and xanthan gums (X) were used to produce mini-matrices (3, 4.5 and 5.5 mm in diameter) containing a gum and D, and also with other release-regulating excipients in different proportions, namely lactose (L), Encompress® (E), cellulose acetate phthalate (CAP) and Veegum F® (V). The release profiles from several encapsulated mini-matrices in buffered dissolution medium (pH 7.0) showed that sustained release of D up to 77% of drug content was achieved from mini-matrices containing LB, X and K, while C did not produce sufficient sustained release. The calculated release exponents (n values) indicated that release behaviour was anomalous (non-Fickian). Polymer swelling and relaxation were both involved in the release process. For X, the drug release rate declined linearly with progressive increase in gum content but without changing the release behaviour. Maximum release from individual mini-matrices was > 90% and approaching zero-order release kinetics ( n → 1). This was due to the larger surface area to volume ratio which provided an optimum balance between the diffusion and dissolution mechanisms. Solubility differences between the excipients did not affect the release rate, but increasing proportions of each excipient produced a faster release rate with the release mechanism changing from anomalous to Case II and then to Super Case II transport. The amount of gum present appeared to play the dominant role in determining the drug release rate.