RELEASE CHARACTERISTICS OF DICLOFENAC SODIUM FROM ENCAPSULATED NATURAL GUM MINI-MATRIX FORMULATIONS

In attempts to design an oral sustained release multiple-unit dosage f orm for diclofenac sodium (D), we evaluated the use of four natural hy drophilic gums as mini-matrix formulations enclosed in a hard gelatin capsule. Carrageenan (C), locust bean (LB), karaya (K) and xanthan gum s (X) were used to produce mini-matrices (3, 4.5 and 5.5 mm in diamete r) containing a gum and D, and also with other release-regulating exci pients in different proportions, namely lactose (L), Encompress(R) (E) , cellulose acetate phthalate (CAP) and Veegum F(R) (V). The release p rofiles from several encapsulated mini-matrices in buffered dissolutio n 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 releas e exponents (It 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 wi th progressive increase in gum content but without changing the releas e behaviour. Maximum release from individual mini-matrices was > 90% a nd approaching zero-order release kinetics (n --> 1). This was due to the larger surface area to volume ratio which provided an optimum bala nce between the diffusion and dissolution mechanisms. Solubility diffe rences between the excipients did not affect the release rate, but inc reasing proportions of each excipient produced a faster release rate w ith 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.