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A Crosslinked Calcium-Alginate-Pectinate-Cellulose Acetophthalate Gelisphere System for Linear Drug Release

This study proposes a novel binary crosslinked ternary multiple-unit system, collectively referred to as calcium-alginate-pectinate-cellulose acetophthalate gelispheres (CAPCA), for the purpose of obtaining linear, controlled drug release. This polymeric system, composed of sodium alginate, pectin, and cellulose acetophthalate, was developed through a binary crosslinking reaction in a composite aqueous system consisting of calcium and acetate ions. The crosslinking reaction was optimized in terms of maximizing drug release suppression and could be obtained by exposing the gelispheres for 24 hours to a combined aqueous solution of 15% w/v acetic acid and 2% w/v calcium chloride. The highly acidic nature of this solution (pH 1.9) was desirable for enhancing the drug entrapment efficiency of the gelispheres. Synchronization of matrix swelling and erosion appeared to be responsible for the attainment of zero-order drug release. However, such perfect synchronization was only achievable through application of the ternary polymeric combination presented in this work. The main advantages of the ternary system shown in this study over the previously presented binary calcium-alginate-pectinate system (CAP) proposed by Pillay and Fassihi (1999a, 1999b), was provision of extended drug release over 18 hours, minimization of late-phase drug release tapering, and provision of superior linearity in drug release profiles. Kinetic modeling of dissolution data using various power law equations highlighted the significance of matrix relaxation and erosion in modulation of drug release rate. In all cases of model fitting excellent correlation (r 2 > 0.98) was obtained between observed and predicted data. Textural profiling of crosslinked gelispheres reflected a significantly lower reduction in matrix resilience as the concentration of cellulose acetophthalate was increased in the gelisphere formulation. This may be attributed to the concentration-dependent matrix plastic-transforming property of cellulose acetophthalate.