Enzymatic degradation of cross-linked high amylose starch tablets and its effect on in vitro release of sodium diclofenac

Abstract

The influence of several physicochemical parameters on enzymatic hydrolysis and the in vitro release of sodium diclofenac (SDic) from cross-linked high amylose starch (Contramid) (CLA) tablets was evaluated. These parameters included pH, ionic strength of the medium, enzyme concentration, compression force and incorporation of gel-forming polymers such as hydroxypropyl methylcellulose (HPMC), poly(ethylene oxide) (PEO) and poly(vinyl alcohol) into the tablet. Pure CLA tablets were incubated in phosphate buffer (pH 6.8) containing α-amylase and the extent of enzymatic erosion was determined by gravimetry. Release of SDic from CLA tablets, in the presence of α-amylase, was measured using a USP type III dissolution apparatus. For low α-amylase concentrations (<2250 IU/l), the drug release was mainly diffusion-controlled. At higher α-amylase concentrations (>4500 IU/l) both diffusion and erosion contributed to the release of SDic. The hydrolysis kinetics of CLA tablets by α-amylase was biphasic. During the first phase (2–4 h), the hydrolysis rate was hyperbolically related to the α-amylase concentration but was practically α-amylase concentration-independent during the second phase. Enzymatic erosion and drug release kinetics appear to be relatively independent of ionic strength, pre-incubation time in simulated gastric fluid, and compression force of the tablets (6–34 kN). Incorporation of HPMC or PEO into the tablet resulted in a significant decrease of both tablet erosion and drug release rates.