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  • Title: Enzymatic degradation of cross-linked high amylose starch tablets and its effect on in vitro release of sodium diclofenac.
    Author: Rahmouni M, Chouinard F, Nekka F, Lenaerts V, Leroux JC.
    Journal: Eur J Pharm Biopharm; 2001 May; 51(3):191-8. PubMed ID: 11343882.
    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 alpha-amylase and the extent of enzymatic erosion was determined by gravimetry. Release of SDic from CLA tablets, in the presence of alpha-amylase, was measured using a USP type III dissolution apparatus. For low alpha-amylase concentrations (<2250 IU/l), the drug release was mainly diffusion-controlled. At higher alpha-amylase concentrations (>4500 IU/l) both diffusion and erosion contributed to the release of SDic. The hydrolysis kinetics of CLA tablets by alpha-amylase was biphasic. During the first phase (2-4 h), the hydrolysis rate was hyperbolically related to the alpha-amylase concentration but was practically alpha-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.
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