title: 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 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.
authors.affiliation: Faculté de Pharmacie, Université de Montréal, Québec, Montreal, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Rahmouni
authors.forename: F
authors.initials: F
authors.lastname: Chouinard
authors.forename: F
authors.initials: F
authors.lastname: Nekka
authors.forename: V
authors.initials: V
authors.lastname: Lenaerts
authors.forename: J C
authors.initials: JC
authors.lastname: Leroux
mesh_terms: D000688:Amylose / Q000737:chemistry / Q000378:metabolism*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000737:chemistry*; D004795:Enzyme Stability; D005744:Gastric Acid / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008954:Models, Biological; D009994:Osmolar Concentration; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011312:Pressure; D013607:Tablets / Q000737:chemistry; D013995:Time; D000516:alpha-Amylases / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D013607:Tablets; D004008:Diclofenac; D065347:Hypromellose Derivatives; D011142:Polyvinyl Alcohol; D008747:Methylcellulose; D000688:Amylose; D000516:alpha-Amylases