Factors Affecting the Dissolution Rate of Sulpiride from Tablets Coated with Polyvinylacetal Diethylaminoacetate, a Gastric-Fluid-Soluble Polymer. II. Effect of Mechanical Destructive Force and Film Coating Strength in the Gastrointestinal Tract

The bioavabilaility of sulpiride (SP) from a tablet coated with AEA[○!R] (polyvinylacetal diethylaminoacetate), a gastric-fluid-soluble polymer, is very poor in low gastric acidity subjects in the fasting state but improves after food intake. To analyze factors affecting SP bioavailability from AEA[○!R] film-coated tablets (AEA[○!R] tablets), we prepared AEA[○!R] cast film and AEA[○!R] tablets and determined the effects of mechanical destructive force and film coating strength in the gastrointestinal (GI) tract on SP dissolution from the tablets. With the paddle method, rapid SP dissolution occurred at pH 4.0 or below but not at pH 5.0 or above. Using the disintegration test method, dissolution at pH 5.0-5.8 markedly increased as the film coating broke due to an increase in the mechanical destructive force and a change in film coating strength. Microscopic observation of AEA[○!R] film coating at pH 5.0 supported the marked decrease in the cast film strength observed in pH 5.0 medium with an increase in film swelling. Thus, one important factor affecting AEA[○!R] film coating strength is its swelling rate. After food intake, SP bioavailability from AEA[○!R] tablet improves, probably due to increased mechanical destructive force with GI motility and decreased film coating strength in GI fluids with increased film swelling in the pH environment after the meal (pH 5.85). This increased SP dissolution rate from AEA[○!R] tablet leads to enhanced absorption. We concluded that the increase in mechanical destructive force acting on the tablet after food intake is one of the powerful factors leading to improved drug bioavailability.