FACTORS AFFECTING THE DISSOLUTION RATE OF SULPIRIDE FROM TABLETS COATED WITH POLYVINYLACETAL DIETHYLAMINOACETATE, A GASTRIC-FLUID-SOLUBLE POLYMER .2. EFFECT OF MECHANICAL DESTRUCTIVE FORCE AND FILM COATING STRENGTH IN THE GASTROINTESTINAL-TRACT

The bioavailability of sulpiride (SP) from a tablet coated with AEA(R) (polyvinylacetal diethylaminoacetate), a gastric-fluid-soluble polyme r, is very poor in low gastric acidity subjects in the fasting state b ut improves after food intake. To analyze factors affecting SP bioavai lability from AEA(R) film-coated tablets (AEA(R) tablets), we prepared AEA(R) cast film and AEA(R) tablets and determined the effects of mec hanical destructive force and film coating strength in the gastrointes tinal (GI) tract on SP dissolution from the tablets. With the paddle m ethod, 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 increas e in the mechanical destructive force and a change in film coating str ength. Microscopic observation of AEA(R) film coating at pH 5.0 suppor ted the marked decrease in the cast film strength observed in pH 5.0 m edium with an increase in film swelling. Thus, one important factor af fecting AEA(R) film coating strength is its swelling rate. After food intake, SP bioavailability from AEA(R) tablet improves, probably due t o increased mechanical destructive force with GI motility and decrease d film coating strength in GI fluids with increased film swelling in t he pH environment after the meal (pH 5.85). This increased SP dissolut ion rate from AEA(R) tablet leads to enhanced absorption. We concluded that the increase in mechanical destructive force acting on the table t after food intake is one of the powerful factors leading to improved drug bioavailability.