FACTORS AFFECTING DISSOLUTION RATE OF SULPIRIDE FROM TABLETS COATED WITH POLYVINYLACETAL DIETHYLAMINOACETATE, A GASTRIC-FLUID-SOLUBLE POLYMER .1. EFFECT OF IONIC-STRENGTH OF GASTROINTESTINAL FLUIDS

The bioavailability of sulpiride (SP) from a tablet coated with AEA(R) (polyvinylacetal diethylaminoacetate), used as a gastric-fluid-solubl e polymer, is very poor in low gastric acidity subjects in the fasting state but improves after food intake, To analyze the factors affectin g SP bioavailability from an AEA(R) film-coated tablet (AEA(R) tablet) , we prepared AEA(R) cast film and AEA(R) tablets and investigated the physicochemical properties of gastrointestinal (GI) fluids affecting the dissolution of the film coating and the dissolution rate of SP fro m the tablets, The dissolution time of AEA(R) cast film was shortened with an increase in the ionic strength of the medium, but was delayed by an increase in viscosity and addition of sodium taurocholate to the medium, The AEA(R) tablet showed rapid dissolution of SP at pH 4 or b elow but not when the pH was 5.0 or above, in pH 5.0-5.8 media, the SP dissolution rate from the tablet increased as the ionic strength (mu) of the medium rose, reaching maximum at mu=0.3, Microscopic observati ons and measurements of film coating thickness revealed that the incre ased dissolution rate of SP from the tablet with higher ionic strength (mu=0.3) was due to promotion of the dissolution of the AEA(R) film c oating, Data from pH titration showed that increased ionic strength (m u=0.3) resulted in higher apparent dissociation, ,which increased the solubility of AEA(R) in the medium, We concluded that the ionic streng th in GI fluids is one of the factors affecting the bioavailability fr om AEA(R) tablet. After food intake, the bioavailability of SP from th e tablet improves, probably due to increased apparent dissociation of AEA(R) caused by an increase in ionic strength from the meal (ca. mu=0 .3). This increases the dissolution rate of the film coating and thus, the dissolution rate of SP from the AEA(R) tablet, leading to enhance d absorption.