Factors Affecting Dissolution Rate of Sulpiride from Tablets Coated with Polyvinylacetal Diethylaminoacetate, a Gastric-Fluid-Soluble Polymer. I. Effect of Ionic Strength of Gastrointestinal Fluids

• Published in: Chemical & pharmaceutical bulletin Vol. 43; no. 7; pp. 1204 - 1211
• Main Authors: YAMANAKA, You, MIZUNO, Nobuyasu, TAMURA, Shigeki, HAMAGUCHI, Tsuneo, MIYAKE, Masatoshi, SHINKUMA, Denji
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 15.07.1995; 公益社団法人日本薬学会; Maruzen; Japan Science and Technology Agency
• Subjects: AEA [○!R]; Biological and medical sciences; dissociation; dissolution rate; film-coated tablet; General pharmacology; ionic strength; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; sulpiride; Phosphates; Stomach; Pharmaceutical technology; Control release polymer; Psychotropic; Bile salt; Acetate; Bioavailability; Buffer solution; Dissolution; In vitro; Vinyl acetate polymer; Medium effect; Ionic strength; Antisecretory agent; Dosage form; pH; Active ingredient; Kinetics; Aqueous solution; Coated tablet; Release; Physicochemical properties
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.43.1204

The bioavailability of sulpiride (SP) from a tablet coated with AEA [○!R] (polyvinylacetal diethylaminoacetate), used as a gastric-fluid-soluble polymer, is very poor in low gastric acidity subjects in the fasting state but improves after food intake. To analyze the factors affecting 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 from 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 below 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 (μ) of the medium rose, reaching maximum at μ=0.3. Microscopic observations and measurements of film coating thickness revealed that the increased dissolution rate of SP from the tablet with higher ionic strength (μ=0.3) was due to promotion of the dissolution of the AEA [○!R] film coating. Data from pH titration showed that increased ionic strength (μ=0.3) resulted in higher apparent dissociation, which increased the solubility of AEA [○!R] in the medium. We concluded that the ionic strength in GI fluids is one of the factors affecting the bioavailability from AEA [○!R] tablet. After food intake, the bioavailability of SP from the tablet improves, probably due to increased apparent dissociation of AEA [○!R] caused by an increase in ionic strength from the meal (ca. μ=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 enhanced absorption.