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
T. Hamaguchi et al., 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, Chemical and Pharmaceutical Bulletin, 43(7), 1995, pp. 1204-1211
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.