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
T. Hamaguchi et al., 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, Chemical and Pharmaceutical Bulletin, 43(12), 1995, pp. 2205-2210
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.