Farraj N F, Davis S S, Parr G D, Stevens H N
Department of Pharmacy, University of Nottingham, United Kingdom.
Pharm Res. 1988 Apr;5(4):226-31. doi: 10.1023/a:1015941729400.
The stability-pH profile of the gamma-aminobutyric acid prodrug. Progabide, was found to be bell shaped, with maximum stability occurring at pH 6 to 7 with a t1/2 of 126 min. Of its metabolic derivatives, the deamidated product PGA degraded in a similar fashion to Progabide, whereas the hydrolytic degradation product SL79.182 was, a expected, a stable compound. Progabide behaved as a typical weak base, with its solubility increasing with a decrease in pH. SL79.182 behaved as a typical phenolic weak acid, with its solubility increasing with an increase in pH. Both compounds displayed low intrinsic solubilities of 14.5 x 10(-5) M for Progabide and 33.4 x 10(-6) M for SL79.182. An increase in temperature resulted in an increase in the solubility but a decrease in the stability of Progabide. The data obtained indicate that the gastric pH and gastric emptying rate will have a profound effect on the oral bioavailability of Progabide.
