Abstract
The stability–pH profile of the γ-aminobutyric acid prodrug, Progabide, was found to be bell shaped, with maximum stability occurring at pH 6 to 7 with a t 1/2 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, as 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 × 10−5 M for Progabide and 33.4 × 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.
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Farraj, N.F., Davis, S.S., Parr, G.D. et al. The Stability and Solubility of Progabide and Its Related Metabolic Derivatives. Pharm Res 5, 226–231 (1988). https://doi.org/10.1023/A:1015941729400
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DOI: https://doi.org/10.1023/A:1015941729400