Microenvironmental pH modifying films for buccal delivery of saquinavir: effects of organic acids on pH and drug release in vitro

Buccal delivery of saquinavir has the advantage to bypass the gastrointestinal enzymatic degradation and the hepatic first-pass metabolism. Saquinavir has a pH-dependent solubility and is poorly soluble in human saliva at the physiological pH. Decreasing microenvironmental pH (pH _M) in saliva may increase saquinavir release from buccal formulations. The present study aimed to investigate the effects of organic acids on the pH _M, saquinavir release in vitro and the solid-state form of saquinavir. An UV/Vis imaging method was used to measure pH _M. After 5 min of swelling of the buccal films containing malic acid, pH _M was reduced from 6.8 to 5.4. The films containing malic acid were more efficient in maintaining low pH _M than films containing citric acid and succinic acid. Addition of organic acids in the buccal films resulted in a faster drug release than films without acids due to the reduced pH _M. However, the enhancement of saquinavir release was limited by the fast release of organic acids. Addition of malic acid and citric acid suppressed the crystallization of saquinavir during 3 months storage at the elevated temperature (40 °C) and humidity (RH 75%) respectively. These results suggest that pH _M modifying film is a potential formulation strategy for buccal delivery of saquinavir.