The aim of this study is to investigate the effect of the pharmaceutical alkalizers on the stability of EPM which is an proton-pump inhibitor (PPI) drug in gastro-intestinal fluid. The alkalizer-added solid dispersion containing EPM were prepared by dissolving (or dispersing) EPM, alkalizer, and Opadry®, in ethanol 50% followed by spray drying. Nine different alkalizers were tested for the stability enhancement of EPM assessed by in vitro stability testing in two media, gastric fluid (pH 1.2 buffer), and intestinal fluid (pH 6.8 buffer). The microenvironmental pH (pHM) was measured to elucidate the effect of alkalizer on pHM of solid dispersions. Drug crystallinity and morphology of pure drug and drug-loaded solid dispersion were examined by DSC, PXRD, and SEM. The interaction among the drug, carrier and alkalizer were clarified by FT-IR spectra. Alkalizer A8 was proved to be the best alkalizer to stabilize EPM in both gastric and intestinal fluids when incorporated in solid dispersion containing EPM. pHM of EPM alkalizer-containing solid dispersion were remarkably higher than that of non-alkalizer counterpart. The pHM value was in the decreasing order: A8, A1, A2, and no alkalizer. The DSC, PXRD data exhibited a change in EPM crystallinity in solid dispersion from crystalline to amorphous. FT-IR indicated a strong molecular interaction between EPM, alkalizer and Opadry®, especially A8 showed the strongest interaction with EPM. SEM data showed a relatively spherical shape of A8-incorporated solid dispersion compared to the obscure shape of pure drug. This study provides a promising approach for stabilization of acid-labile drug, thereby improving drug bioavailability.
Key words: alkalizer, solid dispersion, microenvironmental pH (pHM), acid-labile drug, drug stability.
