Enhanced gastric stability of esomeprazole by molecular interaction and modulation of microenvironmental pH with alkalizers in solid dispersion

In this study, we prepared new gastric fluid resistant solid dispersions (SDs) containing alkalizers. Then, new mechanistic evidence regarding the effects of pharmaceutical alkalizers on the aqueous stability of EPM in simulated gastric fluid was investigated. The alkalizer-loaded SD were prepared by dissolving or dispersing EPM, hydroxypropyl methylcellulose (HPMC) 6 cps, and an alkalizer, in ethanol 50% (v/v) followed by spray drying. Nine different alkalizers were assessed for in vitro stability in two media, simulated gastric fluid (pH 1.2 buffer) and simulated intestinal fluid (pH 6.8 buffer). The microenvironmental pH (pHM) was measured to evaluate the effect of the alkalizer on the pHM of SDs. Drug crystallinity and morphology of the SDs were also examined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The interactions among EPM, the polymer, and the alkalizer were elucidated by Fourier transform infrared (FTIR) spectroscopy. The in vivo absorption studies of the optimized alkalizer-containing SD and the enteric-coated reference tablet Nexium® were then conducted in beagle dogs. Among alkalizers, MgO loaded in SDs proved to be the best alkalizer to stabilize EPM in simulated gastric fluid. pHM values of the alkalizer-containing SDs were significantly higher than that of the SD without alkalizer. The pHM values decreased in the following order: MgO, Na2CO3, Ca(OH)2, and no alkalizer. DSC and PXRD dat...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research