Improved pH-dependent drug release and oral exposure of telmisartan, a poorly soluble drug through the formation of drug-aminoclay complex.

Abstract

Telmisartan (TEL) belongs to BCS class II (low solubility/high permeability) and exhibits the pH-dependent drug release. Since 3-aminopropyl functionalized magnesium phyllosilicate (aminoclay) can intercalate or adsorb the negatively charged molecules via the electrostatic interaction, TEL-aminoclay complex was synthesized to improve the pH dependent drug release and the oral exposure of TEL. Co-precipitation method was adopted to incorporate TEL into aminoclay with the variation of drug/aminoclay ratios, and then dissolution profiles of TEL from TEL-aminoclay complex were evaluated at different pHs. Structural characterization was performed by XRD, ATR-FTIR, and TEM, indicating the electrostatic interaction between TEL and the surface of the aminoclay lamellae. Furthermore, drug crystallinity was changed to an amorphous form via the molecular interactions between TEL and aminoclay. TEL exhibited rapid and complete dissolution at pH 1.2 within 15 min from all the tested formulations. However, while the untreated powder indicated negligible dissolution at pH 4 and pH 6.8, the formation of drug-clay complex significantly improved the dissolution rate as well as the extent of drug release at the higher pHs. In addition, following an oral administration of TEL-aminoclay, Cmax and AUC of TEL increased by about 8 and 5 fold respectively, while Tmax was shorten. The results suggest that formation of aminoclay complex should be promising to enhance the bioavailability of a poorly soluble drug, TEL.