The effect of mechanical grinding on the formation, crystalline changes and dissolution behaviour of the inclusion complex of telmisartan and β-cyclodextrins

Telmisartan (TEL) was entrapped into beta-cyclodextrin aiming the improvement of its biopharmaceutical properties of low solubility. A solid state grinding process was used to prepare the molecular inclusion complex (MIC) for up to 30 min. The inclusion ratio of drug and P-cyclodextrin was established as 1:2 and 1:3 (mol/mol) by phase solubility study and Job Plot. DSC, XRPD and FTIR confirmed the molecular interactions between TEL and beta-cyclodextrin. Computer molecular modeling supports the presence of hydrogen bonds between guest and host and demonstrated the most probable complexes configuration. MIC_1 :2_30 and MIC_1 :3_30 enhanced the dissolution rate of the drug achieving a delivery rate comparable with the reference medicine available in the market (81% and 87% in 5 min, for MIC_1 :3_30 and Micardis (R)), respectively). These formulations showed rapid and effective antihypertensive effect against angiotensin II in rats up to 180 min, with statistically significant results against placebo and control in the first 30 min after administration. (C) 2015 Elsevier Ltd. All rights reserved.