PHYSICOCHEMICAL CHARACTERIZATION AND EVALUATION OF TELMISARTAN: HYDROXYPROPYL-β-CYCLODEXTRIN: TWEEN 80 INCLUSION COMPLEX

Abstract

Objective: The present work was aimed to study the effect of the ternary component on complexation efficiency of cyclodextrins towards telmisartan which is a poorly soluble anti-hypertensive agent.Methods: The elucidation of inclusion complexation of telmisartan (TEL) with hydroxypropyl-β-cyclodextrin (HP-β-CD) in the presence and absence of tween 80 was done by investigating their interactions in solid and solution state. The solid state characterization was performed using differential scanning calorimetry (DSC), powder X-ray diffraction studies (PXRD) fourier transform infra-red spectroscopy (FTIR) studies. The host guest stoichiometry was confirmed in solution state by proton nuclear magnetic resonance (1HNMR) and solution calorimetry studies. The improvement in solubility was evaluated through dissolution studies, which was further confirmed by in vivo studies.Results: In solution state, the phase solubility studies indicated 1:1 stoichiometry between TEL and HP-β-CD both in presence and absence of tween 80. The NMR and molecular modelling studies indicated the insertion of N-methyl benzimidazole and biphenyl carboxylate regions of TEL into HP-β-CD cavity suggesting the coexistence of two 1:1 complexes in equilibrium with each other. The stability constants, K1 (imidazole region of TEL-CD) and K2 (biphenyl acetic acid region of TEL-CD), were enhanced in the presence of tween 80 as evident by the higher value of stability constants. Efficacy of ternary complex was established by a significant decrease in the systolic blood pressure of deoxycorticosterone acetate (DOCA) induced hypertensive rats.Conclusion: It can be concluded that solubility of TEL was increased by encapsulation with HP-β-CD. Tween 80 further increased the complexation efficiency and decreased the bulk of cyclodextrin.