Development and optimization of pluronic® F127 and HPMC based thermosensitive gel for the skin delivery of metoprolol succinate

The aim of the present investigation was to prepare and optimize suitable combination of polymers hydroxypropyl methylcellulose (HPMC) and pluronic (R) F127 (PN F127) for the development of thermosensitive gel of Metoprolol succinate (MS) using central composite design (CCD). The effect of formulation factors (concentration of HPMC and PN F127) on responses such as cumulative percentage release (CPR) of MS, bioadhesive force (BF) and viscosity was measured statistically. Quadratic model was found to be best fit model among different models used in the study. The optimum conditions were found to be 0.92% of HPMC and 15% of PN F127. Under these conditions, the predicted CPR, BF and viscosity were found to be 84.94 mu g/cm(2), 41.56 gf and 48.94 Pa s, respectively. Ex vivo permeation of MS from optimized thermosensitive gel across abdominal skin of rat demonstrated highest flux (64.35 mu g/cm(2)/h) for the gel formulation containing 1,8-cineole (5% w/w). The hypotensive activity was performed on normotensive rabbits and the results showed that the optimized formulation prolonged the activity up to 12 h. The above findings indicated that thermosensitive gel of MS for skin application exhibited strong potential against hypertension and expected to provide a better alternative to oral MS formulations. (C) 2016 Elsevier B.V. All rights reserved.