DEVELOPMENT OF MATRIX TYPE TDD SYSTEM OF CARVEDILOL & HYDROCHLOROTHIAZIDE AND ITS PHARMACOKINETIC AND PHARMACODYNAMIC EVALUATIONS

The aim of the present study was to develop transdermal delivery system to deliver two cardiovascular drugs in combination of carvedilol and hydrochlorothiazide, as they have synergistic effect. Matrix type transdermal delivery system with both the drugs was prepared by film casting method using chitosan polymer. Fourier transform infra-red (FTIR) spectrometry, differential scanning calorimetry (DSC) were applied to investigate the physicochemical characteristics of the drugs in formulation. Characterization studies indicate that there were no changes in the physical state of the drug between either the drugs or polymer in the formulation. The permeations of drugs were analyzed in vitro and in vivo. The results revealed that the transdermal film released the drugs at a controlled rate for prolonged period of time 72 h and in vivo release study also showed prolonged therapeutic concentration of carvedilol and hydrochlorothiazide available in the plasma as compared to the 2 days of oral dosage form. The formulations were subjected to stability studies at 40ºC/ 75% RH and 25ºC/ 60%RH as per the ICH guidelines and it was found to be stable at all temperature conditions. Pharmacodynamic studies were performed in rats against fructose-induced hypertension and 0.9% normal saline-induced diuretics. In vivo pharmacodynamic data shows that similarity in therapeutic efficacy compared to multiple dose oral suspension.