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Mamatha Tirunagari,Mukkanti Khagga,Ramesh Gannu,Venkateswara Rao Jangala 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.7
Isradipine (ISDP) is an effective calcium channel blocker used in the treatment of hypertension. It undergoes extensive first pass metabolism and bioavailability through the oral route is only about 15 to 24%. Hence we attempted to develop a matrix type controlled transdermal drug delivery system for ISDP. Formulations A1, A2, A3 were composed of Eudragit RL100 and hydroxypropyl methyl cellulose (HPMC) in 1:3, 1:1, 3:1 ratios; A4, A5, A6 were composed of Eudragit RS100 and HPMC in 1:3, 1:1, 3:1 ratios. All six formulations carried 5 mg of ISDP/patch area, 5% v/w of D-limonene, 15 % v/w of propylene glycol in methanol:dichloromethane (1:1). The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy and differential scanning calorimetry. The results suggested no physicochemical incompatibility between the drug and the polymers. The prepared transdermal drug delivery system were evaluated for physicochemical characteristics, mainly in vitro release and ex vivo permeation. The ex vivo permeation studies were carried out across excised rat skin using Franz diffusion cell. All the formulations exhibited satisfactory physicochemical characteristics. Cumulative amount of the drug released in 36 h from the six formulations were 1695.32, 1527.89, 1455.54, 1485.65, 1282.81 and 916.88 μg/cm2 respectively. Corresponding values for the cumulative amounts of drug permeated across the rat skin for the above matrix films were 1456.29, 1284.70, 1182.99, 1212.72, 1046.05, and 782.60 μg/cm2 respectively. By fitting the data into zero order, first order and Higuchi models, it was concluded that drug release from matrix films followed Higuchi model and the mechanism of drug release was diffusion mediated. Based on the physical evaluation, in vitro drug release and ex vivo permeation characteristics, it was concluded that for potential therapeutic use, monolithic drug matrix films A1, may be suitable for the development of a transdermal drug delivery system of ISDP.
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