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Transdermal Drug Delivery Systems (TDDS) exists for a long time such as creams, and ointments for topical ailments.Incorporating drugs in transdermal patch ismore recent application. Liquid reservoir system, solid reservoir/peripheral adhesive system or matrix (drug in adhesive) system may be used to deliver the drug through skin. In present work thirty six matrix type transdermal patch formulations of diclofenac sodium, diclofenac potassium, diclofenac diethylamine and flurbiprofen (nine each) were developed by using hydroxypropylmethylcellulose (HPMC 4000 cps,), polyvinylpyrolidine (PVP K-30,) and ammonio methacrylate copolymer type A (Eudragit RL-100). Different skin permeation enhancers like isopropyl myristate, isopropyl palmitate and tween 80 were incorporated in the formulations. The influence of various formulation variables, such as initial drug load and certain skin permeation enhancers on permeation characteristics of selected analgesics from the prepared formulations was studies through hairless abdominal rabbit skin by using the modified Franz diffusion cell. The permeation parameters were estimated by Chow method following the Fick’s law of diffusion. The penetration profiles of all formulations were influenced significantly (p <0.05) by the addition of enhancers in comparison to formulation controls (without enhancers) and commercially available product (market control). Among the enhancers studied, isopropyl myristate and isopropyl palmitate produced better results with high relative permeation ratio (14.61, 27.40) and enhancing factor (32, 7.83). All the formulations showed good stability and reproducibility. The prepared patch formulations resulted better permeability as compared to the controls with high apparent permeation rates (121.18 ± 34.37 µg.h-1 cm-2) and diffusion coefficients (8.68 ± 0.43 cm2/s × 10-4) with shorter lag times (1.0 ± 0.15 h). The diffusion coefficients were found independent of initial drug load for all formulations. Release profiles were evaluated by model-dependent approaches. The drug release from almost all formulations was best explained by zero order equation, as the plots showed highest linearity (r2 > 0.952), followed by Higuchi equation. The mechanism of drug release for most of formulations was super case II transport and in few, non-Fickian diffusion. The pharmacokinetic parameters of optimized formulations for each drug were determined from blood levels which revealed a profile typical of sustained release formulation having low elimination rate constants and high Mean Residence Time with the ability to maintain adequate plasma levels for 24 h i.e. up to the next application. The higher steady-state flux, diffusion coefficient and permeability coefficient, as well as the decreased lag time of permeation ofdiclofenac sodium 5% with IPP, 5% diclofenac potassium with IPM, 5% diclofenac diethylamine with IPP and flurbiprofen 10% with IPM as compared to formulation control (without enhancer) and commercially available gel (market control) was obtained. The faster permeation of the drug as compared to the controls could be attributed to the incorporation of skin penetration enhancer. The pharmacokinetic analysis confirmed that the optimized formulations exhibit typical sustained release phenomenon having low elimination rate constants and high MRT with the ability to maintain adequate plasma levels for 24 h i.e. up to the next application. Therefore it is concluded that the incorporation of skin penetration enhancers like IPM and IPP are promising in developing matrix type patch formulation.
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