Studies On Transdermal Drug Delivery System Of Felodipine And Metoprolol

Fixed-dose combination antihypertensive therapy has been available for many years and is being used increasingly in the management of hypertension. The inherent advantages of fixed-dose combination therapy reside in its achieving increased efficacy by using drugs that complement each other's action and using low doses to minimize adverse effects. Flodipine and metoprolol lower BP via different but complementary mechanisms, in combination they are particularly effective and has become one of the most important regiments to improve BP control. But they are subjected to extensive and highly variable hepatic first pass metabolism following oral administration, with a reported systemic bioavailability between 15%~25% for flodipine and 30%~40% for metoprolol respectively, which results in undesired compliance and BP control. Therefore, the development of transdermal flodipine and metoprolol avoiding hepatic first pass metabolism to enhance bioavailability and maintaining appropriate blood levels for a prolonged time without adverse effects associated with frequent oral administration is very important.The aim of the present study was to develop the monolithic adhesive dispersion type transdermal drug delivery system of flodipine and metoprolol with the excipient Eudragit E PO and Eudragit RL PO, to evaluate in vitro release and permeation of drugs at a controlled rate to provide a therapeutically effective drug level for a longer period of time from the transdermal patch and to evaluate pharmacokinetics and pharmacodynamics of flodipine and metoprolol from the TDDS in normotensive rabbits and spontaneously hypertension rats. This study was further amalgamated with investigation of physico-chemical characteristics, irritation to skin of the patch and preparation, in vitro drug release, mechanism of permeation and physico-chemical characteristics of flodipine solid lipid nanoparticles (SLN).The effect of different categories of penetration enhancers on the transdermal absorption of flodipine and metoprolol were investigated by in vitro permeation studies. Pretreatment of rat skin with Azone/Oleic acid/1,2-PG, Azone/Turpentine oil/1,2-PG and Azone/Eucalyptol/1,2-PG produced in all cases an increase in the flux of flodipine and metoprolol. Azone/Eucalyptol/1,2-PG showed the greatest ability to enhance the flux and the deposit effect of both flodipine and metoprolol in mouse,SD rat and rabbit skin.To develop a HPLC assay which was rapid, simple, convenient, accurate, reproducible and reliable for simultaneously determining metoprolol tartrate and...