PHARMACEUTICAL COMPOSITION OF CANDESARTAN CILEXETIL WITH P-GLYCOPROTEIN INHIBIOTR amp; PROCESS FOR PREPARATION THEREOF

摘要

The invention relates to develop suitable; pharmaceutical compositions/formulations of Candesartan cilexetil (CAN) having increased bioavailability of the drug and without any toxicity or any side effects. It specifically relates to pharmaceutical compositions/formulations of Candesartan cilexetil and Pgp (P Glycoprotein) having increased bioavailability of Candesartan (CDS) and without any toxicity or any side effects for effective treatment of hypertension or heart failure in clinical therapeutics. More specifically it relates to tablet formulations of freeze-dried candesartan cilexetil loaded solid dispersions in excipient and naringin achieving enhanced bioavailability and without any toxicity or any side effects for effective treatment of hypertension or heart failure in clinical therapeutics. It also relates to the process for preparation of pharmaceutical compositions/formulations of freeze-dried candesartan cilexetil loaded solid dispersions in excipient and naringin (or its active metabolite naringenin). having increased bioavailability and without any toxicity or any side effects for effective treatment of hypertension or heart failure, in clinical therapeutics. The invention demonstrates the effects of P-gp inhibitors for the permeability of poorly water-soluble drugs from their solid dispersions using hydrophilic polymer in the presence of P-gp inhibitors as a novel concept of employing naturally occurring bio-flavonoid as pharmaceutical adjuvant with absorption-improving potential as P-gp efflux inhibitors after significant improvement of aqueous solubility of poorly water-soluble drugs as amorphous forms. The results demonstrated that the intestine plays an important role in the net absorption and disposition of CAN, which showed that naringin increased significantly the oral bioavailability of candesartan, suggesting the involvement of P-glycoprotein in CAN disposition. It also revealed that naringin, a P-glycoprotein inhibitor can be used a pharmaceutical excipient for developing oral dosage forms to increase intestinal permeability and in-vivo pharmacokinetic performance of candesartan cilexetil to enhance oral bioavailability.