A NOVEL APPROACH TO INCREASE THE BIOAVAILABILITY OF CANDESARTAN CILEXETIL BY PRONIOSOMAL GEL FORMULATION: IN-VITRO AND IN-VIVO EVALUATION
Objective: The oral bioavailability of Candesartan cilexetil is less (<15%), so in this study an approach has been made to increase its bioavailability by proniosomal gel formulation.
Methods: The proniosomal formulation of Candesartan cilexetil was prepared by slurry method, using span 60 and Tween 60 as non-ionic surfactants, maltodextrin as carrier and cholesterol and soya lecithin as stabilizers. Prepared gel formulations were evaluated for compatibility study, entrapment efficiency, vesicle size, surface morphology, in-vitro diffusion studies, in-vitro skin permeation studies, in-vivo pharmacokinetics studies, various release kinetic studies and stability studies.
Results: FT-IR study showed no interaction between drugs and other excipients, drugs and excipients are compatible. Mean vesicles size of proniosome derived niosome was found in the range of 16.34 Âµm-32.48 Âµm and 7.25-16.45 Âµm before and after shaking. An optimized formulation A3 containing a 2:1 ratio of span 60 and cholesterol showed maximum entrapment (86.17%) and in-vitro drug release (93.8%) compared to other formulations. In-vitro skin permeation studies were carried out using Albino rat skin and results showed that formulation A3 exhibited 88.65% drug permeation in a steady-state manner over a period of 24 h with a flux value of 1.94 Âµg/cm2/h and enhancement ratio of 3.73. In-vivo pharmacokinetics studies of proniosomal gel formulation A3 showed a significant increase in bioavailability (1.425 folds) compared with an oral formulation of Candesartan cilexetil. Stability studies showed that proniosomal gel formulation was stable throughout its study period.
Conclusion: Physiochemically stable Candesartan cilexetil proniosomal gel was formulated, which could deliver significant amount of the drug across the skin in a steady-state manner for the prolong period of time in the treatment of hypertension.
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