DESIGN AND DEVELOPMENT OF NOVEL MICROEMULSION BASED TOPICAL FORMULATION OF HESPERIDIN
Keywords:Hesperidin, Bioflavonoid, Venous disease, Microemulsion, Topical, In-vivobioavailability
Objective: Bioflavonoid hesperidin is used primarily to assist treatment of capillary disorders like hemorrhoids and varicose veins, by reducing capillary permeability. There are certain limitations to the use of these bioflavonoid in the pharmaceutical formulations because of their physical properties like limited aqueous solubility, poor bioavailability and high oral dose. Therefore in the present research work micro emulsions of hesperidin were developed for improving solubility and bioavailability using topical route.
Methods: Micro emulsions of hesperidine were prepared by plotting pseudo ternary phase diagram using eucalyptus oil, Tween 80, AccononCC6 and water. The micro emulsion with optimized droplet size, polydispersity index and ex vivo diffusion ability was then converted into the ointment for ease of application. Droplet size and Polydispersity index were obtained by using Photon correlation spectroscopy. Optimized o/w microemulsion of hesperidin composed of eucalyptus oil 20%, Tween-80/Acconon CC-6(2:1) 33% and water was then converted into ointment using optimized ointment base. [a1]Â The microemulsion loaded ointment was then characterized for physicochemical parameters. Ex-vivo permeation and In-vivo bioavailability studies were carried out to check the r. release profile of drug from the prepared formulations.
Results: It was observed from ex-vivo permeation studies that flux value for optimized microemulsion was found to be 8.971Âµg/ml/cm2as compared to pure hesperidin (1.230 Âµg/ml/cm2). This formulation was then converted into ointment by using optimized base containing PEG-6000, PEG-400 and Cetyl alcohol. This microemulsion based ointment passed all the characterization tests (droplet size analysis using PCS, ex-vivo permeation studies, in-vivo bioavailability studies etc.) as well as remained stable for the period of 3 mo during stability studies as per ICH guidelines. The bioavailability studies of hesperidin microemulsion based ointment in rats showed 3 fold statistically significant (p<0.001) improvement in bioavailability as compared to microemulsion when applied topically.
Conclusion: Thus it can be concluded that components of microemulsion and ointment are contributing to improve bioavailability of hesperidin.
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