Azadirachita indica gum based sildenafil citrate mucoadhesive microspheres – Design and optimization

Abstract

The current research involved design and optimization of Sildenafil citrate loaded oral mucoadhesive multiparticulate system, to prolong residence time and enhance bioavailability of the drug. The microspheres were prepared by ionotropic gelation method using ‘Azadirachta Indica’ as a mucoadhesive polymer employing 32 factorial design. Microspheres were discrete, spherical, free flowing and the absence of drug-excipient interactions was confirmed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. The drug release followed Fickian diffusion mechanism with zero order release kinetics. Optimization of the responses was carried out using numerical desirability and graphical approaches. In vivo pharmacokinetic studies in rabbits demonstrated an increase in mean residence time by 75% and relative bio-availability by 1.5 times. Ex vivo wash off test and radiographic studies in rabbits confirmed the adherence of the microspheres to the GI mucous layer which were retained for an extended period of time. The developed formulation can be a viable alternative to the conventional dosage forms of thrice a day dosing in pulmonary arterial hypertension. The research signified the potential of ‘Azadirachta Indica’ as a mucoadhesive polymer in the design of oral controlled drug delivery systems.