Formulation, optimization and evaluation of oral nanosuspension tablets of nebivolol hydrochloride for enhancement of dissoluton rate

摘要

Nebivolol hydrochloride is a poorly water soluble drug falls under class II biopharmaceutical classification system, which is beta;1 receptor antagonist that leads to vasodilatation, decreased peripheral vascular resistance, lowers blood pressure and heart rate. The rate of its oral absorption is often controlled by dissolution rate in the gastro intestinal tract. The aim of the present investigation was to improve the solubility and dissolution rate of poorly soluble drug, nebivolol hydrochloride by nanosuspension tablet prepared using microcrystalline cellulose PH101 (MCC) as diluent, povidone k 30 as binder and croscarmellose sodium as disintegrating agent. The formulation development work was performed by wet granulation method. The prepared granules and tablets were evaluated for various pre and post compression parameters as per IP and all the formulations are as per standards. Nebivolol nanosuspensions were prepared using solvent displacement/nanoprecipitation method. Among all the formulations F6 formulation has given the best dissolution studies (98.93) and disintegration time (12.80 sec). In-vitro dissolution studies showed maximum (98.93) release of drug within 15 minutes (F6) and mechanism of drug release from the tablets was followed first order kinetics. The optimized formulation (F6) is further selected and compared with the in-vitro drug release of innovator product (Nebilet) it showed 98.37 release of drug within 60 minutes and pure drug 27.34 within 60 minutes. Enhanced drug release rates were observed by nanosuspension tablets when compared to pure drug and innovator product (Nebilet). The physicochemical compatibility of the drug and excipients were studied by infrared spectroscopy and differential scanning calorimetry. The crystalline state of nebivolol hydrochloride drug state was changed to amorphous state due to nanosuspension formation and was confirmed by powderd X-ray diffraction study. Fourier transform infrared spectroscopy results revealed that there was no interaction between drug and excipients and results showed that there were no known chemical interactions of drug with excipient in formulation. It is concluded nanosuspension tablets were successfully prepared and they have demonstrated dramatic improvement in dissolution rate of the active drug.