Abstract

FORMULATION AND EVALUATION OF NEBIVOLOL HYDROCHLORIDE SUBLINGUAL TABLETS BY USING IN SITU MICROCRYSTALS

Udaykumar B. Bolmal*, Srushti D. Mali and Rajashree S. Masareddy

Abstract

The present study was aimed to formulate and evaluate Nebivolol hydrochloride sublingual tablets using in situ microcrystals to enhance the dissolution rate. It is a third generation β adrenergic blocker mainly used for hypertension treatment and belongs to BCS class-II drug. It’s a very potent drug but the problem associated with this is a low solubility of drug leads to low dissolution and variable bioavailability. By changing 3 variables each two levels, eight formulations were prepared with full factorial design. In situ microcrystals were formulated by using poloxamer and Rhamnolipid as stabilizing agents by solvent change method. FTIR, DSC, SEM, and XRD studies were carried out for investigation of interaction with excipients, particle morphology, and crystallinity of drug respectively. Formulation M7 was considered as optimal showing the lesser particle size (2.57μm) and enhanced in vitro dissolution (84.33%) in comparison with an untreated drug. Sublingual tablets were formulated to enhance the poor oral bioavailability of drug due to extensive first-pass metabolism by CYP P450 2D6. Tablets were prepared by incorporating in situ microcrystals along with a different concentration of superdisintegrant (SSG, crospovidone) by direct compression method. Formulation F7 was considered as optimal with disintegration time up to 13.66 seconds. In vitro dissolution and in vitro permeation were found to be 98.57% and 82.99% respectively within 30 minutes. Thus, it can be concluded that the sublingual tablet containing Nebivolol hydrochloride in situ microcrystals seems to be a promising formulation for safe and effective delivery via sublingual route for the treatment of hypertension providing faster action.

Keywords: Sublingual tablet, In situ Microcrystallization method, Nebivolol hydrochloride, Poloxamer 188, Rhamnolipid.