Formulation and evaluation of fast dissolving sublingual film of Buspirone hydrochloride

Abstract

Buspirone hydrochloride (BUS) is a classical anti-anxiety drug which has oral bioavailability (5%) due to extensive hepatic first pass metabolism. To overcome this drawback, novel, fast dissolving sublingual film of Buspirone HCl was formulated using Polyox WSR N-10 and PVP K-30 their composite as polymers and propylene glycol as plasticizer by solvent casting method. Complete taste masking was successfully obtained in batch CD18 due to ternary complexation between BUS, β-CD, PVP K-30. When sweetener was added to the ternary complex, bitter after-taste of Buspirone HCl was successfully masked. Optimized batch F 10 contained 3% w/v of Polyox WSR N-10 and 2% w/v PVP K-30 with propylene glycol at concentration of 20% weight of polymer, BUS: β-CD (1:1.5 molar ratio), BUS: sucralose (1:0.5 ratio) and 0.15 ml orange flavor which was casted on teflon surface using water as solvent. Batch F10 was evaluated for the parameters like elongation, tensile strength, in vitro disintegration and in vitro dissolution. In vitro permeation study was done using Rabbit sublingual mucosa model and it was found that the drug was more permeable at the ventral surface (P=4.28×10-3) than at the floor of the mouth (P= 3.24×10-3). In vivo absorption studies in rabbits reveals that 50.274 ± 5.235 % of Buspirone Hydrochloride was absorbed sublingually from film within 5 minutes. The kinetics of in vivo drug absorbed from sublingual film in human volunteers (two) indicated that about 51.40±3.285 % of the drug was absorbed in 5 min and 56.12±2.60% of the drug was absorbed in 10 min from the film. From the ANOVA analysis it was found that Fcal value (0.096997) is less than F crit (5.987378) which indicates insignificant difference between two parameters viz. ex-vivo rabbit mucosa & in-vivo human drug absorption study. The stability studies were conducted at 40°C/75% RH. It was observed that film became brittle and light in colour after 1 month. At 25°C/60% RH, the films showed good stability in terms of flexibility, acceptable colour, mechanical property, with slight change in in-vitro disintegration time.