Formulation, Optimization And Characterization Of Sublingual Dosage Forms Of Promethazine Hydrochloride

Abstract

Promethazine hydrochloride (PMZ HCl) is a classical anti-motion sickness drug which has oral bioavailability (25%) due to extensive hepatic first pass metabolism. To overcome this drawback, novel, fast dissolving sublingual film (FDSF) and tablet (FDST) of PMZ HCl was developed. FDSF was formulated using pullulan as polymers and propylene glycol as plasticizer by solvent casting method. Complete taste masking was successfully obtained in batch containing PMZ HCl:HP β-CD(1:1) drug: aspartame (1:1) and grape fruit flavour was added to the complex, bitter after-taste of PMZ HCl was successfully masked. Complex of drug was proved using FTIR, DSC and XRD studies. Optimization of concentration of Pullulan and PG was done using 32 full factorial design. Optimized Batch F8 was evaluated for the parameters like elongation, tensile strength, in vitro disintegration and in vitro dissolution and where found within acceptable range. Environmental Scanning Electron Microscopy studies also showed uniform drug distribution and integrity of film. FDST were formulated using optimization of different diluents and superdisintegrants. To achieve the desired disintegration time ratio of PMZ HCl:HP β-CD was reduced to 1:0.75 and L-HPC(15%) was used, friability was controlled using PVP K-30. Optimized Batch M25 complies all the pre and post compression parameters. The kinetics of in vivo drug absorbed in human volunteers indicated that about 70.18% of the drug was absorbed from sublingual film and 52.72% from the tablet within 10 min. Comparative drug release, disintegration time and permeation studies indicated that FDSF had more promising result than FDST. The stability studies indicated that label should state “Store at cool, dry place” at temperature 25°C. Thus the developed FDSF formulation was Traveller Friendly.