Hydroxy propyl β-cyclodextrin complexation of promethazine hydrochloride for the formulation of fast dissolving sublingual film: in vitro and in vivo evaluation

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) of drug was developed. FDSF was formulated using pullulan and propylene glycol (PG) by solvent casting method. Complete taste masking was successfully obtained with HP β-CD, aspartame and grape fruit flavour. Complex of drug was proved using Fourier transfer infrared spectroscopy, differential scanning calorimetry and X-ray diffraction studies. Optimization of concentration of pullulan and PG was done using 32 full factorial design. Batches were evaluated for the parameters like elongation, tensile strength, folding endurance and in vitro disintegration studies. In vitro dissolution indicated 100 % drug release within 7.5 min. Environmental scanning electron microscopy studies also showed uniform drug distribution and integrity of film. In vivo sublingual absorption in human indicated that 70 % of drug absorbed in 10 min. The stability studies indicated that label should state “Store at cool, dry place” at temperature 25 °C. So by formulating the taste masked FDSF of PMZ-HCl will give faster onset of action and avoid unnecessary drug intake leading to traveller friendly formulation.