Development of Promethazine Hydrochloride Mucoadhesive Patches for Buccal Delivery: In vitro, Ex vivo and In vivo Characterization

Abstract

Promethazine hydrochloride (PMZ HCl), an antiemetic, undergoes extensive first-pass metabolism (bioavailability 25%). The purpose of the present investigation was to develop mucoadhesive patches for transbuccal delivery of PMZ HCl using solvent casting technique with Hydroxy ethyl cellulose (Natrosol 250 E) and hydroxylpropyl methyl cellulose as mucoadhesive polymers and propylene glycol as the plasticizer and evaluate their physicochemical characteristics, in vitro drug release, moisture absorption, surface pH, mechanical properties, in vitro bioadhesion, in vivo residence time, and ex vivo drug permeation through porcine buccal membranes from optimized buccal patch and stability studies. The physicochemical interaction between PMZ HCl and polymers was investigated by Fourier Transform Infrared Spectroscopy. Ex vivo drug permeation through porcine buccal membrane was performed and 83.7% of the drug permeated in 6 hours with flux 0.19 mg h–1cm–2. The optimized formulation AA4 showed maximum drug release (98%) in 6 hours in the Higuchi model release profile. Moisture absorption, surface pH, tensile strength, elongation at break, peak detachment force and work of adhesion values of the optimized formulation were found to be 68.1%, pH 6.7, 12.3 kg/mm2, 69.2 % mm2, 7.5 N and 2.73 mJ respectively. Formulation AA4 showed 77.6% of the drug permeated through porcine buccal membrane in 6 hours and flux calculated to be 0.45 mg h–1cm–2. FTIR studies showed no evidence of interaction between the drug and polymers. In vivo mucoadhesive behaviour of the optimized formulation was studied in healthy human volunteers and subjective parameters were evaluated. The stability of the optimized formulation was studied and no significant changes were detected in drug content, in vitro release and ex vivo permeation after 6 months.