Formulation development and evaluation of drug-in-adhesive-type transdermal patch of metoclopramide HCl

Abstract

The objective was to design and develop a drug-in-adhesive-type transdermal patch formulation of metoclopramide HCl, which is used as an effective antiemetic, dopaminergic antagonist agent. In DIA patches, drug is directly embedded in the polymeric adhesive layer and permeates through the skin to provide systemic effect, avoiding gastrointestinal tract complications, including the first-pass metabolism. Six different patch formulations were prepared by a solvent evaporation method using varying metoclopramide HCl concentrations using acrylate polymer DURO-TAK® 387/2510 for adhesive support. In vitro permeation profiles and parameters were obtained by using the skin of hairless albino Wistar rats. The influence of drug content on the rate of permeation was investigated, and patch formulation was optimized based on Q12, flux, and lag time. The effect of permeation enhancers (EO and PG) on the permeation rate of metoclopramide HCl was also studied. The skin irritation study was performed to observe the hypersensitivity against the patch component. Stability studies of the optimized formulation of a transdermal patch for three months at three different temperatures were investigated. The transdermal patch formulation containing 10% w/w metoclopramide HCl was capable of effectively delivering metoclopramide HCl for systemic effect without any skin irritation. It has Q12 of 3.892 ± 0.0043 mg/cm2, flux rate of 0.2501 mg/cm2 h, and the coefficient of permeability of 6.25E−02 cm/h with a lag time of 0.442 h. The stability data revealed that the optimized patch formulation could be stored at 4 °C in the refrigerator with a shelf life of 3.53 months. This newly developed metoclopramide transdermal DIA patch is an effective alternative to oral delivery with desirable antiemetic activity.