Preparation and Evaluation of Pranoprofen Gel for Percutaneous Administration

Abstract

ABSTRACTThe percutaneous delivery of nonsteroidal anti-inflammatory drug (NSAID) has the advantages of avoiding the hepatic first pass effect and delivering the drug to the inflammation site at a sustained, concentrated level over an extended period of time. Hydroxypropyl methylcellulose (HPMC) and poloxamer 407 were used in an attempt to develop new topical formulations of pranoprofen. The effects of the drug concentration (0.04, 0.08, 0.12, 0.16, and 0.20%) on the rate of drug release from HPMC-poloxamer 407 gels were examined using a synthetic cellulose membrane at 37±0.5°C. The rate of drug permeation increased significantly with increasing drug concentration in the gels until the concentration reached 0.16%, and increased slightly thereafter. The effects of temperature on the rate of drug release from the 0.16% pranoprofen gels were evaluated at 32, 37, and 42°C. The rate of drug release from the 0.16% pranoprofen gels increased with increasing temperature with activation energy (Ea) of 8.88 kcal/mol. Various penetration enhancers, such as nonionic surfactants and fatty acids, were incorporated in the gel formulation in an attempt to increase the level of drug permeation. Among the enhancers used, octanoic acid had the strongest enhancing effects with an enhancement factor of 3.09. The anti-inflammatory effect of the pranoprofen gel was evaluated using a rat paw-edema model. The 0.16% pranoprofen gel containing octanoic acid as an enhancer reduced the edema size by approximately 73% compared with that of the control group. These results highlight the feasibility of a topical gel formulation of pranoprofen containing an enhancer.