Development of Nifedipine Transdermal Drug Delivery System Using Gelling Agents as Matrices

Abstract

Nifedipine transdermal drug delivery systems were developed by using Pluronic F-127 as hydrophilic gelling agent and Aerolsil A-200 hydrophobic gelling agent. Organic modifiers ; glycerol, propylene glycol ; co-solvent : polyethylene glycol 400; and thickening agent : Aerosil A-200, hydroxypropylmethyl cellulose were used varying concentrations to modify the physical characteristics of both types of gel matrices. The desired preparations, suitable physical appearance gel matrices, were assessed the in-vitro skin permeation of nifedipine by using modified Keshary-Chien diffusion cells, miniature pig’s skin as barriers, and HPLC method. The release mechanism and effects of additives were elucidated. The results indicated that Pluronic F-127 gel matrices and Aerosil A-200 gel matrices could exhibit sustained release of nifedipine Over 24 hours. The possibility of nifedipine release mechanism of both types of gel matrices would be non-diffusion. For hydrophilic gel matrices, the preparations composed of high concentration of organic modifier provided greater skin permeation rate than the preparations composed of low concentration of modifier. For the preparations contained both organic modifier and co-solvent, the higher concentration of co-solvent-containing preparations exhibited greater skin permeation rate than the lower concentration of co-solvent-containing preparations. For the hydrophobic gel matrices, the higher skin permeation rate was achieved from the low concentration of organic modifier containing preparations. The skin permeation rate achieved from the preparations contained both of organic modifier and co-solvent was high for the preparation contained high concentrations of polyethylene glycol 400 and propylene glycol. However, the skin permeation rate was slow for the preparation contained high concentrations of polyethylene glycol 400 and glycerol. The thickening agent containing preparations retarded the skin permeation rate compared to no thickening agent containing preparations. In summary, the preparation with highest skin permeation rate studied composed of 50% w/w Pluronic F-127, 10% w/w glycerol and 6% w/w Aerosil A-200. The skin permeation kinetic and release mechanism of this gel matrices was zero order kinetic model and non-diffusion or erosion of matrix, respectively. This gel matrix could control and exhibit a constant and high skin permeation rate over periods of study that could be used to modified for a-once-daily medication of angina pectoris and/or hypertension.