Quality And Stability Research Of Triamcinolone Acetonide And Econazole Nitrate Dermal Patch

Triamcinolone acetonide (TO) and econazole nitrate (ECZ) dermal patch is a kind of compound formulation which can be used to treat topical dermatitis. Quality researches could provide the basis to establish quality standards and to comprehensively and effectively control the quality of a formulation. According to the Chinese Pharmacopoeia (2010) and the technical guidance from CDE, the patch quality control methods were established, including the determination of drugs content, the determination of residual solvents and the test of microorganisms.Firstly, the researches on substance included the high performance liquid chromatography (HPLC) methods of the two drugs, solubility in different solvents and the forced degradation behavior. By analyzing the drugs stability in commercial formulation (Pevisone cream) and according to the characteristics of a dermal patch, surfactants (pegoxol-7 Stearate, etc) were used as penetration enhancers to study the stability of drugs mixing with excipients at high temperature. We chose an acrylic pressure-sensitive adhesive (PSA) as matrix and investigated the influence of propylene glycol, isopropyl myristate (IPM) and polyvinylpyrrolidone (PVP-K30) to the compatibility of drugs and the PSA. The results indicated that ECZ has good solubility in alcohols and the two drugs both are unstable under alkaline conditions. Two drugs have good compatibility with PSA, poor compatibility with IPM and PVP-K30 and adding penetration enhancers had no significant effect on the pharmaceutical stability.Secondly, the quality of patch were studied. We established HPLC to determine the content of the patch TO-ECZ. Chromatographic conditions were as follows:Instrument: Shimadzu LC-20A liquid chromatograph. Column:Mitimate XB-C18 (4.6×250 mm,5μm); mobile phase:TO methanol=67:33 (v/v), ECZ methanol= 86:14 (v/v); flow rate:1.0 mL/ min; column temperature:30℃; detector:diode array detector; detection wavelength:TO is 240 nm, ECZ to 230 nm. This method is specific, accurate, durable and suitable for TO-ECZ patch determination. Dissolution experiments were measured by using in vitro release of the patch. The release of the two drugs is excellent in uniformity, TO substantially completely released in 1 hour (approximately 90%) and ECZ 3 hours release can reach more than 60%. This method also applies to the release of the patch and ECZ TO Measurement. We established a gas chromatography method to detect residual solvent of the patch and adopted FFAP capillary column and temperature programmed to separate three kinds of residual solvents. This method is specific, accurate, and suitable for using to efficiently concentrate to limits and detecting TO-ECZ three kinds of residual solvents. We established a microbiological examination method using the plate method to carry out technical inspections of bacteria, membrane filtration method for fungi and mold count checked. The recoveries were greater than 70% for TO-ECZ patch microbiological examination.Finally, we studied the stability of the patch. We adopted the classical constant temperature method, by TO-ECZ patch drug degradation rate constant at different temperatures using Arrhenius equation to simulate index, calculate the optimal preservation conditions TO-ECZ patch.