Study On Compound Testoterone Propinonate Ointment

Objective:Testosterone propionate is the first choice for current treatment of female genital lichen sclerosis, ointment is a common dosage form in hospital preparation, and this dosage form hasn’t the "first pass effect" and the unique advantages of gastrointestinal damage. It can reduce drug toxicity and side effects, stable, long-lasting plasma concentration, improving efficacy, reduce delivery times, and convenient administration. The aim of this research is to study on compound testoterone propinonate ointment, and to establish ointment transdermal absorption model and quality control standards, and to investigate its stability.Methods:At first homogeneous design Us*(85) and orthogonal design1,9(43) was carried out in order to choose the proportion of glyceryl monostearate, stearic acid octadecanol, liquid paraffin and white vaseline in oil phase. The response of the experiment include:color, texture, moisturizing and feel, thin consistency, coated the ductility, comfort, size and stability. Investigate the impact of the different state of the oil phase to finalize the optimum ratio of ointment. Calculate of the HLB value that emulsifying the oil phase, determine the prescription of the final amount of water phase. Using the study of transdermal enhancers effective instrument to determine transdermal drug, and accumulating by the amount of testosterone propionate for evaluation, and use of uniform design method to find optimal transdermal enhancers and join ratio. Finally, we can be prepared optimal prescription ointment.Reference to 《the State Food and Drug Administration guidelines for stability of new drugs》 and the actual situation and the stability tests, the bulk drug and oinment with acid, alkali, strong oxidizing conditions of stability and strong light, high temperature, high wet on the preparation of, and had some accelerated tests and long-term test.Results:The uniform design and orthogonal was designed to determine usage per100g cream together the oil phase containing monoglycerides3.5g, stearic acid2.75g, octadecanol0.75g, liquid paraffin3.25g, white vaseline1g; emulsify the oil phase required HLB of11.08, the water phase containing triethanolamine0.9g, sodium dodecyl sulfate0.79g. By (25±2) g Kunming mouse skin to normal saline soaked overnight to remove the impurities, with30%ethanol-normal saline solution as the receiving medium to determination of the skin by the cumulative amount of testosterone propionate, uniform design analysis methods to determine the order of azone1.2g, propylene glycol7.7g, menthol combination of0.05g of transdermal penetration enhancers can be achieved by adding agent.HPLC methodology was reliable and stable. Determination of the substances are used RP-HPLC, mobile phase was methanol:water (85:15), flow rate0.8ml·min-1, detection wavelength was247nm, measured the preparation of small quantities of this product that the content label amount was98.0%～102.0%, the determination of related substances had satisfactory results.. Cumulative transdermal absorption of testosterone propionate used Franz diffusion cell proliferation of devices, rotor speed is400r·min-1, the temperature of circulating water bath was37℃.Bulk drugs and testosterone propionate ointment are unstable under the condiction of acids, alkalis and strong oxidizing factors, the results showed that:at high temperature (30℃), humidity (75%±1%) conditions, the ointment had no content significant changes, when the ointment at the condition of high temperature (60℃), humidity (92.5%) and strong light conditions, both influent the stability of compound testosterone ointment, suggesting that the ointment should be sealed in packaging, dark cool place. Agents has to use airtight package, dark cool place, accelerated testing and long-term stable under the experimental conditions.Conclusion:The selected optimal preparation and the formulation of testosterone propionate ointment has good process conditions, characters, and transdermal quickly. UV method is simple, accurate and can be used for primary percutaneous absorption of drug content. HPLC is specific, easy to use, can be used for determination of testosterone propionate and related substances.