Study On Amorolfine Hydrochloride Cream Based On O/W Emulsions Matrix

In recent years, the phenomenon of fungal infections in clinical has been more and more prominent, and fungal infections are more stubborn and dangerous. Coupled with antifungal drugs' susceptibility to several antifungal drugs, so it is urgent to develop new antifungal drugs. Amorolfine hydrochloride is a new broad-spectrum antifungal drug with antifungal activity. Amorolfine hydrochloride has good curative effect to cure locally superficial fungal infection and also has the advantages of easy carryover, low recurrence rate and less side-effect, etc. Therefore, which applies amorolfine hydrochloride to clinical brings the Gospel to the local treatment for patients facing adverse reaction in the systemic treatment. We prepared amorolfine hydrochloride cream with the carrier of O/W emulsion matrix and amorolfine hydrochloride as the model drug. We have confirmed the preparation process and the prescription of amorolfine hydrochloride cream, established quality standard of amorolfine hydrochloride cream, examined the stability of amorolfine hydrochloride cream, researched the in vitro determination of retention of amorolfine hydrochloride cream via pig skin penetration. We have laid the foundation for the decalaration for new drug of treating superficial fungal infection by studying the preparation process, prescription, quality standard, stability and the in vitro determination of retention of amorolfine hydrochloride cream. The main study about the article can be summarized as follows:1 The study on the preparation process and screening the prescription of amorolfine hydrochloride creamObjective: To optimize the procedure of preparing amorolfine hydrochloride cream and prescription of amorolfine hydrochloride cream. Methods: To optimize the best preparation process of cream by processing water phase and emulsifying ways. Single factor method is used to screen the material's amount including oil phase, preservative and the dosage range of emulsifier, auxiliary emulsifier and carbomer 980, then the optimization of the formulation could be achieved by the central composite designresponse surface methodology. Results: The best preparation process of amorolfine hydrochloride cream: to preparate the cream by using the preparation method of emulsifier in the aqueous phase, preparation temperature 80 ?, emulsifying time 30 min, the stirring speed 600 r/min. The determinate best prescription is Stearic acid hydrocarbon oxygen 40 ester as the emulsifier, octadecanol as auxiliary emulsifier, carbomer 980 as the main viscous agent. Conclusion: The method of preparation is simple, easy to control; prescription optimization is reasonable and has good stability and is accordance with the cream preparation requirements.2 The study on quality standards of amorolfine hydrochloride creamObjective: To control the quality of amorolfine hydrochloride cream. Methods: The traits, identification, examination(including p H value, amount and particle size) and viscosity index are reviewed, and HPLC determination of amorolfine hydrochloride cream was established. Results: All the indexes of amorolfine hydrochloride cream conform to the requirements of the Chinese pharmacopoeia about creams. The method for the determination of amorolfine hydrochloride cream are an Diamonsil C18 column(150 mm×4.6 mm,5 ?m) with mobile phases of methanol-ammonium dihydrogen phosphate solution(adjusted p H to 3.0 with phosphoric acid)(70:30). The flow rate was 1.0 ml·min-1. The detection wavelength was 214 nm. Column temperature is 30 ° C. Conclusion: stablished quality standards of amorolfine hydrochloride cream provides basis for the establishment of its quality standards.3 The study on the stability of amorolfine hydrochloride creamObjective: Investigate the stability of amorolfine hydrochloride cream. Methods: Make the stability test according to the project stipulated by Chinese pharmacopoeia(edition 2015)9001 on drug substance and drug stability test preparation guidelines. Results: The determination of cream didn't change significantly and was in line with the relevant provisions of the Chinese pharmacopoeia and meet the basic requirements of cream preparation. Conclusion: The preparation stability is good, and high temperature should be avoided during the storage.4 The study on the in vitro determination of retention of amorolfine hydrochloride cream via pig skin penetrationObjective: To research the in vitro determination of retention of amorolfine hydrochloride cream via pig skin penetration. Methods: The experiments on in vitro pig skin penetration were performed by modified Franz's cell using Bama miniature pig skin. After being extracted with 90% acetonitrile solution, samples were separated by HPLC method on an Diamonsil C18 column(150 mm×4.6 mm,5 ?m) with mobile phases of methanol-ammonium dihydrogen phosphate solution(adjusted p H to 3.0 with phosphoric acid)(70:30) and ketoconazole as an internal standard. The flow rate was 1.0 ml·min-1. The detection wavelength was 214 nm. Results: Calibration curve for amorolfine hydrochloride was linear in the range of 1.13~8.05 ?g·ml-1. The average recoveries of low, medium and high concentration were(105.48±2.58)%,(99.46±1.79)% and(101.41±2.00)%, respectively. Precision is good(RSD=1.36%). The limit of quantification and detection was 6.73 ng·ml-1 and 2.71 ng·ml-1, respectively. Conclusion: The method has good specificity, high accuracy and good reproducibility. The method can be used for skin bioequibalence study related to amorolfine hydrochloride cream.