The Preparation And Quality Research Of Compound Clobetasol Propionate Ointment

Clobetasol propionate compound ointment is a compound preparation containing 0.05% clobetasol propionate and 0.025% tretinoin.It has anti-inflammatory and anti-dermal keratinization effects,which is used in the treatment of psoriasis vulgaris.The combined use of the two drugs has a synergistic effect of additive or enhanced efficacy and no antagonism,which could reduce drug dependence and adverse reactions and improve patient compliance.The thesis took the reference preparation as a reference and mainly conducted research from the direction of pharmaceutical preparations and drug analysis to develop a stable and controllable compound preparation.Based on the reference formulation prescription,the key quality attributes such as formulation characteristics,spreadability,microstructure and physical stability were used as indicators to conduct prescription research.The types of excipients were screen to determine the composition of the prescription;investigated the amount of excipients to confirm the impact on the ointment;performed orthogonal experiment design to optimize the prescription.In terms of process research,the key process parameters of homogeneous emulsification speed and time,phase mixing temperature,etc.were studied to determine the final preparation process.The quality standards were formulated with reference to the relevant pharmacopoeia standards.Established high-performance liquid chromatography analysis method for the determination of content and related substances and verified methodologically.Tretinoin and clobetasol propionate showed a good linear relationship in the concentration range of 5.04?15.11 ?g/ml and 10.26?30.77 ?g/ml,respectively.Recovery rate and precision met the requirements.The related substance methodology research showed that the method could effectively separate impurities with good specificity.The quality research of compound clobetasol propionate ointment was carried out to deternine the quality standards,with the stability of accelerated and long-term tests.In accelerated test(temperature 40? ± 2?,RH 75% ± 5%)for 6 months,the content and related substance were within the specified range;There was no significant change in all indicators under long-term test(temperature 25? ± 2?,RH60% ± 10%)is investigated 12 Months.The stability results showed that the product is basically stable and the quality is stable and reliable.Finally,the in vitro percutaneous permeability and safety research of compound clobetasol propionate ointment were studied.In vitro transdermal studies found that there was little amount of compound in the receiving solution through the skin within 24 hours,but retained in the skin,meaning that the product can effectively produce local effects and avoid systemic effects.The drug retention of self-developed products was higher than that of reference preparations,which may have better efficacy.Preliminary safety research results indicated that this product had no irritation to rabbit skin and may have better safety.