Research On Dapsone-β-cyclodextr Inclusion Compound Gel

Research Background:dapsone is a class of aniline derivatives. Today, dapsone is the only sulfone drugs retained so far for the treatment of human disease.It was compound in1908, for the treatment of leprosy from1947, successed in treatment of dermatitis herpetiformis in1950, later it was often alone or combined with other drugs used to treat non-infectious skin disease treatment. In recent years, researcher discovered it has about1mg/ml of minimum inhibitory concentration for Propionibacterium acnes and has a strong anti-inflammatory effect.So the United States made topical gel (Aczone) for the treatment of moderate to severe acne and achieved good efficacy in clinical. Currently there are still no this type of dapsone preparation. Acne often occured on the face, from the point of easy to use and reduced drug toxicity and considered the physical and chemical properties of dapsone and clinical needs we want to prepared dapsone-β-cyclodextr inclusion compound gel with sustained release gel on the basis of foreign. Investigate the element and the process of the prescription to select the best prescription and to study out the quality standards of the prescription.Methods:During the prescription process,firstly,to delay the release of the drug we used the β-cyclodextr to made dapsone-β-cyclodextr inclusion compound. UV-visible spectrophotometry was esstblished for studies of the dapsone-β-cyclodextr inclusion compound.On the basis of single factors design experiment, c the encapsulation efficiency to select temperature and time of the inclusion compound and determine the best prescription. At the same time, according to the encapsulation efficiency to select the process of the prescription. Secondly, High Performance Liquid Chromatography was established for studies of dapsone-β-cyclodextr inclusion compound gel. According to the traits, appearance, stability and on the basis of single factors design experiment,use the visible indicators to preliminary investigation the prescription, through the steady-state transdermal rate of transdermal test as an indicator to select the best prescription.During the study on quality standard, According to appendix of Preparations General Principles I Q of《Chinese Pharmacopoeia))(2010) to establish the character, identification, pH, related substances and determination of content of gel.Conclusion:We determined the best inclusion condition was:ratio of the material1:1, temperature60℃, time2h. The dapsone-β-cyclodextr inclusion-compound is white, fluffy powder. The UV-visible spectrophotometry is used to the determination of inclusion content of dapsone and the advantage of this method is instrument is simple, easy operation, short analysis time.In single factors design experiment,high molecular polymer carbopol940was selected as base gel because of reasonable viscosity,16%DMSO was selected as solvent after considering the preparation stability and DMSO dosage as possible as low. Through full-scale testing to select the glycerol, propylene glycol as moisturizing agents and potential solvent, triethanolamine as pH adjusting agent, ethylparaben as preservatives. We established the HPLC for studies of dapsone-β-cyclodextr inclusion compound gel and HPLC for studies of transdermal test.According to the visible indicators like physical appearance, stability determined use the glycerol,1,2-propanediol as potential solvents and moisturizers.Through the steady-state transdermal rate of transdermal test as an indicator to select the best prescription was:carbomer-9401g;DMSO16g;1,2-propanediol10g;glycerol5g, ethylpar-aben0.1g;appropriate amount of triethanolamine. And through the transder-mal test we found with the time prolonged the increase of drug released and still released after22h,we concluded that dapsone-β-cyclodextr inclusion compound gel has the role of slow release. The dapsone-β-cyclode-xtr inclusion compound gel is a colorless, transparent, uniform semi-solid dosage forms. The HPLC is used to the determination of dapsone-β-cyclodextr inclusion compound gel content of dapsone and this method is Specific, accurate, stable and reliable.