Research On Prepartion And Kinetics Of Dapsone Inclusion Compound Gel

Background: Dapsone,4,4’-Diaminodiphenylsulfone, is sulfonescompound to be effective in leprosis mycobacteria,anti-inflammatory and anti-immunity properties. It has beentreated as classic medicine in the treatment of leprosy anddermatitis herpetiformis. It also has been used in the oraltreatment of several of dermal diseases. However the high plasmaconcentration may bring about adverse effects, especiallyhematological side effects including hemolysis andmethemoglobinemia. The dosage of dapsone should be taken moreattention. Researchs had showed the systemic exposure was only onepercent by a gel dermal application compare to oral administration.Dapsone, which was difficult solved in water, would be informed intoaqueous gel, so it needs to utilize inclusion technology to makedapsone into inclusion compound helping to improve solubility.Using cyclodextrin inclusion compound as a carrier was made intoadpsone aqueous gel.Method: To establish the assay method of dapsone inclusioncompound by ultraviolet spectrophotometry was accurate andreliable. The multiple factor and levels experiments were done by orthogonal design and tatistical analysis with the drug entrapmentefficiency and yield as criteria. To optimize preparation ofdapsone inclusion compound ensure the molar ratio, reaction timeand reaction temperature. Using ultraviolet spectrophotometry,infrared spectrometry, microscopic observation and differentialscanning calorimetry methods confirmed dapsone inclusion compound.In vitro gelrelease was assessed using a semipermeable membranesand assay method of resultant release was established byultraviolet spectrophotometry. Percutaneous permeation in vitrowas undertaken by using analog Frans diffusion cells.Assay methodof by HPLC and experimental condition of percutaneous permeationwas established. Having been prepared gels containing1%or2%dapsone inclusion copmpund or2%dapsone were going on percutaneouspermeation and release test in vitro to compare pharmacokineticprofiles among the three kinds of gels. The drug content would beensured by accumulated release amount in vitro and steadypenetration rate and accumulative penetration in vitro as standard.Optimized dapsone inclusion compound gel would be going onstability test including influential test and accelerated test.Conclusion: The perfect preparation conditions were as follow:the molar ratio of dapsone to β-cyclodextrin was1:1, the reactiontemperature was80degree and the reaction time was3hours. Theinclusion compound was white and fluffy powder, soluble in waterand it had been confirmed. Three batches of inclusion compoundprepared by perfect conditions were repeated and gained a moderateentrapment rate. Dapsone inclusion compound gel content wasconfirmed by release and percutaneous permeation of it in vitro.Gel containing1%drug could be releasing rapidly and penetrating lessly to be available for dermal disease. The content and relatedsubstance of gel was up to standard in stability analysis.Appearance of gel was colorless, transparent and not shrivelledwhile3months of accelerated test.There was not apparently changein pH since accelerated test. The storage condition of gel shouldbe at a regular temperature to avoid more related substanceproducing in a high temperature.