Research On Dapsone Microemulsion And Its Gel

Objective In this paper,5%dapsone microemulsion and microemulsion-based hydrogel are studied.The main research contents include:research on the formulation of dapsone microemulsion,investigation of the physical and chemical properties of dapsone microemulsion,development and quality research of dapsone microemulsion-based hydrogel,irritation evaluation and preliminary stability study of dapsone microemulsion-based hydrogel.This study aims to improve the solubility and transdermal penetration of dapsone,and to provide a stable,controllable,high drug-loading microemulsion-based hydrogel for the transdermal administration of dapsone.Methods The microemulsion formulations were screened by measuring equilibrium solubility,investigating compatibility of each phase and drawing pseudo-ternary phase diagrams.The dapsone microemulsions were evaluated with appearance properties,microscopic morphology,particle size,polydispersity index,viscosity,content,and centrifugal stability.In order to determine the optimal microemulsion formulation,Franz diffusion cell method was used to investigate the in vitro release and in vitro transdermal penetration of dapsone microemulsion.The dapsone microemulsion-based hydrogel（DDS-MBH）was developed based on dapsone microemulsion（DDS-ME）,and the formulation and preparation process were screened and optimized through comprehensive sensory evaluation and in vitro release studies.The quality of dapsone microemulsion-based hydrogel was evaluated with appearance properties,microscopic morphology,pH,viscosity,content,and centrifugal stability.Franz diffusion cell method was used to investigate the in vitro release and in vitro transdermal penetration of dapsone microemulsion-based hydrogel.The skin irritation of dapsone microemulsion-based hydrogel was studied through single and multiple administrations.The preliminary stability of dapsone microemulsion-based hydrogel was investigated through low and high temperature test and 3-month long term test（25±2℃,RH60%±5%）.Results The optimized dapsone microemulsion formulation was:DDS（5.00%w/w）,Triacetin（5.80%w/w）,Labrasol（26.10%w/w）,DGME（26.10%w/w）,H₂O（42.00%w/w）.The Shah method was used to prepare 5%dapsone microemulsion.The appearance of dapsone microemulsion was light yellow clear solution,with average particle size of 55.27 nm,PDI of 0.361,and viscosity of 11～13 mPa·s.The microemulsion droplets under electron microscope were spherical,without drug crystals.In vitro drug release studies showed that the 24 h cumulative drug release rate of dapsone microemulsion was greater than 80%,and in vitro drug release curve conformed to the first-order kinetic equation.In vitro drug transdermal studies showed that the 12 h drug penetration rate（Js）of dapsone microemulsion was 118.90μg/h/cm²,showing good skin permeability.The optimized dapsone microemulsion-based hydrogel formulation was:DDS（5.00%w/w）,Triacetin（5.80%w/w）,Labrasol（26.10%w/w）,DGME（26.10%w/w）,CP-940（1.70%w/w）,H₂O（42.00%w/w）.The appearance of dapsone microemulsion-based hydrogel was light yellow transparent gel,smooth,delicate and easy to spread,pH of5.9～6.0,viscosity of 1200～1300 mPa·s,and content of 48.82～49.17 mg/g.The microemulsion droplets under electron microscope were spherical,and uniformly dispersed in the hydrogel.The 24 h cumulative release rate of dapsone microemulsion-based hydrogel was 78.15%,and in vitro release curve conformed to the first-order kinetic equation and Higuchi equation,showing obvious drug sustained release effect.In vitro drug transdermal studies showed that the 12 h drug penetration rate（Js）of dapsone from microemulsion-based hydrogel was 65.57μg/h/cm²,and the 12 h cumulative skin retention of dapsone was 257.62±33.67μg/cm².Compared with dapsone microemulsion,dapsone microemulsion-based hydrogel increased the skin retention of dapsone,and reduced the transdermal penetration,showing better skin targeting effects.The penetration rate and skin retention of dapsone from microemulsion-based hydrogel were not significantly different from those of marketed dapsone hydrogel（Aczone）.After single and multiple administrations of dapsone microemulsion-based hydrogel,there was no irritation such as erythema and edema on the back skin of rabbits,and the skin morphology was intact and normal.Preliminary stability test showed that the dapsone microemulsion-based hydrogel should be sealed and stored in a dry and cool place to avoid high temperature.Conclusion The results of this study show that the dapsone microemulsion-based hydrogel shows good transdermal permeability and skin retention.The preparation is stable,safe and controllable,which meets the quality requirements of the Chinese Pharmacopoeia gel,having further research value and good application prospects.