| Danazol,a synthetic derivative of 17 a -ethinyltestosterone,is effective in the treatment of endometriosis. Danazol is widely used as an oral remedy,which causes many side effects,mainly results liver dysfunction. Recently,some studies suggest that vaginal administration can serve as an alternative route for danazol therapy that might produce fewer and less severe side effects. Therefore,we prepared a vaginal pellicle of danozol.In this study,polyvinyl alcohol (PVA)0486 and hydroxy-propyl methyl cellulose (HPMC) E50 were considered for administering danazol and prepared using a general casting method.In an effort to enhance the permeation rate of danazol,three methods including the use of penetration enhancers the increase of the drug load of the system,the use of various polyvinyl alcohol,have been studied. The in vitro rabbit vaginal mucosa permeation tests from each pellicle were carried out by Valia-Chien diffusion cell consisting of two compartments and high performance liquid chromatography (HPLC) method. The results showed that the permeation rate of danazol was enhanced by Az. The permeation effect of Az didn't increased with increase of Az concentration. In this study,the best concentration is 6.24%w/v,which caused the best permeation effect,with a 1.7 fold enhancement.Danazol concentration in the pellicles has also found to have an effect on the permeation. The rabbii vaginal mucosa permeation rate was increased from 3.59+0.13 u g cm-2 h-1 to 4.88 + 0.16 u g cm-2 h-1 as danazol concentration from 3.46%w/v to 17.39%w/w and did not change as the increase of concentration from 17.37%w/w to 27.87%w/w. Various pellicles of PVA:HPMC were found to provide similar rabbit vaginal mucosa permeation (P>0.05).The in vitro release tests from each pellicle were evaluated using dissolutionmedium and stirring rate. It was found that quality control could achieve when using phosphate buffer of 40 %v/v polyethylene glycol 400 with 20%v/v isopropyl alcohol (pH=5) as dissolution medium and 50rmp stirring rate. Using this dissolution medium and this stirring rate,the in vitro release tests various PVA:HPMC pellicles and various danazol concentrations were studied. The results showed that all release profiles followed Higuchi equation. The release rate using PVA as ingredient of pellicle was obvious lower than that of using PVA.-HPMC (2:1) and PVA:HPMC(1:1). The release rate of danazol was affected by drug concentration in PVA:HPMC (1:1) pellicle. The release rate increased as the increased of concentration from 8.70%w/w,17.39%w/w to 27.87%w/w.According to research results above,danazol vaginal pellicle composed of danazol 3.12mg cm-2,Az 1.12 mg cm-2,PVA0486 4.37 mg cm-2;HPMC4.37 mg cm-2 and glycerol 4.96 mg cm-2 was used in in vivo rabbit studies,which compare with orally. The concentrations in plasma and uterus of danazol in rabbit administrated vaginally or orally have been determined by HPLC methods. The oral dosage was 12 mg kg-1,and the vaginal dosage was 3 mg kg" . The results showed that the concentration of serum treated vaginally were much lower than those of 4-fold danazol amount treated orally,but the uterine tissue concentrations of danazol treated former were higher than those of the latter. To be compared with oral administration,it is expectable that the pellicles administrated through vagina have equal theraputic effects but lower side effects. |
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