Study Of Buprenorphine Hydrochloride Gel Transdermal Delivery System

Objective Although transdermal delivery of narcotic analgesics had been investigated deeply in recent years, the study of buprenorphine hydrochloride gel had not been mentioned.The aim of this study is:l) to investigate the cutaneous permeation of buprenorphine hydrochloride gel through hairless mouse skin and the effect of permeation enhancers on this transdermal drug delivery system;2)to evaluate the pharmacodynamics of BHG on rat;3)to evaluate the skin irritation and sensitization of BHG on rabit. MethodsParti : Stage 1 (choice of gel matrix),the study was divided into groupA(2%carbopol940),groupB(4%carbopol940),groupC(6%carbopol940), and groupD (polyethylene glycol), in which the concentration of BH were 1.0%.Diffusion studies across hairless mouse skin were performed using improved Franz diffusion cell.Concentration of BH in the receptor was essayed by HPLC and the permeation parameters such as Js and ER were evaluated.Stage2(choice of permeation enhancers),diffusion studies were divided into no permeation enhancers group, in which the concentration of buprenorphine hydrochloride were 0.5%, 1.0% (control) or 2.0%, and permeation enhancers group, in which including oleic group (2%, 4%, 6%), azone group (1%, 2%, 4%) and mixed group (4%oleic+4%a/.one). Alsojs and ER were evaluated. Part2: Twelve rats were randomly allocated into study group and controlgroup,six in each group.After treated with BHG, benzoquinone were injected in abdomen in 2,6,12,24,48hours.After injection, 10 scores were criticized every 5 minutes with double blind method.These 10 scores were added to present the pain degree.Higher score more pain.Part3: Six rabbits were shaving in both side on their back about 3cm X 3cm. The skin irritation index was calculated according to scores using FHSA method.Results Parti : Stage 1,there was significant difference between groups ( P<0.05 ) .Group B had the highest Js().Stage2,Js in no permeation enhancers group were (0.694:0.11), (0.90+0.14) and (1.18+0.10) ug/cm2-h respectively, among which there was no significant differences (P>0.05). Mixed group provided the maximum permeation. Corresponding values of Js and ER were (13.22+1.27) ng/cm2-h and 14.6.Part2: Scores between two groups had significant difference(PO.05).Scores of study group was lower than that of control group.Part3: Original irritation index was 2.3,which indicated the irritation of BHG was medium-grade.Conclusions Permeation enhancers evidently increase Js of buprenorphine hydrochloride and made the release kinetics of gel changed from one-order to near zero-order.BHG had curative analgesia effect when used on mouse.The irritation of BHG on rabbit skin was medium-grade.