The Effect Of Penetration Enhancers On The Permeability Of Drugs Through Buccal Mucosa

With the development of modern pharmaceutical technology,non-oral drug delivery systems have developed rapidly.Mucosal drug delivery system for systemic therapy has become an important means of treating diseases,such as buccal mucosal drug delivery system.Buccal mucosal drug delivery has many advantages: administration easily,high patient acceptance and compliance;self-reparation strongly, low enzyme activity,avoiding gastrointestinal enzymes,acid degradation and liver first-pass effect.However,some drugs are difficult to penetrate through mucosa or slow penetration rate in practical applications,so it is necessary to increase the penetration rate and quantity of drugs by using penetration enhancers.In order to study the effect of penetration enhancer on the penetration of drugs through buccal mucosa,we studied in both penetration enhancers and drugs.The porcine buccal mucosa was used as model mucosa which is similar with human buccal mucosa in morphology,penetration barriers and composition of lipids.The model drugs were hydrocortisone,caffeine and benzoic acid which are large differences in physico-chemical property,such as molecular weight and oil/water partition coefficients.The penetration enhancers were Azone^?,menthol and oleic acid. The experiment equipment was TK-12B transdermal diffusion instrument.The high performance liquid chromatography(HPLC) analysis methods were established to assay the dissolvability in water at 37℃and the concentration of drugs via porcine buccal mucosa at each time point.The results showed that the methods were suitable for the drugs,and the verifications were consistent with requirements.The following conclusions can be obtained from the study that penetration enhancers worked on the permeability of model drugs through porcine buccal mucosa. Firstly,Azone^?,menthol and oleic acid can enhance the permeability of hydrocortisone markedly,but have little enhancement on caffeine.Oleic acid enhanced the permeability of benzoic acid largely,while Azone^? and menthol almost have no enhancement.It indicated that the relationship between enhancement of enhancers and the physico-chemical property of drugs is very important and interesting,and the drugs with larger molecular volume and higher oil/water partition can be better enhanced by the enhancers.Secondly,Using mixed enhancers also has markedly enhancing effects on hydrocortisone,while it is not better than single enhancers.So there is no synergistic action among the three enhancers.Thirdly,the enhancement of oleic acid on hydrocortisone is better than Azone^? and menthol. Fourthly,the menthol as enhancer,the permeability of hydrocortisone through porcine buccal mucosa increased much more than that of caffeine,while the permeability of hydrocortisone through mile hairless mice skin was much worse than caffeine.So the enhancing mechanism of menthol that worked on baccal mucosa is very different from that on skins.The results is important in the further mechanism studied of Azone^?,menthol and oleic acid,and also is sense to instruction the development of oral mucosa drug delivery system.