The Study Of Pheytoin Sodium On Penetration Across The Rat Skin And Gels

Phenytoin sodium (Dilantin sodium, PHS), sodium 5, 5-diphenyl-2, 4- imida- zolidinedione, is an antiepileptic drug. PHS has shown beneficial effects in the treatment of migraine, circumgyration, trigeminal neuralgia, rheumatoidarthritis etc. The dosage forms of PHS authorized on the market are only tablet and injectable preparation. In order to avoid its adverse effect by oral administration and be administrated conveniently and improve patients'compliance, the transdermal administration of PHS is a new idea. Therefore, we studied basic transdermal permeability in great detail and further develops its gels in this paper.Firstly, stability, solubility and oil/water partition coefficient (P) of PHS in different solvents were investigated. The results indicated that PHS is stable under the condition of acid, base, oxidation, light and heat. And the solubility increases with increasing of pH value, wherea P shows the contrary character.Secondly, the transdermal permeability across mouse skin of PHS was studied by using horizontal diffusion cell systemtical. From the penetration kinetics study, it was found that the release of the drug followed zero-rate. The influences of pH on the penetration of PHS were studied and it was shown that with the augment of pH the steady-state flux (Js) increases too, while the permeability coefficient (Ps) decreases, which indicates that it is effective to increase the transdermal absorption of drugs by increasing the pH value. So the suitable pH for the transdermal absorption was ascertained according to the result of experiment. Then, five kinds of penetration enhancers with three different concerntrations were screened by primed method. The experimental results show that five enhancers could improvcd the transdermal delivery of PHS. And the effect is related to the concentration. Under the optimization concentration, the effects of enhancers were as followed: 5%NMP < 5%OA < 5%ME<1%EO <3%Azone. Furthermore, the effects of 3% Azone and 1.0% eucalyptus oil (EO) have no significant difference. But lag time of 3% Azone is much longer and dosage is larger than 1.0% EO. Then, we took next step comparison in the formulations, the enhancement effect of 1.0% EO is the best at last.Finally, we made a research on preparation of PHS gels in terms of different preparation routes and gel supports. The formulation was optimized by mon-factor investigation and orthogonal design method. And we evaluated optimal formulation of PHS gels by appearance, transdermal permeation, prelimitary stability and skin irritation. The result showed that PHS gels have good appearance, content uniformity, accumulative quantity of 614.9283μg.m-2 and PHS gels were permeated at zero rate. And the stability study of PHS gels showed that the drug content, appearance and pH had no obvious changes in acceletated and long-term experiment. The results of skin irritation experiment demonstrated PHS gels hadn't any irritation on rabbit skin.