Study On Penetration Rate Of Drug Via Different Skins

Benzoic acid, caffeine and hydrocortisone are usually used in the study on transdermal drug delivery systems. Benzoic acid, whose molecular weight is 122.1, is a white, crystalline organic compound. It is melting at 121~124. 5℃;slightly soluble in water, the solution is acidic, soluble in ethanol. It is used as an antifungal agent, and has good antifungal activity to pathogenetic fungi, usually used in various compound preparation for external use together with salicylic acid;Caffeine, whose molecular weight is 194.2, is a purine alkaloid extracted from tea and coffee. It is melting at 235~238℃, is diffluent in hot water, slightly soluble in water, the solution is basic , if used properly caffeine can dispel tiredness and stimulant nervous, it is the stimulant of central nervous system and has positive effect on cardiovascular system. Moreover, it is able to promote secretion of gastric acid and alleviate migraine. It also plays the wide-ranging roles in the other systems of the body;hydrocortisone, whose molecular weight is 362.5, is one kind of glucocorticoids secreted by adrenal gland. It is melting at 212~222℃, insoluble in water;slightly soluble in ethanol. Its mainly function is influence the synthesize and metabolize of glucide, protein and fat. It can prevent or restrain fever, rubefaction, tumefactionand tenderness induced by local inflammation for exteral use, and can be absorbed percutaneous, especially in the scathing skin, is usually used to cure allergic dermatitis, eczema;neurodermatitis , seborrheic dermatitis, itching and so on.The test substances were chosen on the basis of their range in physico-chemical properties and their recommendation as reference compounds by the OECD, they were also widely used in the study on transdermal drug delivery systems. We mainly studied the in vitro percutaneous penetration rate via human skin, rabbit skin and mouse skin of the three kinds of drug in this article. The main contain are: 1.The studybefore the in vitro skin permeation tests, i.e., the ultraviolet spectrum and high performance liquid chromatography (HPLC) methods for the assay of benzoic acid, caffeine and hydrocortisone were established firstly and then the physicochemical properties, especially the drug solubility in various solvent systems such as water(37°C), water contain 20% ethanol were examined;to established the experiment condition and process in vitro skin percutaneous permeation study of the three drug. 2. The in vitro skin permeation tests of the three drug via three different skins;i.e., respectively tested the percutaneous penetration rate of saturated solution of each drug via the three different skins, during the test of benzoic acid and caffeine, the receptor medium was the sodium chloride solution(0.9%);as hydrocortisone is insoluble in water, we used the the sodium chloride solution(0.9%) contain 20% ethanol to be its receptor medium. Moreever, we studied the quantitative structure-activity relationships of branched-chain alkanols as skin permeation enhancers, we established the correlation equations between enhancement potencies and the physico-chemical parameters relevant to lipophilicity and position of hydroxyl group for 16 alkanols using the stepwise multiple linear regression analysis.The experiment results showed that the penetration coefficient of benzoic through mouse skins rabbit skuK human skin was 1.37xlO"5cm-s"\ 9.02x10"6 cm s"1 and "1, respectively, Px: Pβ: Pa**!: 1.3: 0.8;the penetration coefficent ofcaffeine through mouse skku rabbit skm> human skin was 4.34x10'cm-s' > 9.74xlO"7cms"1 and 8.42X10'8 cms"1, respectively, Pα: Pa: P*=l: 5.2: 11.6. The penetration coefficent of hydrocortisone through mouse skin^ rabbit skin> human skin was l.OSxlO^cm-s"^ S.OSxlO^cm-s"1 and 3.53xlO"8 cm-s"1, respectively, P a: P a: P a=1: 29.2: 86.4.These results showed that, the pentration rate of drug penetrate through different skins exist discrepancy, and for different drugs, the pentration rate discrepancy is obviously differ. Among the three drug, the pentration rate discrepancy of benzoic through three skins is lesser, the pentration rate discrepancy of caffeine through three skins isrelatively biggish, the pentration rate discrepancy of hydrocortisone obviously.When the solubility of drug is properly and the molecular weight is small, the pentration coefficient discrepancy between human skin and mouse skin or rabbit skin are indistinctive, if the solubility of drug is too big or too small, and the molecular weight is biggish, the pentration coefficient through human skin is distinctively smaller than mouse skin and rabbit skin, therefore, for such drugs, we couldn't simply estimate their penetration ability through human skin from the skin permeation experiment data obtained from mouse skin or rabbit skin.The results of the study on the quantitative structure-activity relationships of alkanols permeation enhancers revealed that: the enhancement potencies of alkanols are excellently correlated with their lipophilicity and position of hydroxyl group. The enhancement potency of an alkanol will increase when it has greater lipophilicity but decrease as the hydroxyl group moves from the end of the chain towards the center of the enhancer alkyl chain. The conclusion can not only instruct the desigh and selection of alkanols permeation enhancers directly, but also the desigh and selection of the other enhancers whose enhancement mechanism is similar as alkanols. The predict parameters used in the mathematic matrix we established can be easily obtained by calculation, so it is not necessary to be tested by fussy experiment, is convenient and useful in predicting the enhancement potencies of alkanols.