The Effects Of Penetration Retarder On Percutaneous Delivery Systems

Transdermal and dermal delivery system (TDDS) is an emerging field of pharmaceutical sciences, it is in a front position as new technology and formulations. Transdermal delivery of drug can be used in treatment of systemic diseases and skin localized diseases, because it is more safe, efficient, stable and show better patient compliance than other formulations. For the topical treatment of localized skin diseases, retarder would maximize skin retention and minimize skin penetration due to a better treatment of dermatological disorders and less potential systematic side effect of the applied active agent. The aim of this study was to investigate and optimize the local drug delivery system of skin diseases treatment of azelaic acid (AZA) and metronidazole (MTZ). The retardation effect of diol retarder on the treatment of the topical formulations and the possible mechanistic explanation of the observed retardant effect were proposed. We investigated the physical and chemical properties of drug molecules, established the in vitro high performance liquid chromatography (HPLC) analysis method, studied the method of in vitro percutaneous experiments, determined the type and concentration of retarder and explored the possible mechanism.In this paper, the local administration system of AZA was studied. The degree of ionization of AZA was manipulated by adjusting the pH value of formulations; the results demonstrated that in vitro percutaneous absorption and penetration of AZA was strongly dependent on the ionization state of the drug and the vehicle of the formulations. In this study, the skin retention and therapeutic efficiency increased markedly for the solubilized form, which showed the superiority over the formulation of Finacea?. The presence of retarder 1, 4-cyclohexanediol in the solubilized formulations significantly reduced the flux of applied AZA without reducing the retention of AZA in dermatological relevant epidermal layer. The application of this retarder in the suspended formulations of AZA has no significant retardant effect, which indicated that the mechanism may be associated with the skin structure.This paper also researched and optimized local drug delivery system of MTZ, established the in vitro analysis method and its physical and chemical properties. It was demonstrated that the ratio of retardation effect decreased form 50% to 20% (w/w) if reduced the concentration of 1, 2-hexanediol, which was another component of the formulations. Moreover, there was no retardation effect of the formulation that only contained 1, 4-cyclohexanediol compared to the control. It was found that a combination of 1, 2-hexanediol and 1, 4-cyclohexanediol has shown a synergistic retardation effect on percutaneous absorption of MTZ.Furthermore, the study was also carried out to shine a light on mechanistic aspect of the retardation effect. For the synergistic retarder, all of the formation of hydrogen bond between stratum corneum and the retarder, the hydroxyl position, the number and carbon chain length of 1, 2-hexanediol, ring structure of 1, 4-cyclohexanediol were the key factors. Elucidation of the retardation mechanism would help us to provide an important theoretical basis and discover novel penetration retardants.