| Shaoyao-Gancao-Tang (SGT) composed of Paeoniae (Shaoyao) and Glycyrrhizae (Gancao) radices takes its source at Zhang Zhongjing "Treatise on Febrile Diseases". SGT administrated orally can relieve a cough and asthma, and it is also effective in uterine smooth muscle, gastrointestinal tract, antipyretic- analgesic, anti-inflammatory as well as two-ways regulation. However, the therapeutic use of SGT is limited by gastrointestinal irritation, low bioavailability and Pseudo-aldosterone disease. Transdermal delivery offers an alternative route for administering SGT that bypasses the gut and improves the bioavailability of SGT. Furthermore, by transdermal delivery system drug can achieve deep local targeting of subcutaneous tissue and not only exert their peripheral neural inhibition and local direct action, but also exert systemic action when the drug penetrates into subcutaneous capillaries then into the blood circulation. For SGT, transdermal delivery has more advantages than administrating orally.This paper adopts two compounds Peoniflorin and Glycyrrhetinic acid to determine the penetration parameters in vitro. Peoniflorin is active ingredient of Paeoniae and Glycyrrhetinic acid is a metabolite of Glycyrrhizic acid, a major active ingredient of Glycyrrhizae. The diffusion coefficients of Peoniflorin of viable and intact skin are 5.66x10-7 and 7.51x10-8, respectively. Peoniflorin has a high solubility in water, which leads to the high concentration of Peoniflorin (6.56x104μg/cm3) on the surface of skin. Peoniflorin can penetrate through skin easily in the water without any chemical enhancers. However, the concentration of Glycyrrhetinic acid on the surface of skin is as low as 572.71μg/cm3. The partition coefficient between stratum corneum and viable skin is 9.6, which shows that Glycyrrhetinic acid is a compound with strong lipophilicity. Thus not only stratum corneum, but viable skin also acts as a barrier to the penetration of Glycyrrhetinic acid. In this paper, non-aqueous solvent system and organic base are used to improve penetration of Glycyrrhetinic acid. Isopropyl myristate (IPM)-alcohol system significantly increase the solubility of Glycyrrhetinic acid. For instance the solubility of Glycyrrhetinic acid is from 30.91μg/ml to 4.85 mg/ml in IPM-ethanol system without organic base. After organic base added, the solubility increases only a little, but organic base can decrease the apparent log P. The apparent logP is 1.62 for triethylamine-Glycyrrhetinic acid. Thus, it improves the partition of Glycyrrhetinic acid into viable skin and reduce the barrier of skin to increased penetration. In order to further confirm the mechanism by which the organic bases enhanced the penetration of Glycyrrhetinic acid, conductivity measurement,1H NMR spectroscopy and FT-IR analysis are used to observe the formation of ion pair between Glycyrrhetinic acid and organic base. The percentage of ethanol in the IPM-ethanol system is altered and in the presence of organic base, the addition of ethanol increases the solubility of Glycyrrhetinic acid in a concentration dependent manner. Increases in cumulative amount permeated within 24 h reaches a maximum at around 5% ethanol, which shows cumulative amount permeated largely depends on the concentration and activity of Glycyrrhetinic acid-organic base ion pair. On the basis of the original system, ointments with compounds are prepared and the influence between the penetration of Peoniflorin and Glycyrrhetinic acid is studied. Peoniflorin enhances the penetration of Glycyrrhetinic acid markedly. After Peoniflorin added, the cumulative amount permeated of Glycyrrhetinic acid increases 1.7 fold. But Glycyrrhetinic acid has no effect on Peoniflorin.
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