Drug Development and Industrial Pharmacy 2013-04-01

In vitro percutaneous absorption enhancement of granisetron by chemical penetration enhancers.

Nanxi Zhao, Dongmei Cun, Wei Li, Xu Ma, Lin Sun, Honglei Xi, Li Li, Liang Fang

文献索引：Drug Dev. Ind. Pharm. 39(4) , 561-8, (2013)

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摘要

Granisetron (GRN), a potent antiemetic agent, is frequently used to prevent nausea and vomiting induced by cancer cytotoxic chemotherapy and radiation therapy.As part of our efforts to further modify the physicochemical properties of this market drug, with the ultimate goal to formulate a better dosage form for GRN, this work was carried out to improve its permeability in vitro.The permeation behavior of GRN in isopropyl myristate (IPM) was investigated across excised rabbit abdominal skin and the enhancing activities of three novel O-acylmenthol derivatives synthesized in our laboratory as well as five well-known chemical enhancers were evaluated.It was found that the steady-state flux of granisetron free base (GRN-B) was about 26-fold higher than that of granisetron hydrochloride (GRN-H). The novel enhancer, 2-isopropyl-5-methylcyclohexyl heptanoate (M-HEP), was observed to provide the most significant enhancement for the absorption of GRN-B. When incorporated in the donor solution with the optimal enhancer M-HEP, the steady-state flux of GRN-B increased from (196.44 ± 12.03) μg·cm⁻²·h⁻¹ to (1044.95 ± 71.99) μg·cm⁻²·h⁻¹ (P < 0.01).These findings indicated that the application of chemical enhancers was an effective approach to increase the percutaneous absorption of GRN in vitro.