In vitro percutaneous absorption enhancement of granisetron by chemical penetration enhancers

Abstract

Granisetron (GRN), a potent antiemetic agent, is frequently used to prevent nausea and vomiting induced by cancer cytotoxic chemotherapy and radiation therapy.

Objective: 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.

Methods: 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.

Results: 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).

Conclusion: These findings indicated that the application of chemical enhancers was an effective approach to increase the percutaneous absorption of GRN in vitro.

Keywords::

• Granisetron
• transdermal
• 2-isopropyl-5-methylcyclohexyl heptanoate
• penetration enhancer
• in vitro