title: 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).
  
  
  CONCLUSIONS
  These findings indicated that the application of chemical enhancers was an effective approach to increase the percutaneous absorption of GRN in vitro.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
authors.forename: Nanxi
authors.initials: N
authors.lastname: Zhao
authors.forename: Dongmei
authors.initials: D
authors.lastname: Cun
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.forename: Honglei
authors.initials: H
authors.lastname: Xi
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000932:Antiemetics / Q000737:chemistry / Q000493:pharmacokinetics*; D017829:Granisetron / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D009226:Myristates / Q000737:chemistry*; D010539:Permeability / Q000187:drug effects; D011817:Rabbits; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
chemical_list: D000932:Antiemetics; D017829:Granisetron; D009226:Myristates; C008205:isopropyl myristate