Percutaneous absorption of metopimazine and effect of cyclodextrins.
Metopimazine (MPZ) is used to prevent emesis during chemotherapies. A transdermal delivery system of MPZ may present a great advantage in patients to improve compliance. Hydroxypropyl beta cyclodextrin (HPbetaCD) and partially methylated beta cyclodextrin (PMbetaCD) were tested to enhance the percutaneous absorption of MPZ through pig skin using Franz's cells. The MPZ hydrochloride flux was low with 0.176 +/- 0.054 microg/h/cm(2) and no flux was detected with a suspension of MPZ (base). The used characterization analyses demonstrated the formation of an inclusion complex with cyclodextrin and this complex improved percutaneous absorption of MPZ. Flux was increased to 0.240 +/- 0.032 microg/h/cm(2) and 0.566 +/- 0.057 mug/h/cm(2) for HPbetaCD and PMbetaCD, respectively, with a concentration of 20%. This study has shown that HPbetaCD and PMbetaCD improved the percutaneous penetration of MPZ. Cyclodextrin complexes increased MPZ bioavailability at the skin surface and PMbetaCD was also able to extract cutaneous fatty acids.
Frédéric
Bounoure
B
Laboratoire de Pharmacie, UFR Medecine Pharmacie, IFR (Institute for Biomedical Research), Universite de Rouen, Rouen, Cedex, France.
Malika
Lahiani-Skiba
LS
Marie
Hubert
H
Eric
Mallet
M
Philippe
Arnaud
A
Mohamed
Skiba
S
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology; D000279:Administration, Cutaneous; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D004431:Ear, External; D066298:In Vitro Techniques; D007540:Isonipecotic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010539:Permeability; D012869:Skin Absorption; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013552:Swine; D047392:beta-Cyclodextrins / Q000494:pharmacology
D000277:Adjuvants, Pharmaceutic; D000932:Antiemetics; D007540:Isonipecotic Acids; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C005260:metopimazine