Development and in vivo assessment of a transdermal system for physostigmine.
A copolymer was developed as a transdermal (TD) system for physostigmine. The loading was carried out with a solution of physostigmine (PHY) base (20 mg/ml) in water/ethanol: 80/20 (v/v) at 40 degrees C for 3 h. The PHY load was 5.3 mg/cm2 (n = 3). Desorption carried out in vitro showed that 70% was desorbed during the first 6 h. More than 50% of the PHY was degraded within 45 min in skin homogenate. The TD was tested in vivo in rabbits during a 24 h experiment. PHY was quantified using a validated HPLC method. AUC0-24 h was 245.2 +/- 337.2 h.ng/ml. The mean pad flux reached 4.6 +/- 6.3 micrograms/cm2 from 0 to 24 h and, 24 h after the application of the pad, 110 micrograms/cm2 of PHY had been passed through the skin. After removed of the patch, plasma concentrations first increased from 15.8 +/- 28.6 ng/ml (at 24 h) to 21.4 +/- 36.7 ng/ml, then decreased with an elimination half-life of 0.7 +/- 0.2 h. AChE inhibition percentages increased from 6.5 +/- 2.3% to 16.0 +/- 27.7%. In vitro and in vivo studies in rabbit have shown that this system is suitable for further investigations in order to obtain a possible carrier for PHY therapy.
Benech
H
H
CEA, Service de Pharmacologie et d'Immunolgie, DSV/DRM, CEA/Saclay, Gif sur Yvette, France. benech@dsvidf.cea.fr
Vincenti
M
M
Fouchart
F
F
Pruvost
A
A
Vienet
R
R
Istin
M
M
Grognet
J M
JM
D000287:Administration, Topical; D000818:Animals; D019540:Area Under Curve; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D006207:Half-Life; D008297:Male; D010830:Physostigmine / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D011817:Rabbits; D012867:Skin / Q000378:metabolism*
D002800:Cholinesterase Inhibitors; D010830:Physostigmine