Feasibility of transdermal delivery of prochlorperazine.
Prochlorperazine (PCPZ) is used as a drug of first choice to treat opioid-induced nausea and vomiting. To examine the feasibility of the development of a transdermal drug delivery system for PCPZ, we performed an in vitro skin permeation study with hairless mouse skin. When the concentration of L-menthol in the hydrogel was 0-0.5%, the PCPZ flux was small; on the other hand, the flux was increased remarkably when the L-menthol concentration was higher than 1%. The optimal formulation of hydrogel would be contained 20% isopropanol (IPA), 10% N-methyl-2-pyrrolidone (NMP), 2% L-menthol and 1% PCPZ. The strong inhibitory effects to stereotyped behavior were observed at 4 h after administration of PCPZ hydrogel, and the efficacy was sustained for at least 8 h after the administration in mice in vivo. Thus, it was considered that PCPZ was delivered to brain via systemic circulation by the administration of PCPZ hydrogel.
Obata
Yasuko
Y
Department of Pharmaceutics, Hoshi University, Tokyo, Japan. obata@hoshi.ac.jp
Otake
Yuki
Y
Takayama
Kozo
K
D000279:Administration, Cutaneous; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems / Q000379:methods*; D005240:Feasibility Studies; D020100:Hydrogels; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability; D011346:Prochlorperazine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects
D000932:Antiemetics; D020100:Hydrogels; D001058:Apomorphine; D011346:Prochlorperazine