Development and biopharmaceutical evaluation of quinupramine-EVA matrix containing penetration enhancer for the enhanced transdermal absorption in rats.
To increase the skin permeation of quinupramine through the rat skin, different types of enhancers were added to an ethylene-vinyl acetate (EVA) matrix containing 2% quinupramine. The effects of the enhancers on the level of quinupramine permeation through the skin were evaluated by using Franz diffusion cells that were fitted with the intact excised rat skin. Among the enhancers used, which included fatty acids (saturated and unsaturated), glycerides, pyrrolidones, and nonionic surfactants, polyoxyethylene-2-oleyl ether showed the best enhancement. The pharmacokinetics and bioavailability of quinupramine from an EVA matrix were examined to determine the level of percutaneous absorption in rats. The percutaneous absorption of quinupramine from the EVA matrix with or without an enhancer was investigated. Quinupramine was administered orally or intravenously to compare the pharmacokinetic parameters with that of the transdermal route. The relative bioavailability of quinupramine in the matrix containing polyoxyethylene-2-oleyl ether as an enhancer was approximately 2.81 times higher than the group without an enhancer. Histological examination revealed that the skin pretreated with the EVA matrix containing the enhancers had a loosely layered stratum corneum. These results show that the quinupramine-EVA matrix containing a permeation enhancer could be a good transdermal delivery system for providing sustained plasma concentrations.
Shin
Sang-Chul
SC
College of Pharmacy, Chonnam National University, Gwangju, Korea.
Kim
Jin
J
Kim
Woong-Jang
WJ
Kim
Seong-Jin
SJ
Cho
Cheong-Weon
CW
D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000279:Administration, Cutaneous; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002210:Caprylates / Q000494:pharmacology; D003692:Delayed-Action Preparations; D003984:Dibenzazepines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D005227:Fatty Acids / Q000494:pharmacology; D005989:Glycerides / Q000494:pharmacology; D006018:Glycols / Q000494:pharmacology; D019787:Linoleic Acid / Q000494:pharmacology; D008297:Male; D010938:Plant Oils / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011145:Polyvinyls / Q000737:chemistry*; D011760:Pyrrolidinones / Q000494:pharmacology; D011812:Quinuclidines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013501:Surface-Active Agents / Q000494:pharmacology
D000277:Adjuvants, Pharmaceutic; D000929:Antidepressive Agents, Tricyclic; D002210:Caprylates; D003692:Delayed-Action Preparations; D003984:Dibenzazepines; D005227:Fatty Acids; D005989:Glycerides; D006018:Glycols; D010938:Plant Oils; D011145:Polyvinyls; D011760:Pyrrolidinones; D011812:Quinuclidines; D013501:Surface-Active Agents; C016438:ethylenevinylacetate copolymer; C028338:quinupramine; D011092:Polyethylene Glycols; C033084:polyethylene glycol oleyl ether; D019787:Linoleic Acid