IngentaConnect Ester prodrugs of morphine improve transdermal drug delivery: a m...

Authors: Wang, Jhi-Joung¹; Sung, K.C.²; Huang, Jeng-Fen²; Yeh, Chih-Hui³; Fang, Jia-You³

Source: Journal of Pharmacy and Pharmacology, Volume 59, Number 7, July 2007 , pp. 917-925(9)

Abstract:

Two alkyl esters of morphine, morphine propionate (MPR) and morphine enanthate (MEN), were synthesized as potential prodrugs for transdermal delivery. The ester prodrugs could enhance transdermal morphine delivery. The mechanisms of this enhancing effect were elucidated in this study. Both prodrugs were more lipophilic than their parent drug as evaluated by the skin/vehicle partition coefficient (log P) and capacity factor (log K′). The in-vitro skin permeation of morphine and its prodrugs from pH 6 buffer was in the order of MEN > MPR > morphine. MPR and MEN respectively enhanced the transdermal delivery of morphine by 2- and 5-fold. A contrary result was observed when using sesame oil as the vehicle. The prodrugs were stable against chemical hydrolysis in an aqueous solution, but were readily hydrolysed to the parent drug when exposed to skin homogenate and esterase. Approximately 98% MPR and ∼75% MEN were converted to morphine in an in-vitro permeation experiment. The viable epidermis/dermis contributed to a significant resistance to the permeation of ester prodrugs. According to the data of skin permeation across ethanol-, α-terpineol-, and oleic acid-pretreated skin, MEN was predominantly transported via lipid bilayer lamellae in the stratum corneum. The intercellular pathway was not important for either morphine or MPR permeation.

Document Type: Research article

DOI: 10.1211/jpp.59.7.0002

Affiliations: 1: Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan 2: Graduate Institute of Pharmaceutical Science, Chia Nan University of Pharmacy and Science, Tainan Hsien, Taiwan 3: Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan, Taiwan

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$38.34 plus tax Refund Policy

Ester prodrugs of morphine improve transdermal drug delivery: a mechanistic study