TY - JOUR
T1 - Enhanced delivery of ketobemidone through porcine buccal mucosa in vitro via more lipophilic ester prodrugs
AU - Hansen, L.B.
AU - Christrup, Lona Louring
AU - Bundgaard, H.
PY - 1992/1/1
Y1 - 1992/1/1
N2 - The in vitro penetration of ketobemidone and various ester prodrugs through porcine buccal mucosa in a modified Ussing chamber was investigated in order to support the selection of a prodrug derivative with optimal buccal absorption. The nine esters studied included carboxylic acid and carbonate esters formed at the phenolic hydroxy group of ketobemidone. The esters were all rapidly hydrolyzed to the parent drug in a porcine buccal epithelial homogenate and only free ketobemidone was detected in the receptor compartment of the Ussing chamber. All the ester prodrugs showed enhanced rates of permeation relative to ketobemidone, the permeability coefficients being 3-30-times higher than that of ketobemidone. The permeability coefficients increased with increasing lipophilicity, expressed in terms of octanol-buffer (pH 7.4) partition coefficients (P), up to log P values of about 1.5 whereupon a plateau or a slight decrease occurred. No toxic effects of ketobemidone or the prodrugs on the buccal membrane were observed as judged from monitoring of the electrical properties of the membrane.
AB - The in vitro penetration of ketobemidone and various ester prodrugs through porcine buccal mucosa in a modified Ussing chamber was investigated in order to support the selection of a prodrug derivative with optimal buccal absorption. The nine esters studied included carboxylic acid and carbonate esters formed at the phenolic hydroxy group of ketobemidone. The esters were all rapidly hydrolyzed to the parent drug in a porcine buccal epithelial homogenate and only free ketobemidone was detected in the receptor compartment of the Ussing chamber. All the ester prodrugs showed enhanced rates of permeation relative to ketobemidone, the permeability coefficients being 3-30-times higher than that of ketobemidone. The permeability coefficients increased with increasing lipophilicity, expressed in terms of octanol-buffer (pH 7.4) partition coefficients (P), up to log P values of about 1.5 whereupon a plateau or a slight decrease occurred. No toxic effects of ketobemidone or the prodrugs on the buccal membrane were observed as judged from monitoring of the electrical properties of the membrane.
UR - http://www.scopus.com/inward/record.url?scp=0026618801&partnerID=8YFLogxK
U2 - 10.1016/0378-5173(92)90321-R
DO - 10.1016/0378-5173(92)90321-R
M3 - Journal article
AN - SCOPUS:0026618801
SN - 0378-5173
VL - 88
SP - 237
EP - 242
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-3
ER -