In vitro studies on enhancing effect of sodium glycocholate on transbuccal permeation of morphine hydrochloride.
During the perioperative period, gastric emptying rate and first-pass metabolism limit the use of peroral morphine. Buccal mucosa appears to be a potential site for delivery of morphine as it provides direct entry into the system circulation thereby avoiding the hepatic first-pass effect. However, the low permeability of the buccal epithelium results in a low flux of the drug. The use of a penetration enhancer is required to improve the bioavailability of the drug via buccal route. In this study, the enhancing effect of sodium glycocholate (GC) used at 10 mM and 100 mM concentrations on permeation of morphine hydrochloride (MPH) across the porcine buccal mucosa was studied in vitro. Furthermore, in conjunction with its permeation, accumulation of GC in the tissue with time was also studied in order to elucidate the relationship between GC and enhanced mucosal permeation of the drug. Franz diffusion cells were used in the experiments. Permeation of MPH was increased in the presence of 100 mM GC with an enhancement factor of 9.3 whereas no enhancement was obtained with 10 mM GC. The calculated permeability coefficient for MPH in the presence of 100 mM GC was 2.35 x 10(-5) cm/s. Accumulation of GC at 100 mM in the tissue appears to be more significant at 100 mM concentration which correlated well with the increased permeation of the drug. GC was diffused through the buccal epithelium significantly at 100 mM concentration. Interaction of GC with the tissue appears to be more significant at 100 mM concentration compared to 10 mM concentration, thus resulting in a significant enhancing effect.
Senel
S
S
Hacettepe University, Faculty of Pharmacy, Pharmaceutical Technology Department, Ankara, Turkey.
Duchêne
D
D
Hincal
A A
AA
Capan
Y
Y
Ponchel
G
G
D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D000818:Animals; D002610:Cheek; D004058:Diffusion; D004847:Epithelial Cells / Q000378:metabolism; D006000:Glycocholic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D009020:Morphine / Q000493:pharmacokinetics*; D009061:Mouth Mucosa / Q000378:metabolism*; D013552:Swine
D000701:Analgesics, Opioid; D009020:Morphine; D006000:Glycocholic Acid