Enhanced ex vivo buccal transport of propranolol: evaluation of phospholipids as permeation enhancers.
The aim of the present study was to evaluate the effects of two phospholipid permeation enhancers, lysophosphatidylcholine (LPC) and didecanoylphosphatidylcholine (DDPC), along with a fusidic acid derivative, sodium taurodihydrofusidate (STDHF) and ethanol (EtOH) on the buccal transport of propranolol hydrochloride (PPL) using an ex vivo buccal diffusion model. The permeation rate of [3H]PPL as measured by steady-state fluxes increased with increasing EtOH concentration. A significant flux enhancement (P<0.05) was achieved by EtOH at 20 and 30 %v/v concentrations. At a 0.5 %w/v permeation enhancer concentration, the buccal permeation of [3H]PPL was significantly enhanced by all the enhancers studied (i.e., LPC, DDPC and STDHF) compared to the control (phosphate-buffered saline pH 7.4, PBS). LPC and DDPC displayed a greater degree of permeation enhancement compared with STDHF and EtOH-PBS mixtures with an enhancement ratio of 3.2 and 2.9 for LPC and DDPC, respectively compared with 2.0 and 1.5 for STDHF and EtOH:PBS 30:70 %v/v mixture, respectively. There was no significant difference between LPC and DDPC for the flux values and apparent permeability coefficients of [3H]PPL. These results suggest that phospholipids are suitable as permeation enhancers for the buccal delivery of drugs.
Lee
Jaehwi
J
Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, IN 47907-2091, USA. JL@akinainc.com
Choi
Young Wook
YW
D000042:Absorption; D000278:Administration, Buccal; D000818:Animals; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology; D005672:Fusidic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability; D010713:Phosphatidylcholines / Q000494:pharmacology*; D011433:Propranolol / Q000493:pharmacokinetics*; D013552:Swine
D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; C480658:didecanoylphosphatidylcholine; D000431:Ethanol; D005672:Fusidic Acid; D011433:Propranolol