TY - JOUR

T1 - TR146 cells grown on filters as a model of human buccal epithelium

T2 - IV. Permeability of water, mannitol, testosterone and beta-adrenoceptor antagonists. Comparison to human, monkey and porcine buccal mucosa

AU - Nielsen, H M

AU - Rassing, M R

AU - Nielsen, Hanne Mørck

PY - 2000

Y1 - 2000

N2 - The objective of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium. For this purpose, the permeability of water, mannitol and testosterone across the TR146 cell culture model was compared to the permeability across human, monkey and porcine buccal mucosa. Further, the permeability rates of ten beta-adrenoceptor antagonists (acebutolol, alprenolol, atenolol, labetalol, metoprolol, oxprenolol, pindolol, propranolol, timolol and tertatolol) across the TR146 cell culture model and porcine buccal mucosa were related to their lipophilicity (logD(oct; 7.4)) and capacity factor (k') and to their polar water accessible surface area (PWASA). For water, mannitol, testosterone and some of the beta-adrenoceptor antagonists, the permeability enhancement across the TR146 cell culture model in the presence of sodium glycocholate (GC) was determined. The mannitol and testosterone permeability across the TR146 cell culture model could be related to the permeability across porcine and human buccal mucosa. The permeability of the beta-adrenoceptor antagonists across the TR146 cell culture model varied between 2.2 x 10(-6) cm/s (atenolol) and 165 x 10(-6) cm/s (metoprolol). For propranolol the cellular permeability value (P(c)) was lower than expected, probably due to accumulation in the TR146 cell layers. Limited correlation of permeability with k' was observed both for the TR146 cell culture model and the porcine buccal mucosa, although the porcine permeability values were approximately 100 times less than the values determined with the TR146 cell culture model. The permeability values were also found to decrease with increasing PWASA. The PWASA value seemed to be more predictable for permeability than k'. The presence of 12.5 mM GC increased the permeability only for the hydrophilic atenolol, which may help explain the mechanism for GC-induced enhancement. The present results indicate that the TR146 cell culture model can be used as an in vitro model for permeability studies and mechanistic studies of human buccal drug delivery of drugs with different lipophilicity.

AB - The objective of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium. For this purpose, the permeability of water, mannitol and testosterone across the TR146 cell culture model was compared to the permeability across human, monkey and porcine buccal mucosa. Further, the permeability rates of ten beta-adrenoceptor antagonists (acebutolol, alprenolol, atenolol, labetalol, metoprolol, oxprenolol, pindolol, propranolol, timolol and tertatolol) across the TR146 cell culture model and porcine buccal mucosa were related to their lipophilicity (logD(oct; 7.4)) and capacity factor (k') and to their polar water accessible surface area (PWASA). For water, mannitol, testosterone and some of the beta-adrenoceptor antagonists, the permeability enhancement across the TR146 cell culture model in the presence of sodium glycocholate (GC) was determined. The mannitol and testosterone permeability across the TR146 cell culture model could be related to the permeability across porcine and human buccal mucosa. The permeability of the beta-adrenoceptor antagonists across the TR146 cell culture model varied between 2.2 x 10(-6) cm/s (atenolol) and 165 x 10(-6) cm/s (metoprolol). For propranolol the cellular permeability value (P(c)) was lower than expected, probably due to accumulation in the TR146 cell layers. Limited correlation of permeability with k' was observed both for the TR146 cell culture model and the porcine buccal mucosa, although the porcine permeability values were approximately 100 times less than the values determined with the TR146 cell culture model. The permeability values were also found to decrease with increasing PWASA. The PWASA value seemed to be more predictable for permeability than k'. The presence of 12.5 mM GC increased the permeability only for the hydrophilic atenolol, which may help explain the mechanism for GC-induced enhancement. The present results indicate that the TR146 cell culture model can be used as an in vitro model for permeability studies and mechanistic studies of human buccal drug delivery of drugs with different lipophilicity.

KW - Adrenergic beta-Antagonists

KW - Animals

KW - Cells, Cultured

KW - Cheek

KW - Glycocholic Acid

KW - Humans

KW - Macaca fascicularis

KW - Mannitol

KW - Mouth Mucosa

KW - Permeability

KW - Solubility

KW - Species Specificity

KW - Swine

KW - Testosterone

KW - Water

M3 - Journal article

C2 - 10692640

VL - 194

SP - 155

EP - 167

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 2

ER -