The molecular weight dependence of nasal absorption: the effect of absorption enhancers.
A series of polyethylene glycols (PEGs) ranging in molecular weight from near 600 to over 2000 daltons was used to study the effects of three absorption enhancers (sodium glycocholate, sodium lauryl sulfate, and polyoxyethylene 9 lauryl ether) on the molecular weight permeability profile of the nasal mucosa of the rat. Molecular weight-permeability properties were studied both by following changes in the excretion of the polyethylene glycols as a function of their molecular size and by examining the nasal mucosa for morphologic changes following exposure to the PEG/enhancer mixtures. Each absorption enhancer was found to affect the mucosa and its permeability in a unique manner. At a 1% concentration, sodium glycocholate only slightly affects tissue morphology and does not significantly alter the molecular weight permeability profile of the mucosa. In contrast, 1% sodium lauryl sulfate causes severe alteration of the mucosa and also greatly increases the absorption of both the PEG 600 and the PEG 2000 oligomers. Polyoxyethylene 9 lauryl ether was found to exert its action in a concentration-dependent manner. At a concentration of 0.1%, few changes were seen in either mucosal integrity or permeability. At a 1% concentration, however, a significant alteration in the structure of the mucosal tissues as well as a profound increase in the permeability of the mucosa to the PEGs was observed. Correlation of mucosal integrity with the effectiveness of an enhancer indicates that some of these compounds appear to be acting by altering the structure of the mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
Donovan
M D
MD
College of Pharmacy, University of Michigan, Ann Arbor 48109.
Flynn
G L
GL
Amidon
G L
GL
D000042:Absorption / Q000187:drug effects; D000818:Animals; D006000:Glycocholic Acid / Q000494:pharmacology; D008297:Male; D008970:Molecular Weight; D009297:Nasal Mucosa / Q000378:metabolism*; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology
D000077423:Polidocanol; D012967:Sodium Dodecyl Sulfate; D011092:Polyethylene Glycols; D006000:Glycocholic Acid