Effect of beta-cyclodextrin on the in vitro permeation rate and in vivo rectal absorption of acetaminophen hydrogel preparations.
The amounts of beta-cyclodextrin and hydroxyl propyl methyl cellulose (HPMC) affecting the in vitro permeation rate of acetaminophen containing in both aqueous solutions and HPMC hydrogel preparations through the dialyzer tubing and isolated rat rectum were investigated. The partition coefficient of acetaminophen with or without beta-cyclodextrin in water/n-octanol system was also studied. In vivo absorption experiments of these test formulations were carried out by rectal administration in rats. The results indicate that the concentrations of beta-cyclodextrin and HPMC used decreased the amount permeated of acetaminophen from both test formulations. The more the amount of beta-cyclodextrin or HPMC the slower the permeation rate of acetaminophen. The permeation rate of acetaminophen through the dialyzer tubing was higher than that of acetaminophen through the isolated rat rectum. The result also shows beta-cyclodextrin and HPMC markedly reduced the in vivo bioavailability of acetaminophen from both test formulations. The lower partition coefficient and the higher hydrophilic properties of beta-cyclodextrin inclusion complex, and the higher viscosity of HPMC hydrogel matrix might be responsible for decreasing the in vitro permeation rate and depression of in vivo rectal absorption of acetaminophen. The in vitro permeation data was well correlated with in vivo absorption results, suggesting that the in vitro permeation study regardless of the dialyzer tubing method or the isolated rat rectum method might be used to estimate the in vivo rectal absorption of acetaminophen.
Lin
S Y
SY
Department of Medical Research, Veterans General Hospital-Taipei, Republic of China.
Yang
J C
JC
D000082:Acetaminophen / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D003505:Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*; D004058:Diffusion; D065347:Hypromellose Derivatives; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains; D012007:Rectum / Q000378:metabolism; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D047392:beta-Cyclodextrins; D000082:Acetaminophen; D065347:Hypromellose Derivatives; D008747:Methylcellulose; C031215:betadex