Mechanism of nasal absorption of drugs I: Physicochemical parameters influencing the rate of in situ nasal absorption of drugs in rats
Huang, C.H.; Kimura, R.; Nassar, R.B.; Hussain, A.
Journal of Pharmaceutical Sciences 74(6): 608-611
ISSN/ISBN: 0022-3549 PMID: 4020646 DOI: 10.1002/jps.2600740605
The effect of rate of perfusion, volume, pH of the perfusate and partition coefficient of the drug on the rate of in situ nasal absorption in rats was examined. The rate constant for the nasal absorption of phenobarbital was evidently independent of the rate of perfusion above a value of 2 ml/min. The nasal absorption of benzoic acid depended on the pH of the perfusate with the benzoate anion being absorbed at a rate 1/4 of that of benzoic acid. The effect of lipid solubility on the extent of nasal absorption was studied using a series of barbiturates. The rate and extent of absorption was dependent on the chloroform-water partition coefficient of the barbiturate. The effect of the volume of the perfusate on the absorption rate constant of phenobarbital, phenol red, tyrosine and propranolol was studied. A linear relationship evidently existed between the rate constant of absorption and the reciprocal of the volume of the perfusate. Using the in situ relationship it was possible to predict in vivo absorption rate constants for propranolol and L-tyrosine when volumes of 0.1 ml were administered. The calculated values for these compounds were close to those determined in in vivo experiments. In situ technique can evidently be used to predict in vivo absorption rate constants.