Model of Disposition of Drugs Administered into the Human Nasal Cavity

Abstract

A mathematical model was developed to describe the rate processes involved in the disposition of drugs placed in their delivery systems into the human nasal cavity. The model contains first-order parallel and sequential irreversible rate processes representing the convective drug and carrier transport by fluid flow, mucociliary clearance and peristalsis, drug release and absorption, and decomposition of the drug prior to its appearance in the systemic circulation. The numerical values of the parameters used are based on literature data from clearance studies of nonabsorbable markers deposited in the human nasal cavity, and data obtained under a variety of experimental conditions are consistent with the model. The effect of bioadhesive carriers is successfully simulated by reducing the mucociliary clearance rate constants for the transport from the posterior part of the nose into the gastrointestinal tract. The simulation shows that bioadhesion improves bioavailability and reduces the variability in absorption which might be caused by a variable pattern of deposition in the nose. Variable bioavailability could result from removal of the drug from the nasal cavity by sniffing, blowing, or wiping the nose, leading to different drug residence times in the nose. The model simulations further suggest that drug decomposition in the nose, while lowering bioavailability, also reduces variable absorption due to variable residence times of the drug in the nose.