Intranasal mucociliary clearance of putative bioadhesive polymer gels

Rapid clearance of a drug away from the site of absorption is one factor that limits the bioavailability of compounds administered nasally. The effects of putative bioadhesive polymers including methylcellulose, sodium carboxymethylcellulose, hydroxypropyl-methylcellulose, chitosan glutamate, Carbopol 934P, polyethylene oxide 600K and Pluronic F127 on slowing nasal mucociliary clearance were investigated using a rat model. The clearance of these polymer gels from the nasal cavity was measured by following the removal of fluorescently labeled microspheres incorporated into the formulation. Due to the increased residence times of the gel formulations in the nasal cavity, the clearance rate of each polymer gel was slower than the clearance rate of a control microsphere suspension. The clearance rate constants were in the range of 7-57% of the control clearance constants. Methylcellulose gel (3%) resulted in the most prolonged nasal clearance whereas Carbopol 934P aqueous gel (0.2%,) had the most rapid clearance. A Carbopol 934P gel with propylene glycol and glycerol formal as cosolvents was prepared to investigate the effect of an in situ gelling system on nasal clearance. The initial clearance of this cosolvent gel was not significantly different than the suspension, yet the total mass recovered was significantly lower than the control. The clearance of a 3% methylcellulose gel formulation from a damaged nasal mucosa was also investigated in order to obtain further information about the characteristics of nasal mucociliary clearance. Results showed that from 4 h through the 7th day following the initial damage, although the initial clearance rate constants were slightly higher, the time for 90% of the observed particle clearance was significantly extended and the total masses recovered were significantly lower than those obtained from a non-damaged mucosa.