Abstract
Systemic drug delivery via the nasal route is a useful and convenient alternative to oral or intravenous administration. However, the duration of drug retention within the nasal cavity is limited because of mucociliary clearance and other factors. To achieve effective nasal drug delivery with sufficient absorption, the permeability of drugs into nasal tissues must be improved.
Some liquid formulations, containing enhancers and mucoadhesive polymers, and powder formulations have been reported to enhance either drug absorption or permeability. However, the influence of these enhancers and polymers on the nasal mucosa must be considered before clinical use.
We have found that nasal suspensions with lower osmolality greatly improve drug permeability, providing an effective delivery system without the addition of any enhancers or novel ingredients.
Suspension formulations containing fluorescein as a model compound were adjusted to different osmolalities by sorbitol, and then administered intranasally to rabits. The blood concentration of fluorescein increased dramatically as the osmolality of the suspension was lowered.
In addition, a preliminary 28-day toxicological study in rabbits on the intranasal administration of low osmolality suspensions produced no significant mucosal injuries. Thus, the enhanced permeability of the fluorescein in this system may not be derived from mucosal injuries.
In conclusion, low osmolality suspensions is useful as a novel nasal drug delivery system to enhance drug permeability without the addition of enhancers. The system appears to be safe and can be used for systemic drug delivery as well as topical drug delivery via the nasal route.
