Insoluble powder formulation as an effective nasal drug delivery system

Purpose. To evaluate the utility of insoluble powder formulation for nasal systemic drug delivery. Methods. To compare the efficacy of liquid and powder formulations, the nasal absorption of drugs was examined in rats using hydrophilic compounds with various molecular weights (MW) such as phenol red, cyanocobalamin, and fluorescein isothiocyanate (FITC)-Dextrans, and several kinds of powder. Intranasal residence time was also compared among the different formulations. Results. All the drugs examined were absorbed through the nasal mucosa to varying extent; their systemic bioavailability decreased with increasing MW. Insoluble calcium carbonate (CaCO3) powder formulation provided increased absorption of drugs over the wide range of MW from 354 to 77,000 Da. In the case of phenol red, intranasal administration as a CaCO3 powder formulation resulted in a plasma concentration profile similar to that of an intravenous bolus dose due to its very rapid and complete absorption from the nasal cavity. Furthermore, improved bioavailability of FITC-Dextran (MW 4,400; FD-4) was also achieved with other insoluble powders as well as CaCO3, but not with soluble powders such as lactose, d-sorbitol, and d-mannitol. Insoluble powder formulation prolonged the residence time of FD-4 within the nasal cavity. Conclusions. Insoluble powder formulations improve nasal bioavailability predominantly by retarding drug elimination from the absorption site and appear to be effective for nasal systemic drug delivery.