[Optimization of Nasal Drug Absorption from Powder Formulations: The Feasibility of Controlling Drug Absorption by the Use of Pharmaceutical Excipients]

Abstract

Nasal application of powder formulations has garnered attention because of its significant potential for systemic drug delivery. Because a powder drug must first diffuse from the formulation and dissolve in the nasal cavity fluid before transepithelial permeation, dissolution and diffusion are distinct but important factors for nasal drug absorption. Since the formulation is directly administered onto the nasal mucosal surface, the effect of excipients on drug absorption may be significant. Therefore, the influence of excipients on nasal drug absorption was evaluated. Three types of hydroxypropyl cellulose (HPC) [HPC (SL), HPC (M), and HPC (H)], lactose, and sodium chloride (NaCl) were used as excipients. Warfarin (WF), piroxicam (PXC), sumatriptan (STP), and norfloxacin (NFX) were selected as model drugs. HPC (M) enhanced the absorption of PXC, while both HPC (M) and HPC (H) enhanced the absorption of STP. All three HPCs failed to enhance the absorption of WF. An increase in the polymerization degree of HPCs decreased the diffusion of drugs in HPC solutions, but prolonged their nasal retention. Lactose and NaCl increased the fluid volume on the nasal mucosal surface by increasing the osmotic pressure, thereby enhancing the nasal absorption of PXC and NFX; however, lactose and NaCl accelerated the nasal clearance of these. These results indicate that nasal drug absorption from powder formulations can be controlled by excipients.

Keywords: hydroxypropyl cellulose; lactose; mucociliary clearance; nasal drug absorption; nasal residence; powder formulation.