Nasal Residence Depending on the Administered Dosage Form: Impact of Formulation Type on the In Vivo Nasal Retention Time of Drugs in Rats

Abstract

Background/Objectives: The precise control of drug absorption through the nasal mucosa following intranasal administration can be achieved through optimal formulation development that considers the nasal retention properties of the administered dosage form. This study aimed to quantitatively elucidate the effect of formulation type on nasal residence time in vivo. Methods: The nasal residence behavior of various formulation types, including solutions, particulates, and powders, was estimated in rats. Furthermore, the effect of mucoadhesive polymers on the nasal residence time was investigated using gel and powder dosage forms of sodium alginate. Results: The nasal retention behavior of the formulation in the nasal cavity differed depending on the dosage form. The polystyrene microparticles and lactose powder, a non-adhesive powder, were quickly eliminated into the nasopharynx, whereas the solution remained in the nasal cavity longer than the other formulations. The clearance behavior of the solution was investigated, and it was found that the solution was quickly transported to the stomach without being retained in the esophagus. The disappearance of the gel and powder with the mucoadhesive polymer was different, with the powder clearing faster. This difference in clearance is thought to be due to the powder being cleared before dissolving and diffusing into the nasal mucus. Conclusions: It has been clearly shown that the nasal residence behavior differed depending on the dosage forms. The addition of mucoadhesive polymers was effective in improving the nasal residence of the drug, and more-effective formulations for nasal application can be developed by combining optimal dosage forms, such as powders and gels.

Keywords: formulation development; intranasal administration; intranasal drug delivery; mucociliary clearance; nasal absorption; nasal formulation; nasal residence time.

Figure 1

Schematic of the drug translation pathway following intranasal administration.

Figure 2

Disappearance of FD-70 following its application at different positions in the nasal cavity. (A) Time profiles of FD-70 remaining in the nasal cavity. (B) Slope of the linear elimination of the α-phase (up to 30 min) plotted on a semi-logarithmic scale. (C) Slope of the linear elimination of the later phase (30–120 min) plotted on a semi-logarithmic scale. Data are expressed as the means of three–five independent experiments, with vertical bars showing S.E.M.

Figure 3

Drug transition from the nasal cavity to the stomach. Time profiles of FD-70 in the nasal cavity, esophagus, and gastric cardia. The cumulative amount of FD-70 in the three parts is shown as a solid black circle. Data are expressed as the means of three–five independent experiments, with vertical bars showing S.E.M. The dotted line represents the remaining amount of 100%.

Figure 4

Disappearance profiles of each dosage form in the nasal cavity following intranasal administration. (A) Time profiles of remaining formulations in the nasal cavity. (B) Slope of the linear elimination of the α-phase (up to 30 min) plotted on a semi-logarithmic scale. (C) Slope of the linear elimination of the later phase (30–120 min) plotted on a semi-logarithmic scale. Data are expressed as the means of three–five independent experiments, with vertical bars showing S.E.M. Statistical significance is represented as ***, p < 0.001; **, p < 0.01; and *, p < 0.05, compared with the solution.

Figure 5

Disappearance profiles of mucoadhesive powers in the nasal cavity following intranasal administration. (A) Time profile of the powder remaining in the nasal cavity. (B) Slope of the linear elimination of the α-phase (up to 30 min) plotted on a semi-logarithmic scale. (C) Slope of the linear elimination of the later phase (30–120 min) plotted on a semi-logarithmic scale. Data are expressed as the means of three–five independent experiments, with vertical bars showing S.E.M. Statistical significance is represented as *, p < 0.05, compared with the Powder/Lac.

Figure 6

Disappearance profiles of mucoadhesive gel and power in the nasal cavity after intranasal administration. (A) Time profile of formulations remaining in the nasal cavity. (B) Slope of the linear elimination of the α-phase (up to 30 min) plotted on a semi-logarithmic scale. (C) Slope of the linear elimination of the later phase (30–120 min) plotted on a semi-logarithmic scale. Data are expressed as the means of three–five independent experiments, with vertical bars showing S.E.M. Statistical significance is represented as ** p < 0.01 and * p < 0.05, compared with Powder/Lac.