The relationship between in vivo nasal drug clearance and in vitro nasal mucociliary clearance: Application to the prediction of nasal drug absorption

• Published in: European journal of pharmaceutical sciences Vol. 117; pp. 21 - 26
• Main Authors: Inoue, Daisuke, Tanaka, Akiko, Kimura, Shunsuke, Kiriyama, Akiko, Katsumi, Hidemasa, Yamamoto, Akira, Ogawara, Ken-ichi, Kimura, Toshikiro, Higaki, Kazutaka, Yutani, Reiko, Sakane, Toshiyasu, Furubayashi, Tomoyuki
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.05.2018
• Subjects: Mucociliary clearance; Mucosal absorption; Nasal absorption; Nasal formulation; Nasal residence; Prediction system; Prediction system; Nasal residence; Nasal absorption; Nasal formulation; Mucociliary clearance; Mucosal absorption
• ISSN: 0928-0987; 1879-0720; 1879-0720
• DOI: 10.1016/j.ejps.2018.01.032

Drug absorption after nasal application is dependent on drug clearance from the nasal cavity, which is determined by nasal mucociliary clearance (MC). We previously developed an in vitro method to evaluate MC via the translocation velocity of fluorescent microspheres (VFMS) applied to excised rat nasal mucosa. In the present study, the relationship between in vivo nasal MC and in vitro VFMS was examined to optimize our PK model for the prediction of nasal drug absorption. Appropriate inhibitors (propranolol and atropine) and enhancers (terbutaline and acetylcholine chloride) of MC were utilized to modify MC. In vivo clearance of drug from the nasal cavity was determined from the disappearance of fluorescent microspheres (FMS) from the nasal cavity following nasal application to rats. The first order elimination rate constant, kmc, was determined from the disappearance profiles of FMS. kmc was decreased to 35.8% by propranolol and 52.6% by atropine, but increased to 117% by terbutaline and 168% by acetylcholine chloride. A significant linear correlation was observed between kmc and VFMS (r2 = 0.9745, p < 0.001). These results indicate that in vivo kmc can be estimated from the in vitro parameter, VFMS. By introducing linear correlation into our PK model, nasal drug absorption may be precisely estimated, even with changes in MC. [Display omitted]