Nasal Drug Absorption from Powder Formulations: Effect of Fluid Volume Changes on the Mucosal Surface

• Tanaka Akiko

  Department of Biopharmaceutics, Kyoto Pharmaceutical University

• Furubayashi Tomoyuki

  School of Pharmacy, Shujitsu University

• Enomura Yuki

  Department of Biopharmaceutics, Kyoto Pharmaceutical University

• Hori Tomoki

  Department of Biopharmaceutics, Kyoto Pharmaceutical University

• Shimomura Rina

  Department of Biopharmaceutics, Kyoto Pharmaceutical University

• Maeda Chiaki

  Department of Biopharmaceutics, Kyoto Pharmaceutical University

• Kimura Shunsuke

  Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts

• Inoue Daisuke

  School of Pharmacy, Shujitsu University

• Kusamori Kosuke

  Department of Biopharmaceutics, Kyoto Pharmaceutical University

• Katsumi Hidemasa

  Department of Biopharmaceutics, Kyoto Pharmaceutical University

• Sakane Toshiyasu

  Department of Biopharmaceutics, Kyoto Pharmaceutical University Department of Pharmaceutical Technology, Kobe Pharmaceutical University

• Yamamoto Akira

  Department of Biopharmaceutics, Kyoto Pharmaceutical University

抄録

The effect of changes in the mucosal fluid volume on the nasal drug absorption of powder formulations was evaluated using warfarin (WF), piroxicam (PXC), and norfloxacin (NFX) as model drugs. Lactose and sodium chloride (NaCl), which are water soluble and small-sized chemicals that increase osmotic pressure after dissolution, were used as excipients to change the mucosal fluid volume. The in vitro study using a Madin–Darby canine kidney (MDCK) cell monolayer indicated that lactose and NaCl, sprayed over the surface of air interface monolayers, increased the fluid volume on the monolayer surface and enhanced the transepithelial transport of the model drugs. The in vivo animal study indicated that the nasal absorption of PXC is enhanced by lactose and NaCl after nasal administration of the powder formulations. This is likely due to the enhanced dissolution of PXC on fluid-rich nasal mucosa and an increase in the effective surface area for drug permeation, which lead to better nasal absorption. However, both excipients failed to increase the nasal absorption of WF and NFX. To clarify the mechanism of the drug-dependent effect of lactose and NaCl, the nasal residence of the formulation was examined using FD70 as a non-absorbable marker. The nasal clearance of FD70 was enhanced by lactose and NaCl, leading to a decrease in the nasal drug absorption. Lactose and NaCl caused no damage to the nasal tissue. These results indicate that the addition of water-soluble excipients such as lactose to powder formulations can enhance the nasal absorption of highly permeable but poorly soluble drugs.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 40 (2), 212-219, 2017

  公益社団法人 日本薬学会

キーワード

• nasal drug absorption
• powder formulation
• lactose
• osmotic pressure
• nasal residence
• mucociliary clearance

詳細情報

• CRID: 1390282679611250560
• NII論文ID: 130005308406
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b16-00787
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 027871650
• PubMed: 28154262
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027871650
• Web Site: https://www.jstage.jst.go.jp/article/bpb/40/2/40_b16-00787/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2017307745
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可