Tanaka Akiko, Furubayashi Tomoyuki, Tomisaki Manami, Kawakami Mayuko, Kimura Shunsuke, Inoue Daisuke, Kusamori Kosuke, Katsumi Hidemasa, Sakane Toshiyasu, Yamamoto Akira
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan.
School of Pharmacy, Shujitsu University, Kita, Okayama 703-8516, Japan.
Eur J Pharm Sci. 2017 Jan 1;96:284-289. doi: 10.1016/j.ejps.2016.09.028. Epub 2016 Sep 21.
Despite the numerous advantages of powder formulations, few studies have described their nasal drug absorption. The first aim of this study was to compare the drug absorption from powder formulation with that from a liquid formulation in rats. Since pharmaceutical excipients are usually added to most powder formulations, the second aim of the study was to investigate the effect of hydroxypropyl cellulose (HPC) on nasal drug absorption from the powder. Three types of HPC with different polymerization degrees were used: HPC(SL), HPC(M), and HPC(H). The model drugs were warfarin (BCS Class I), piroxicam (BCS Class II), and sumatriptan (BCS Class III). The absorption of these model drugs in the powder form was higher than that from the solution. All HPCs failed to enhance warfarin absorption, while the piroxicam absorption was enhanced only by HPC(M). Sumatriptan absorption was not enhanced by HPC(SL), but by HPC(M) and HPC(H). The differences in nasal absorption of the three model drugs promoted by HPCs depend on the permeability and solubility of the drug. Moreover, the nasal retention of different formulations was increased by HPCs. Because HPCs showed no toxic effect on the nasal epithelium. These findings indicate that powder formulations supplemented with HPC are a valuable and promising approach to increase the nasal absorption of highly soluble and poorly permeable drugs.
尽管粉末制剂有诸多优点，但很少有研究描述其鼻腔药物吸收情况。本研究的首要目的是比较大鼠体内粉末制剂与液体制剂的药物吸收情况。由于大多数粉末制剂通常会添加药用辅料，本研究的第二个目的是研究羟丙基纤维素（HPC）对粉末制剂鼻腔药物吸收的影响。使用了三种不同聚合度的HPC：HPC(SL)、HPC(M)和HPC(H)。模型药物为华法林（BCS I类）、吡罗昔康（BCS II类）和舒马曲坦（BCS III类）。这些模型药物以粉末形式的吸收高于溶液形式。所有HPC均未能增强华法林的吸收，而仅HPC(M)增强了吡罗昔康的吸收。HPC(SL)未增强舒马曲坦的吸收，但HPC(M)和HPC(H)增强了其吸收。HPC促进的三种模型药物鼻腔吸收的差异取决于药物的渗透性和溶解性。此外，HPC增加了不同制剂的鼻腔滞留时间。因为HPC对鼻上皮没有毒性作用。这些发现表明，添加HPC的粉末制剂是增加高溶解性和低渗透性药物鼻腔吸收的一种有价值且有前景的方法。
