Nasal Absorption of Macromolecules from Powder Formulations and Effects of Sodium Carboxymethyl Cellulose on Their Absorption.
The nasal absorption of macromolecules from powder formulations and the effect of sodium carboxymethyl cellulose (CMC-Na) as a pharmaceutical excipient on their absorption were studied. Model macromolecules were fluorescein isothiocyanate-labeled dextran (average molecular weight of 4.4kDa, FD4) and insulin. The plasma concentration of FD4 after application of the powder containing 50% starch (control) was higher than that after application of the solution, and the absorption from 50% starch powder was enhanced by the substitution of starch with CMC-Na. The fractional absorption of FD4 after administration of the CMC-Na powder formulation was 30% and 40% higher than that after administration from the solution and the starch powder, respectively. The nasal absorption of insulin from the powder and the effect of CMC-Na were similar with those of FD4. The effective absorption of FD4 and insulin after application of powder with CMC-Na could be due to the increase in the nasal residence of FD4 and insulin. No damage in the nasal mucosa or dysfunction of the mucociliary clearance was observed after application of the drug powder and CMC-Na. The present findings indicate that nasal delivery of powder formulations with the addition of CMC-Na as an excipient is a promising approach for improving the nasal absorption of macromolecules.
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Akiko
A
Tanaka
School of Pharmacy, Shujitsu University, Nishikawara, Kita, Okayama 703-8516, Japan.
Tomoyuki
T
Furubayashi
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Akifumi
A
Matsushita
School of Pharmacy, Shujitsu University, Nishikawara, Kita, Okayama 703-8516, Japan.
Daisuke
D
Inoue
Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto 610-0395, Japan.
Shunsuke
S
Kimura
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Hidemasa
H
Katsumi
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.|Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Motoyamakita-machi 4-19-1, Higashinada-ku, Kobe 658-8558, Japan.
Toshiyasu
T
Sakane
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Akira
A
Yamamoto
D000281:Administration, Intranasal; D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage* / Q000737:chemistry; D003911:Dextrans / Q000008:administration & dosage* / Q000737:chemistry; D004339:Drug Compounding; D005079:Excipients / Q000008:administration & dosage* / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry; D008970:Molecular Weight; D065588:Nasal Absorption / Q000187:drug effects*; D009297:Nasal Mucosa / Q000187:drug effects; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats
D003911:Dextrans; D005079:Excipients; D007328:Insulin; D011208:Powders; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D002266:Carboxymethylcellulose Sodium