Nasal Drug Absorption from Powder Formulations: Effect of Fluid Volume Changes on the Mucosal Surface.
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.
Department of Biopharmaceutics, Kyoto Pharmaceutical University.
Akiko
A
Tanaka
Tomoyuki
T
Furubayashi
Yuki
Y
Enomura
Tomoki
T
Hori
Rina
R
Shimomura
Chiaki
C
Maeda
Shunsuke
S
Kimura
Daisuke
D
Inoue
Kosuke
K
Kusamori
Hidemasa
H
Katsumi
Toshiyasu
T
Sakane
Akira
A
Yamamoto
D000281:Administration, Intranasal; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D065588:Nasal Absorption / Q000187:drug effects / Q000502:physiology*; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D011208:Powders; D051381:Rats; D017208:Rats, Wistar; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects / Q000502:physiology*
D005079:Excipients; D011208:Powders