Effects of pH and dose on nasal absorption of scopolamine hydrobromide in human subjects.
OBJECTIVE
The present study was conducted to evaluate the effects of formulation pH and dose on nasal absorption of scopolamine hydrobromide, the single most effective drug available for the prevention of nausea and vomiting induced by motion sickness.


METHODS
Human subjects received scopolamine nasally at a dose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected at different time points, and plasma scopolamine concentrations were determined by LC-MS/MS.


RESULTS
Following administration of a 0.2 mg dose, the average Cmax values were found to be 262+/-118, 419+/-161, and 488+/-331 pg/ mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At the 0.4 mg dose the average Cmax values were found to be 503+/-199, 933+/-449, and 1,308+/-473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a 0.2 mg dose, the AUC values were found to be 23,208+/-6,824, 29,145+/-9,225, and 25,721+/-5,294 pg x min/mL for formulation pH 4.0, 7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value was found to be high for pH 9.0 formulation (70,740+/-29,381 pg x min/mL) as compared to those of pH 4.0 (59,573+/-13,700 pg x min/mL) and pH 7.0 (55,298+/-17,305 pg x min/mL) formulations. Both the Cmax and AUC values were almost doubled with doubling the dose. On the other hand, the average Tmax, values decreased linearly with a decrease in formulation pH at both doses. For example, at a 0.4 mg dose, the average Tmax values were 26.7+/-5.8, 15.0+/-10.0, and 8.8+/-2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively.


CONCLUSIONS
Nasal absorption of scopolamine hydrobromide in human subjects increased substantially with increases in formulation pH and dose.
Ahmed
S
S
Nastech Pharmaceutical Company, Inc., Hauppauge, New York 11788, USA.
Sileno
A P
AP
deMeireles
J C
JC
Dua
R
R
Pimplaskar
H K
HK
Xia
W J
WJ
Marinaro
J
J
Langenback
E
E
Matos
F J
FJ
Putcha
L
L
Romeo
V D
VD
Behl
C R
CR
D000042:Absorption; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D005079:Excipients; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009297:Nasal Mucosa / Q000378:metabolism*; D019999:Pharmaceutical Solutions; D012601:Scopolamine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D005079:Excipients; D018727:Muscarinic Antagonists; D019999:Pharmaceutical Solutions; D012601:Scopolamine