Purpose. The present study was conducted to evaluate the effects of formula
tion pH and dose on nasal absorption of scopolamine hydrobromide, the singl
e most effective drug available for the prevention of nausea and vomiting i
nduced 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 poi
nts, and plasma scopolamine concentrations were determined by LC-MS/MS.
Results. Following administration of a 0.2 mg dose, the average C-max value
s 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
C-max 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 2
5,721 +/- 5,294 pg.min/mL for formulation pH 4.0, 7.0, and 9.0, respectivel
y. 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.min/mL) as compared to those of pH 4.0 (5
9,573 +/- 13,700 pg.min/mL) and pH 7.0 (55,298 +/- 17,305 pg.min/mL) formul
ations. Both the C-max and AUC values were almost doubled with doubling the
dose. On the other hand, the average T-max values decreased linearly with
a decrease in formulation pH at both doses. For example, at a 0.4 mg dose,
the average T-max 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.