Effects of pH and dose an nasal absorption of scopolamine hydrobromide in human subjects

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.