Hyoscine Butylbromide Tablets

General Notices

Action and use

Anticholinergic.

Definition

Hyoscine Butylbromide Tablets contain Hyoscine Butylbromide.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of hyoscine butylbromide, C21H30BrNO4

92.5 to 105.0% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 50 mg of Hyoscine Butylbromide with 20 mL of chloroform, filter, evaporate the filtrate to dryness and triturate the residue with 5 mL of acetonitrile. Evaporate to dryness and dry the residue at 50° at a pressure not exceeding 0.7 kPa for 1 hour. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of hyoscine butylbromide (RS 185).
B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).

Tests

Dissolution

Comply with the requirements in the dissolution test for tablets and capsules, Appendix XII B1.

test conditions
(a) Use Apparatus 2, rotating the paddle at 75 revolutions per minute.
(b) Use 500 mL of 0.001m hydrochloric acid, at a temperature of 37°, as the medium.
procedure

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) After 30 minutes withdraw a sample of the medium and filter. Use the filtered medium, diluted with 0.001m hydrochloric acid, if necessary, to produce a solution expected to contain 0.002% w/v of hyoscine butylbromide.
(2) 0.002% w/v of hyoscine butylbromide BPCRS in 0.001m hydrochloric acid
chromatographic conditions
(a) Use a stainless steel column 12.5 cm x 4 mm packed with octadecylsilyl silica gel for chromatography (5 µm) (LiChrospher 60 RP select B is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 210 nm.
(f) Inject 50 µL of each solution.
Solution A Dissolve 2.5 g of sodium heptanesultonate monohydrate in 720 mL of a 0.908% w/v solution of potassium dihydrogen orthophosphate and add 60 mL of a 1.188% w/v solution of disodium hydrogen orthophosphate.
mobile phase

780 volumes of solution A and 240 volumes of acetonitrile R1.

When the chromatograms are recorded under the prescribed conditions, the retention time of hyoscine butylbromide is about 7 minutes.

determination of content

Calculate the total content of C21H30BrNO4 in the medium using the chromatograms obtained and the declared content of C21H30BrNO4 in hyoscine butylbromide BPCRS.

limits

The amount of hyoscine butylbromide released is not less than 75% (Q) of the stated amount.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions in 0.01m hydrochloric acid.

(1) Shake a quantity of tablets containing 20 mg of Hyoscine Butylbromide in 8 mL of 0.01m hydrochloric acid, add sufficient 0.01m hydrochloric acid to produce 10 mL and filter.
(2) Dilute 2 volumes of solution (1) to 100 volumes and dilute 1 volume of this solution to 10 volumes.
(3) 0.0024% w/v of tropic acid.
chromatographic conditions
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped octylsilyl amorphous organosilica polymer (5 µm) (Xterra RP 8 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 210 nm.
(f) Inject 20 µL of each solution.
(g) Allow the chromatography to proceed for twice the retention time of the principal peak.
mobile phase

Dissolve 2 g of sodium dodecyl sulfate in 470 mL of 0.001m hydrochloric acid and 530 mL of methanol R1.

When the chromatograms are recorded under the prescribed conditions, the retention times relative to hyoscine butylbromide (retention time, about 5.5 minutes): tropic acid, 0.2; impurity G, about 1.7.

system suitability

The test is not valid unless:

in the chromatogram obtained with solution (1), the retention time of the peak due to hyoscine butybromide is between 5 and 6 minutes;

in the chromatogram obtained with solution (3) the retention time of the peak due to tropic acid is between 0.6 and 1.6 minutes.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to tropic acid is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (1.2%);

the area of any peak corresponding to impurity G is not greater than 9 times the area of the principal peak in the chromatogram obtained with solution (2) (1.8%);

the area of any other secondary peak is not greater than the area of principal peak in the chromatogram obtained with solution (2) (0.2%);

the sum of all impurities is not greater than 3.40%.

Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions in 0.001m hydrochloric acid.

(1) Mix with the aid of ultrasound a quantity of the powdered tablets containing 40 mg of Hyoscine Butylbromide with 60 mL of the solvent for 15 minutes, dilute to 100 mL with the same solvent, centrifuge and filter.
(2) 0.04% w/v of hyoscine butylbromide BPCRS.
chromatographic conditions
a) Use a stainless steel column (25 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (10 µm) (Lichrosorb 10µ C8 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 210 nm.
(f) Inject 20 µL of each solution.
mobile phase

2.0 g of sodium dodecyl sulfate in a mixture of 370 mL of 0.001m hydrochloric acid and 680 mL of methanol.

determination of content

Calculate the content of C21H30BrNO4 in the tablets using the declared content of C21H30BrNO4 in hyoscine butylbromide BPCRS.

Storage

Hyoscine Butylbromide Tablets should be stored protected from light.

Impurities

The impurities controlled in this monograph include:

A. (1R,2R,4S,5S,7s)-9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-yl (2S)-3-hydroxy-2-phenylpropanoate (hyoscine);
B. (2RS)-3-hydroxy-2-phenylpropanoic acid (tropic acid);
G. (1R,2R,4S,5S,7s,9r)-9-butyl-9-methyl-7-[(2-phenylprop-2-enoyl)oxy]-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane (apo-N-butylhyoscine)