Edition: BP 2025 (Ph. Eur. 11.6 update)
General Notices
Action and use
Histamine H1 receptor antagonist.
DEFINITION
Hydroxyzine Tablets contain Hydroxyzine Hydrochloride.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of hydroxyzine hydrochloride, C21H27ClN2O2,2HCl
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is the same as that of the peak due to hydroxyzine hydrochloride in the chromatogram obtained with solution (2).
B. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions, prepared in a solution containing 1 volume of methanol and 1 volume of dichloromethane (solution A).
(1) Shake a quantity of the powdered tablets containing 100 mg of Hydroxyzine Hydrochloride with 5 mL of solution A, add sufficient solution A to produce 10 mL, centrifuge and use the supernatant liquid.
(2) 1% w/v of hydroxyzine hydrochloride BPCRS.
(3) 0.5% w/v each of hydroxyzine hydrochloride BPCRS and meclozine hydrochloride BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a silica gel G plate.
(b) Use the mobile phase described below.
(c) Apply 2 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air, spray with potassium iodobismuthate solution R2, heat at 110° for 5 minutes and allow to cool.
MOBILE PHASE
1 volume of 13.5M ammonia, 24 volumes of ethanol and 75 volumes of toluene.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated spots.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2).
TESTS
Dissolution
Carry out the procedure protected from light. Comply with 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 900 mL of water, at a temperature of 37°, as the medium.
PROCEDURE
(1) After 45 minutes withdraw a sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary to produce a solution expected to contain 0.0011% w/v of Hydroxyzine Hydrochloride, at the maximum at 230 nm, Appendix II B using water in the reference cell.
(2) Measure the absorbance of a 0.0011% w/v solution of hydroxyzine hydrochloride BPCRS using water in the reference cell.
DETERMINATION OF CONTENT
Calculate the total content of hydroxyzine hydrochloride, C21H27ClN2O2,2HCl, in the medium from the absorbances obtained and using the declared content of C21H27ClN2O2,2HCl in hydroxyzine hydrochloride BPCRS.
LIMITS
The amount of hydroxyzine hydrochloride 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 the mobile phase.
(1) Shake a quantity of the powdered tablets containing 50 mg of Hydroxyzine Hydrochloride with 10 mL of the mobile phase, add sufficient mobile phase to produce 50 mL and filter.
(2) Dilute 2 volumes of solution (1) to 100 volumes. Further dilute 1 volume of this solution to 10 volumes.
(3) 0.1% w/v of hydroxyzine hydrochloride BPCRS.
(4) Dilute 1 volume of solution (1) to 100 volumes. Further dilute 1 volume of the resulting solution to 20 volumes.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Luna C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 230 nm.
(f) Inject 20 μL of each solution.
(g) Allow the chromatography to proceed for 3 times the retention time of hydroxyzine.
MOBILE PHASE
14 volumes of triethylamine, 300 volumes of acetonitrile and 686 volumes of a 0.075% w/v solution of sodium methanesulfonate, adjust the mobile phase to pH 2.7 with sulfuric acid.
When the chromatograms are recorded under the prescribed conditions the retention time of hydroxyzine is about 9 min.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the peak-to-valley ratio is at least 10, where Hp is the height above the baseline of the peak immediately before the peak due to hydroxyzine and Hv is the height above the baseline of the lowest point of the curve separating this peak from the peak due to hydroxyzine.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any secondary peaks is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.05%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 50 mg of Hydroxyzine Hydrochloride with 10 mL of water for 20 minutes, add 125 mL of methanol and shake for a further 30 minutes. Add a sufficient quantity of a 30% v/v solution of acetonitrile to produce 250 mL, filter and dilute 5 volumes of the filtrate to 10 volumes with a 30% v/v solution of acetonitrile.
(2) 0.01% w/v of hydroxyzine hydrochloride BPCRS in a 30% v/v solution of acetonitrile.
(3) 0.01% w/v of hydroxyzine hydrochloride BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3); the peak-to-valley ratio is at least 10, where Hp is the height above the baseline of the peak immediately before the peak due to hydroxyzine and Hv is the height above the baseline of the lowest point of the curve separating this peak from the peak due to hydroxyzine.
DETERMINATION OF CONTENT
Calculate the content of C21H27ClN2O2,2HCl in the tablets using the declared content of C21H27ClN2O2,2HCl in hydroxyzine hydrochloride BPCRS.
