Chlordiazepoxide Tablets

General Notices

Chlordiazepoxide Hydrochloride Tablets

Action and use

Benzodiazepine.

Definition

Chlordiazepoxide Tablets contain Chlordiazepoxide Hydrochloride.

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

Content of chlordiazepoxide, C16H14ClN3O

95.0 to 105.0% of the stated amount.

Identification

A. Shake 10 whole tablets with 150 mL of 0.1m hydrochloric acid for 20 minutes, add sufficient 0.1m hydrochloric acid to produce 250 mL and filter. Dilute 10 mL of the filtrate with sufficient 0.1m hydrochloric acid to produce a solution containing the equivalent of 0.0010% w/v of chlordiazepoxide. The light absorption, Appendix II B, in the range 230 to 350 nm exhibits two maxima, at 246 nm and 308 nm.
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 for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.

test conditions
(a) Use Apparatus 1, rotating the basket at 100 revolutions per minute.
(b) Use 900 mL of 0.1m hydrochloric acid, at a temperature of 37°, as the medium.
procedure

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, at the maximum at 308 nm, Appendix II B using 0.1m hydrochloric acid in the reference cell.

determination of content

Calculate the total content of chlordiazepoxide, C16H14ClN3O, in the medium taking 327 as the value of A(1%, 1 cm) at the maximum at 308 nm.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared immediately before use and protected from light.

(1) Shake a quantity of powdered tablets containing the equivalent of 20 mg of chlordiazepoxide with 50 mL of the mobile phase, dilute to 100 mL with the mobile phase and filter.
(2) Dilute 3 volume of solution (1) to 100 volumes with the mobile phase.
(3) Dilute 2 volumes of solution (1) to 100 volumes with the mobile phase and dilute 1 volume of this solution to 10 volumes with the mobile phase.
(4) 0.00004% w/v of aminochlorobenzophenone in the mobile phase.
(5) 0.0002% w/v of chlordiazepoxide impurity A EPCRS and 0.0002% w/v of chlordiazepoxide hydrochloride BPCRS in the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Waters Symmetry 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 254 nm.
(f) Inject 10 µL of each solution.
(g) For solutions (1) and (4) allow the chromatography to proceed for 6 times the retention time of the peak due to chlordiazepoxide.
mobile phase

Equal volumes of acetonitrile and water.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (5), the resolution between the peaks due to impurity A and chlordiazepoxide is at least 5.0.

When the chromatograms are recorded under the prescribed conditions the retention times relative to chlordiazepoxide (retention time about 3.6 min) are impurity A, about 0.7 and aminochlorobenzophenone, about 3.9.

limits

In the chromatogram obtained with solution (1):

the area of any peak due to impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (3%);

the area of any peak due to aminochlorobenzophenone is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (0.2%);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.2%);

the sum of all impurities is not greater than 3.4%.

Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (3) (0.1%).

Assay

Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared immediately before use and protected from light.

(1) Weigh and powder 20 tablets. Shake a quantity of powdered tablets containing the equivalent of 20 mg of chlordiazepoxide with 50 mL of the mobile phase, dilute to 100 mL with the mobile phase and filter. Dilute 10 mL of this solution to 100 mL with the mobile phase.
(2) 0.002% w/v of chlordiazepoxide hydrochloride BPCRS in the mobile phase.
(3) 0.0002% w/v of chlordiazepoxide impurity A EPCRS and 0.0002% w/v of chlordiazepoxide hydrochloride BPCRS in 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 resolution between the peaks due to impurity A and chlordiazepoxide is at least 5.0.

determination of content

Calculate the content of C16H14ClN3O in the tablets using the declared content of C16H14ClN3O,HCl in chlordiazepoxide hydrochloride BPCRS. Each mg of C16H14ClN3O,HCl is equivalent to 0.8916 mg of C16H14ClN3O.

Labelling

The quantity of active ingredient is stated in terms of the equivalent amount of chlordiazepoxide.