High Quality USP/EP/BP GMP DMF FDA Chlordiazepoxide Capsules CAS NO 58-25-3 Producer

Benzodiazepine.

Definition

Chlordiazepoxide Capsules contain Chlordiazepoxide Hydrochloride.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of chlordiazepoxide hydrochloride, C16H14ClN3O,HCl

A.  Dilute 1  volume of the final solution obtained in the Assay to 2  volumes with 0.1m hydrochloric acid. The light absorption, Appendix II B, in the range 230  to 350  nm exhibits two maxima, at 246  nm and 308  nm.

B.  Shake a quantity of the contents of the capsules containing 25  mg of Chlordiazepoxide Hydrochloride with 2.5  ml of water, add 0.5  ml of 6m ammonia, mix, allow to stand for 5  minutes and filter. The filtrate, after making acidic with 2m nitric acid, yields reaction A characteristic of chlorides, Appendix VI.

Tests

Carry out in subdued light the method for thin-layer chromatography, Appendix III A, using silica gel GF254 as the coating substance and a mixture of 85  volumes of chloroform, 14  volumes of methanol and 1  volume of 13.5m ammonia as the mobile phase. Prepare the following solutions immediately before use in acetone containing 2% v/v of 13.5m ammonia and 8% v/v of water. For solution (1) shake a quantity of the contents of the capsules containing 0.10  g of Chlordiazepoxide Hydrochloride with 10  ml of the solvent mixture, allow to settle and use the clear supernatant liquid. For solution (2) dilute 3  volumes of solution (1) to 100  volumes with the same solvent mixture. Solution (3) contains 0.01% w/v of 2-amino-5-chlorobenzophenone. Apply separately to the plate 2-µl and 20-µl quantities of solution (1), 2 µl of solution (2) and 20 µl of solution (3). After removal of the plate, allow it to dry in air and examine under ultraviolet light (254  nm). Any secondary spot in the chromatogram obtained with 2 µl of solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (3%). Spray the plate with a freshly prepared 1% w/v solution of sodium nitrite in 1m hydrochloric acid, dry it in a current of cold air and spray with a 0.4% w/v solution of N-(1-naphthyl)ethylenediamine dihydrochloride in ethanol (96%). Any violet spot corresponding to 2-amino-5-chlorobenzophenone in the chromatogram obtained with 20 µl of solution (1) is not more intense than the spot in the chromatogram obtained with solution (3) (1%).

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using as the medium 900  ml of 0.1m hydrochloric acid and rotating the basket at 100 revolutions per minute. Measure the absorbance of a layer of suitable thickness of the filtered sample, suitably diluted, if necessary, with 0.1m hydrochloric acid at the maximum at 308  nm, Appendix II B. Calculate the total content of chlordiazepoxide hydrochloride, C16H14ClN3O,HCl, in the medium taking 292 as the value of A(1%, 1  cm) at the maximum at 308  nm.

Carry out the following procedure protected from light. Shake a quantity of the mixed contents of 20 capsules containing 20  mg of Chlordiazepoxide Hydrochloride with 150  ml of 0.1m hydrochloric acid for 20  minutes. Add sufficient 0.1m hydrochloric acid to produce 200  ml and filter. Dilute 10  ml of the filtrate to 50  ml with 0.1m hydrochloric acid and measure the absorbance of the resulting solution at the maximum at 308  nm, Appendix II B. Calculate the content of C16H14ClN3O,HCl taking 292 as the value of A(1%, 1  cm) at the maximum at 308  nm.

Chlordiazepoxide Capsules should be protected from light.