Alverine Capsules

General Notices

Action and use

Smooth muscle relaxant; antispasmodic.

Definition

Alverine Capsules contain Alverine Citrate.

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

Content of alverine citrate, C20H27N,C6H8O7

95.0 to 105.0% of the stated amount.

Identification

Shake a quantity of the contents of the capsules containing 0.12 g of Alverine Citrate with 5 mL of methanol for 5 minutes, filter through a 0.45-µm PTFE filter, evaporate the filtrate to dryness under a stream of nitrogen using a warm water bath and dry the residue for 1 hour at 50° under vacuum. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of alverine citrate (RS 409).

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 2, rotating the paddle at 50 revolutions per minute.
(b) Use 900 mL of 0.1m 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 45 minutes withdraw a 20-mL sample of the medium and filter through a 0.45-µm filter, discarding the first 10 mL of the filtrate. Dilute, if necessary, with 0.1m hydrochloric acid to produce a solution expected to contain about 0.006% w/v of Alverine Citrate.
(2) 0.006% w/v of alverine citrate BPCRS in 0.1m hydrochloric acid.
chromatographic conditions

The chromatographic conditions described under Related substances may be used.

determination of content

Calculate the total content of alverine citrate, C20H27N,C6H8O7, in the medium from the chromatograms obtained and using the declared content of C20H27N,C6H8O7 in alverine citrate BPCRS.

Related substances

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

(1) Add 80 mL of methanol to a quantity of the mixed contents of the capsules containing 0.6 g of Alverine Citrate. Mix with the aid of ultrasound for 1 hour, allow to cool to room temperature, add sufficient methanol to produce 100 mL, mix and filter (Whatman GF/C is suitable).
(2) Dilute 1 volume of solution (1) to 100 volumes with methanol and dilute 1 volume of the resulting solution to 5 volumes with methanol.
(3) alverine citrate impurity standard solution BPCRS.
chromatographic conditions
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with base-deactivated end-capped octadecylsilyl silica gel for chromatography (5 µm) (Hypersil BDS C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 220 nm.
(f) Inject 20 µL of each solution.
(g) Allow the chromatography to proceed for 4 times the retention time of alverine.
mobile phase

0.01m sodium dodecyl sulfate in a mixture of 45 volumes of water and 55 volumes of acetonitrile, adjusting the pH of the mixture to 3.0 with orthophosphoric acid.

system suitability

The test is not valid unless the chromatogram obtained with solution (3) closely resembles the reference chromatogram supplied with alverine citrate impurity standard solution BPCRS.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to alverine citrate impurity A, is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.2%);

the area of any peak corresponding to alverine citrate impurity C is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.5%);

the area of any peak corresponding to alverine citrate impurity D is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.5%);

the area of any other 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 all secondary peaks is not greater than 7 times the area of the principal peak in the chromatogram obtained with solution (2) (1.4%).

Disregard any peak with an area less than 0.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).

Assay

Weigh and powder the contents of 20 capsules. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) To a quantity of the mixed contents of the capsules containing 0.6 g Alverine Citrate add 100 mL of methanol, mix with the aid of ultrasound for 1 hour and add sufficient methanol to produce 500 mL. Stir vigorously for 10 minutes and filter (Cellulose nitrate filter 0.45 µm is suitable). Dilute 1 volume of the filtrate to 2 volumes with water.
(2) Dilute 1 volume of a 0.6% w/v solution of alverine citrate BPCRS in methanol to 10 volumes with water.
(3) alverine citrate impurity standard solution BPCRS.
chromatographic conditions

The chromatographic conditions described under Related substances may be used.

system suitability

The test is not valid unless the chromatogram obtained closely resembles the reference chromatogram supplied with alverine citrate impurity standard solution BPCRS.

determination of content

Calculate the content of C20H27N,C6H8O7 in the capsules using the declared content of C20H27N,C6H8O7 in alverine citrate BPCRS.

STORAGE

Alverine Capsules should be stored in a dry place and not above 25o.

IMPURITIES

The impurities limited by the requirements of this monograph include impurities A, C and D listed under Alverine Citrate.