Gastro-resistant Bisacodyl Tablets

General Notices

Bisacodyl Tablets

Action and use

Stimulant laxative.

Definition

Gastro-resistant Bisacodyl Tablets contain Bisacodyl. They are made gastro-resistant by enteric coating or by other means.

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

Content of bisacodyl, C22H19NO4

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 similar to that of the principal peak in the chromatogram obtained with solution (2).
B. Extract a quantity of the powdered tablets containing 50 mg of Bisacodyl with 20 mL of dichloromethane, filter, evaporate the filtrate to dryness and dissolve the residue in 10 mL of a 0.5% v/v solution of sulfuric acid. To 2 mL of the solution obtained add sulfuric acid. A reddish violet colour is produced on addition of the concentrated acid.
C. Boil 2 mL of the solution obtained in test B with a little nitric acid; a yellow colour is produced. Cool and add 5m sodium hydroxide; the colour becomes yellowish brown.

TESTS

Dissolution

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

test conditions

First stage

(a) Use Apparatus 1, rotating the basket at 100 revolutions per minute.
(b) Use 500 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 2 hours, withdraw a 10-mL sample of the medium.
(2) Dissolve 50 mg of bisacodyl BPCRS in 50 mL of methanol containing a drop of orthophosphoric acid. Dilute with 0.1m hydrochloric acid to produce a solution containing 0.0005% w/v of bisacodyl BPCRS.
chromatographic conditions
(a) Use a stainless steel column (10 cm × 4.0 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 0.8 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 230 nm.
(f) Inject 20 µL of each solution.
mobile phase

350 volumes of a 0.1% w/v solution of ammonium acetate, adjusted to pH 8.0 with dilute ammonia solution and 650 volumes of acetonitrile.

determination of content

Calculate the total content of C22H19NO4 in the medium using the declared content of C22H19NO4 in bisacodyl BPCRS.

limits

The amount of bisacodyl released is not more than 5% of the stated amount.

After completion of the first stage, remove the basket from the vessel and dip once into a 100-mL beaker containing 80 mL of water. After the water has drained from the basket, transfer the tablet to Apparatus 2 and carry out the procedure described under Final stage.

Final stage

Dissolve 8.9 g of disodium hydrogen orthophosphate and 10 g of sodium lauryl sulfate in 800 mL of water. Adjust to pH 7.5 with 0.1m hydrochloric acid and dilute to 1000 mL with water (solution A).

(a) Use Apparatus 2, rotating the paddle at 100 revolutions per minute.
(b) Use 900 mL of solution A, at a temperature of 37°, as the medium.
procedure
(1) After 60 minutes, withdraw a 10-mL sample of the medium and filter through a 0.45-µm filter, discarding the first 3 mL.
(2) Dissolve 50 mg of bisacodyl BPCRS in 50 mL of methanol containing a drop of orthophosphoric acid. Dilute with solution A to produce a solution containing 0.0056% w/v of bisacodyl BPCRS.
chromatographic conditions

The chromatographic conditions described under Dissolution – First stage may be used.

determination of content

Calculate the total content of C22H19NO4 in the medium using the declared content of C22H19NO4 in bisacodyl BPCRS.

limits

The amount of bisacodyl 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.

A mixture of 4 volumes of glacial acetic acid, 30 volumes of acetonitrile and 66 volumes of water (solution B).

(1) Shake a quantity of the powdered tablets containing 25 mg of Bisacodyl with 40 mL of solution B, dilute to 50 mL with solution B and filter.
(2) Dilute 1 volume of solution (1) to 100 volumes with solution B.
(3) Dissolve the contents of a vial of bisacodyl for system suitability EPCRS in 1 mL of acetonitrile and mix with 1 mL of solution B.
(4) Dissolve 5 mg of bisacodyl for peak identification EPCRS in 2.5 mL of acetonitrile and dilute to 5 mL with solution B.
(5) Dilute 1 volume of solution (2) to 10 volumes with solution B.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with base-deactivated 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 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 265 nm.
(f) Inject 50 µL of each solution.
(g) For solution (1), allow the chromatography to proceed for 3.5 times the retention time of the principal peak.
mobile phase

45 volumes of acetonitrile and 55 volumes of 0.025m ammonium formate previously adjusted to pH 5.0 with anhydrous formic acid.

system suitability

The test is not valid unless the chromatogram obtained with solution (3) closely resembles the reference chromatogram supplied with bisacodyl for system suitability EPCRS.

limits

In the chromatogram obtained with solution (1):

identify any peak corresponding to impurity A and multiply the area of this peak by the following correction factor: 0.7;

the area of any peak corresponding to impurity C is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.5%);

the area of any peak corresponding to impurity A is not greater than 0.8 times the area of the principal peak in the chromatogram obtained with solution (2) (0.8%);

the area of any peak corresponding to impurity E is not greater than half the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);

the area of any peak corresponding to impurity F is not greater than 0.3 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%);

the area of any peak corresponding to impurity D is not greater than 0.2 times the area of the principal peak in the chromatogram obtained with solution (2) (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 (5) (0.1%);

the sum of any other secondary peak, excluding impurities A and C, is not more than 0.5%.

Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (5) (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 10 mg of Bisacodyl with 40 mL of solution B, dilute to 50 mL and filter. Further dilute 1 volume to 4 volumes with solution B described under Related substances.
(2) 0.005% w/v of bisacodyl BPCRS in solution B.
chromatographic conditions

The chromatographic procedure described under Related substances may be used.

system suitability

The test is not valid unless the chromatogram obtained with solution (3) closely resembles the reference chromatogram supplied with bisacodyl for system suitability EPCRS.

determination of content

Calculate the total content of bisacodyl, C22H19NO4, in the tablets using the chromatogram obtained and the declared content of C22H19NO4 in bisacodyl BPCRS.

IMPURITIES

The impurities limited by the requirements of this monograph include those listed under Bisacodyl.