- British Pharmacopoeia Volume III
- Formulated Preparations: Specific Monographs
Ursodeoxycholic Acid Tablets |
Bile acid; treatment of gallstones.
Ursodeoxycholic Acid Tablets contain Ursodeoxycholic Acid. They may be coated.
The tablets comply with the requirements stated under Tablets and with the following requirements.
92.5 to 107.5% of the stated amount.
A. Extract a quantity of the powdered tablets containing 0.1 g of Ursodeoxycholic Acid with 10 mL of ethanol (96%), centrifuge and evaporate the supernatant liquid to dryness in a stream of nitrogen in a water bath at room temperature. Dry the residue at room temperature at a pressure of 0.7 kPa for 2 hours. The infrared absorption spectrum, Appendix II A, of the dried residue is concordant with the reference spectrum of ursodeoxycholic acid (RS 402).
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).
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.
(a) Use Apparatus 1, rotating the basket at 100 revolutions per minute.
(b) Use 900 mL of phosphate buffer as the medium, prepared using 0.68% w/v potassium dihydrogen orthophosphate adjusted to pH 8.0 using 2m sodium hydroxide at a temperature of 40°.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) After 45 minutes withdraw a sample of the dissolution medium and filter.
(2) Dissolve 30 mg of ursodeoxycholic acid BPCRS in 1 mL of ethanol (96%) and dilute to 100 mL with the dissolution medium.
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS is suitable), fitted with a stainless steel guard column packed with the same material (Lichrospher 100-RP 18E is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use a column temperature of 40°C for both columns.
(e) Use a detection wavelength of 210 nm.
(f) Inject 100 µL of each solution.
280 volumes of acetonitrile and 720 volumes of a 0.05m phosphate buffer prepared by dissolving 6.81 g of potassium dihydrogen orthophosphate in 1000 mL of water and adjusting the pH to 6.5 with 2m sodium hydroxide.
Calculate the total content of ursodeoxycholic acid, C24H40O4, in the medium using the declared content of C24H40O4 in ursodeoxycholic acid BPCRS.
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 0.1 g of Ursodeoxycholic Acid with 10 mL of ethanol (96%) with the aid of ultrasound for 15 minutes, centrifuge and use the supernatant liquid.
(2) Prepare a solution containing 0.01% w/v of lithocholic acid BPCRS, 0.05% w/v of cholic acid BPCRS and 0.15% w/v of chenodeoxycholic acid BPCRS in methanol and dilute 1 volume of the resulting solution to 10 volumes with acetone.
(3) Dilute 1 volume of solution (1) to 200 volumes with ethanol (96%).
(a) Use as the coating silica gel (Merck silica gel 60 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 10 cm with mobile phase A, dry in air and then develop the plate to 8 cm in the same direction with mobile phase B.
(e) After removal of the plate, heat at 110° to 120° for 30 minutes. Spray immediately with a solution containing 5% w/v of phosphomolybdic acid in a mixture of 5 mL of sulfuric acid and 95 volumes of glacial acetic acid. Heat the plate for a further 5 to 10 minutes at 110° to 120° until dark blue spots appear on a white or pale blue background.
Mobile phase A 5 volumes of acetic acid, 5 volumes of methanol and 90 volumes of chloroform.
Mobile phase B 1.25 volumes of acetic acid, 50 volumes of ethyl acetate and 50 volumes of 2,2,4-trimethylpentane.
In the chromatogram obtained with solution (1):
any spot corresponding to lithocholic acid is not more intense than the corresponding spot in the chromatogram obtained with solution (2) (0.1%);
any spot corresponding to cholic acid is not more intense than the corresponding spot in the chromatogram obtained with solution (2) (0.5%);
any spot corresponding to chenodeoxycholic acid is not more intense than the corresponding spot in the chromatogram obtained with solution (2) (1.5%);
any other secondary spot is not more intense than the principal spot in the chromatogram obtained with solution (3) (0.5%).
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D using the following solutions in solvent A.
Prepare a solution containing 535 mL of water, 6.0 g of sodium dihydrogen orthophosphate dihydrate, 2.0 g of disodium hydrogen orthophosphate dihydrate, 65 mL of tetrabutylammonium hydroxide solution and 400 mL of acetonitrile (solvent A).
(1) Mix a quantity of the powdered tablets containing 0.3 g of Ursodeoxycholic Acid with 20 mL of solvent A with the aid of ultrasound for 15 minutes, shake intermittently and filter, if necessary.
(2) 1.5% w/v of ursodeoxycholic acid BPCRS.
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS 1 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 a column temperature of 50°.
(e) Use a detection wavelength of 210 nm.
(f) Inject 10 µL of each solution.
(g) Allow the chromatography to proceed for twice the retention time of ursodeoxycholic acid.
500 volumes of acetonitrile and 500 volumes of a solution containing 1.2% w/v of sodium dihydrogen orthophosphate dihydrate, 0.4% w/v of disodium hydrogen orthophosphate dihydrate and 1.08% w/v of tetrabutylammonium hydrogen sulfate in water.
Calculate the content of C24H40O4 in the tablets using the declared content of C24H40O4 in ursodeoxycholic acid BPCRS.