Edition: BP 2025 (Ph. Eur. 11.6 update)
Prolonged-release Carbamazepine Tablets
Carbamazepine Prolonged-release Tablets from different manufacturers, whilst complying with the requirements of the monograph, are not interchangeable unless otherwise justified and authorised.
Action and use
Antiepileptic.
DEFINITION
Carbamazepine Prolonged-release Tablets contain Carbamazepine. They are formulated so that the medicament is released over a period of several hours.
PRODUCTION
A suitable dissolution test is carried out to demonstrate the appropriate release of Carbamazepine. The dissolution profile reflects the in vivo performance which in turn is compatible with the dosage schedule recommended by the manufacturer.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of carbamazepine, C15H12N2O
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Boil a quantity of the powdered tablets containing 0.2 g of Carbamazepine with 15 mL of acetone, filter the hot solution, wash the residue with two 5-mL quantities of hot acetone, cool in ice and evaporate the combined filtrates to dryness. The infrared absorption spectrum of the crystals, Appendix II A, is concordant with the reference spectrum of carbamazepine (RS 406).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 0.3 g of Carbamazepine with 100 mL of methanol for 15 minutes. Dilute to 200 mL with water, mix and filter.
(2) Dilute 1 volume of solution (1) to 100 volumes with methanol (50%) and dilute 1 volume of the resulting solution to 5 volumes with the same solvent.
(3) Dissolve 7.5 mg each of carbamazepine BPCRS and carbamazepine impurity A EPCRS in methanol and dilute to 100 mL with the same solvent. Dilute 1.0 mL of the resulting solution to 50 mL with methanol (50%).
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with nitrile silica gel for chromatography (10 μm) (Nucleosil 10 CN is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 230 nm.
(f) Inject 20 μL of each solution.
(g) For solution (1) allow the chromatography to proceed for 10 times the retention time of carbamazepine.
MOBILE PHASE
30 volumes of tetrahydrofuran, 120 volumes of methanol and 850 volumes of water, adding 0.2 volumes of anhydrous formic acid and 0.5 volume of triethylamine to 1000 volumes of the solution.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to carbamazepine and carbamazepine impurity A is at least 1.7.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than the area of the peak due to carbamazepine in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any secondary peaks is not greater than 2.5 times the area of the peak due to carbamazepine in the chromatogram obtained with solution (2) (0.5%).
Disregard any peak with an area less than half the area of the peak due to carbamazepine in the chromatogram obtained with solution (2) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 0.3 g of Carbamazepine with 100 mL of methanol for 15 minutes. Dilute to 200 mL with water, mix, filter and further dilute 1 volume of the filtrate to 5 volumes with methanol (50%).
(2) Prepare a 0.3% w/v solution of carbamazepine BPCRS in methanol and dilute 1 volume of this solution to 2 volumes with water. Dilute 1 volume of the resulting solution to 5 volumes with methanol (50%).
(3) Dissolve 7.5 mg each of carbamazepine BPCRS and carbamazepine impurity A EPCRS in methanol and dilute to 100 mL with the same solvent. Dilute 1.0 mL of the resulting solution to 50 mL with methanol (50%).
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used, with the exception of the run time.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to carbamazepine and carbamazepine impurity A is at least 1.7.
DETERMINATION OF CONTENT
Calculate the content of C15H12N2O in the tablets using the declared content of C15H12N2O in carbamazepine BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Carbamazepine.
