Edition: BP 2025 (Ph. Eur. 11.6 update)
Carbamazepine Oral Suspensions from different manufacturers, whilst complying with the requirements of the monograph, are not interchangeable, unless justified and authorised.
Action and use
Antiepileptic.
DEFINITION
Carbamazepine Oral Suspension is a suspension of Carbamazepine in a suitable vehicle.
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 oral suspension complies with the requirements stated under Oral Liquids and with the following requirements.
Content of carbamazepine, C15H12N2O
95.0 to 105.0% of the stated amount.
IDENTIFICATION
To a quantity of the oral suspension containing 100 mg of Carbamazepine add 20 mL of 0.1M sodium hydroxide and extract with 3 successive 20-mL quantities of dichloromethane.Dry the combined extracts over anhydrous sodium sulfate and evaporate the dichloromethane.The infrared absorption spectrum of the residue, is concordant with the reference
spectrum of carbamazepine (RS 406).
TESTS
Acidity
pH, 3.5 to 4.5, Appendix V L.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake, with the aid of ultrasound, a quantity of the oral suspension containing 0.2 g of Carbamazepine with 50 mL of methanol, cool and dilute to 100 mL with water.Centrifuge 10 mL of the solution, transfer 5 mL of the supernatant liquid to a 10-mL volumetric flask and dilute to volume with methanol (50%).
(2) Dilute 1 volume of solution (1) to 50 volumes with methanol (50%) and dilute 1 volume of the resulting solution to 10 volumes with methanol (50%).
(3) Dilute 5 mg each of carbamazepine BPCRS and carbamazepine impurity A EPCRS in methanol (50%) and dilute to 50 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 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) Inject solution (1) and 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 volumes of trimethylamine 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 principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any secondary peaks is not more 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 weighed quantity of the oral suspension containing 0.2 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 0.2% 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) 5 mg each of carbamazepine BPCRS and carbamazepine impurity A EPCRS in methanol (50%) and dilute to 50 mL with the same solvent. Dilute 1.0 mL of the resulting solution to 50 mL with methanol (50%).
CHROMATOGRAPHIC CONDITIONS
The conditions described under Related substances may be used.
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
Determine the weight per mL of the oral suspension, Appendix V G, and calculate the content of C15H12N2O, weight in volume, using the declared content of C15H12N2O in carbamazepine BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Carbamazepine.
