BP 2025 (Ph. Eur. 11.6 update)
Action and use
Antiepileptic.
DEFINITION
Gabapentin Tablets contain Gabapentin.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of gabapentin, C9H17NO2
95.0 to 105.0% of the stated amount.
IDENTIFICATION
The infrared absorption spectrum of the powdered tablets collected in ATR mode, Appendix II A, is concordant with the reference spectrum obtained with gabapentin EPCRS.
TESTS
Dissolution
Comply with 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 sample of the medium and filter. Use the filtered medium, diluted with dissolution medium if necessary, to produce a solution expected to contain 0.011% w/v of Gabapentin.
(2) 0.011% w/v of gabapentin EPCRS in 0.1M hydrochloric acid.
(3) 0.033% w/v of gabapentin EPCRS and 0.0016% w/v of gabapentin impurity A EPCRS in the medium.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel (5 μm) (Hypersil ODS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 210 nm.
(f) Inject 25 μL of each solution.
MOBILE PHASE
1 volume of orthophosphoric acid, 22 volumes of acetonitrile R1, 78 volumes of methanol R1 and 115 volumes of a solution containing 1% w/v of ammonium dihydrogen orthophosphate and 0.17% w/v of sodium decanesulfonate in water.
Adjust the pH to 4.4 with triethylamine.
When the chromatograms are recorded under the prescribed conditions, the retention times of gabapentin and impurity A is about 6 minutes and 8.5 minutes respectively.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to gabapentin impurity A and gabapentin is at least 5.0.
DETERMINATION OF CONTENT
Calculate the total content of C9H17NO2 in the medium from the chromatograms obtained and using the declared content of C9H17NO2
in gabapentin EPCRS.
LIMITS
The amount of gabapentin 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 in a mixture of 1 volume of acetonitrile R1 and 9 volumes of water (solvent A).
(1) Disperse a quantity of powdered tablets containing 0.5 g of Gabapentin in 20 mL of solvent A. Add a sufficient volume of the solvent A to produce 25 mL and filter.
(2) Dilute 1 volume of solution (1) to 100 volumes, dilute 1 volume of the resulting solution to 10 volumes.
(3) 0.02% w/v each of gabapentin EPCRS, gabapentin impurity A EPCRS and gabapentin impurity B EPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with dimethyloctylsilane (5 μm) (Hypersil MOS is suitable).
(b) Use gradient 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 210 nm.
(f) Inject 50 μL of each solution.
MOBILE PHASE
Mobile phase A 0.01M potassium dihydrogen orthophosphate previously adjusted to pH 6.9 with a 10% w/v solution of potassium hydroxide.
Mobile phase B acetonitrile R1.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0→5 | 100 | 0 | isocratic |
| 5→15 | 100→90 | 0→10 | linear gradient |
| 15→45 | 90→70 | 10→30 | linear gradient |
| 45→55 | 70→25 | 30→75 | linear gradient |
| 55→60 | 25 | 75 | isocratic |
| 60→61 | 25→100 | 75→0 | linear gradient |
| 61→70 | 100 | 0 | re-equilibration |
When the chromatograms are recorded under the prescribed conditions, the retention times relative to gabapentin (retention time about 14 minutes) are: impurity B, about 1.1; impurity A, about 2.6.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to and gabapentin and gabapentin impurity B is at least 1.5.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to gabapentin impurity A is not greater than 0.4 times the area of the corresponding peak in the chromatogram obtained with solution (3) (0.4%);
the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.1%);
the sum of the areas of all the secondary peak is not greater than 10 times the area of the principal peak in the chromatogram obtained with solution (2) (1.0%);
Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (2) (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 powdered tablets containing 1.25 g of Gabapentin in 150 mL of mobile phase, add sufficient mobile phase to produce 200 mL and filter.
(2) 0.625% w/v of gabapentin EPCRS in mobile phase.
(3) 0.032% w/v each of gabapentin EPCRS and gabapentin impurity A EPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilylsilica gel (10 μm) (μBondapak C-18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 210 nm.
(f) Inject 50 μL of each solution.
MOBILE PHASE
10 volumes of acetonitrile R1, 35 volumes of methanol R1, 55 volumes of water and 0.1 volumes of a mixture containing 0.35% w/v of potassium dihydrogen orthophosphate and 0.73% w/v of disodium hydrogen orthophosphate previously adjusted to pH 7.0 with either orthophosphoric acid or a 10% w/v solution of potassium hydroxide.
When the chromatograms are recorded under the prescribed conditions, the retention times of gabapentin and impurity A are about 3 minutes and 10 minutes respectively.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to gabapentin and impurity A is at least 10.0.
DETERMINATION OF CONTENT
Calculate the content of C9H17NO2 in the tablets using the declared content of gabapentin in gabapentin EPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities A, B and E listed under Gabapentin.
