Edition: BP 2025 (Ph. Eur. 11.6 update)
General Notices
Action and use
Viral replication inhibitor (influenza A); dopamine receptor agonist; treatment of influenza and Parkinson’s disease.
DEFINITION
Amantadine Capsules contain Amantadine Hydrochloride.
The capsules comply with the requirements stated under Capsules and with the following requirements.
Content of amantadine hydrochloride, C10H17N,HCl
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the contents of the capsules containing 0.2 g of Amantadine Hydrochloride in 10 mL of 0.1M hydrochloric acid on a water bath and filter. Add 1 mL of 5M sodium hydroxide to the filtrate and extract with 5 mL of dichloromethane. Filter the lower layer through anhydrous sodium sulfate, wash the sodium sulfate with 2 mL of dichloromethane and evaporate the solution to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of amantadine (RS 006).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 75 revolutions per minute.
(b) Use 900 mL of water, at a temperature of 37°, as the medium.
PROCEDURE
Carry out the method for gas chromatography, Appendix III B, using the following solutions. Prepare a 0.6% w/v solution of naphthalene (internal standard) in toluene (solution A).
(1) After 45 minutes withdraw a sample of the medium and filter. Transfer 3 mL to a centrifuge tube. Add 1 mL of 5M sodium hydroxide and 2 mL of solution A. Shake the tube for approximately 10 minutes and allow the layers to separate. Use the top layer for injection.
(2) To 3 mL of a 0.011% w/v solution of amantadine hydrochloride BPCRS in the medium, add 1 mL of 5M sodium hydroxide and 2 mL of solution A. Shake the flask for approximately 10 minutes and allow the layers to separate. Use the top layer for injection.
CHROMATOGRAPHIC CONDITIONS
(a) Use a fused silica capillary column (30 m × 0.25 mm) bonded with a 0.25-μm layer of methylpolysiloxane (Agilent DB-1 is suitable).
(b) Use helium as the carrier gas at 1 mL per minute.
(c) Use the gradient conditions described below.
(d) Use an inlet temperature of 180°.
(e) Use a flame ionisation detector at a temperature of 250°.
(f) Inject 1 μL of each solution
(g) Use a split ratio of 1:10.
| Time (Minutes) | Temperature | Comment |
| 0-16 | 100°→200° | linear gradient |
| 16-20 | 200° | isothermal |
DETERMINATION OF CONTENT
Calculate the total content of amantadine hydrochloride, C10H17N,HCl, in the medium using the ratios of the area of the peak corresponding to amantadine to the area of the peak due to the internal standard in the chromatograms obtained with solutions (1) and (2), and using the declared content of C10H17N,HCl in amantadine hydrochloride BPCRS.
LIMITS
The amount of amantadine hydrochloride released is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for gas chromatography, Appendix III B using the following solutions.
(1) Dissolve a quantity of the contents of the capsules containing 0.1 g of Amantadine Hydrochloride in 2 mL of water, add 2 mL of a 20% w/v solution of sodium hydroxide and 10 mL of toluene and shake for 10 minutes. Separate the upper layer, dry over anhydrous sodium sulfate and filter.
(2) Dilute 1 volume of solution (1) to 100 volumes with toluene. Further dilute 1 volume to 10 volumes with toluene.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used.
When the chromatograms are recorded under the prescribed conditions, the retention time of amantadine is about 7 minutes.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than 0.2% by normalisation;
the sum of the areas of any secondary peaks is not greater than 1.0% by normalisation.
Disregard any peak with an area less than 0.1% by normalisation.
ASSAY
Weigh the contents of 20 capsules. Mix, and powder if necessary. Carry out the method for gas chromatography, Appendix III B. Prepare a 0.6% w/v solution of naphthalene (internal standard) in toluene (solution A).
(1) Dissolve a quantity of the contents of the capsules containing 0.1 g of Amantadine Hydrochloride in 2 mL of water, add 2 mL of a 20% w/v solution of sodium hydroxide and 10 mL of solution A and shake for 10 minutes. Separate the upper layer, dry over anhydrous sodium sulfate and filter.
(2) Prepare the solution in the same manner as for solution (1) but using 0.1 g of amantadine hydrochloride BPCRS in 10 mL of water in place of the preparation being examined.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used.
DETERMINATION OF CONTENT
Calculate the content of C10H17N,HCl in the capsules using the ratios of the area of the peak corresponding to amantadine to the area of the peak due to the internal standard in the chromatograms obtained with solutions (1) and (2), and using the declared content of C10H17N,HCl in amantadine hydrochloride BPCRS.
