Amantadine Oral Solution

Viral replication inhibitor (influenza A); dopamine receptor agonist; treatment of influenza and Parkinson's disease.

Amantadine Oral Solution is a solution of Amantadine Hydrochloride in a suitable flavoured vehicle.

The oral solution complies with the requirements stated under Oral Liquids and with the following requirements.

95.0 to 105.0% of the stated amount.

A. Acidify a volume of the oral solution containing 0.1 g of Amantadine Hydrochloride with 1m hydrochloric acid and extract with three 15 mL quantities of ether. Discard the ether layer, add 2m sodium hydroxide to the aqueous layer until it is just alkaline, extract with two 10 mL quantities of dichloromethane, filter the dichloromethane layer through anhydrous sodium sulfate, evaporate the filtrate to dryness under reduced pressure and dry the residue at room temperature over phosphorus pentoxide at a pressure of 2 kPa for 1 hour. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of amantadine (RS 006).

B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) corresponds to that of the principal peak in the chromatogram obtained with solution (2).

Carry out the method described under Assay using 1 µL of the following solution. Mix, with swirling, a volume of the oral solution containing 0.1 g of Amantadine Hydrochloride with 4 mL of a 20% w/v solution of sodium hydroxide, add 10 mL of toluene, shake the mixture for 10 minutes, allow the layers to separate and use the upper layer.

The area of any secondary peak is not greater than 0.3% and the sum of the areas of any secondary peaks is not greater than 1% by normalisation.

Prepare a 0.6% w/v solution of naphthalene (internal standard) in toluene (solution A). Carry out the method for gas chromatography, Appendix III B, using 1 µL of each of the following solutions. For solution (1) mix, with swirling, a weighed quantity of the oral solution containing 0.1 g of Amantadine Hydrochloride with 4 mL of a 20% w/v solution of sodium hydroxide and add 10 mL of solution A. Shake the mixture for 10 minutes, allow the layers to separate and use the upper layer. Prepare solution (2) in the same manner but using 0.1 g of amantadine hydrochloride BPCRS in 10 mL of water in place of the preparation being examined.

The chromatographic procedure may be carried out using a glass column (1.5 m × 4 mm) packed with silanised diatomaceous support (Chromosorb WHP is suitable) and coated with 10% polyethylene glycol compound (Carbowax 20m is suitable) previously treated with a 5% w/v solution of potassium hydroxide in methanol. Maintain at 150° with the inlet port at 180° and the detector at 250° and use a flow rate of 40 mL per minute for the carrier gas.

Calculate the content of C₁₀H₁₇N,HCl using the ratios of the area of the peak corresponding to Amantadine Hydrochloride 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.