Terfenadine Oral Suspension

Histamine H₁ receptor antagonist; antihistamine.

Terfenadine Oral Suspension is a suspension of Terfenadine in a suitable flavoured vehicle.

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

95.0  to 105.0% of the stated amount.

A.  Shake a volume of the suspension containing 60  mg of Terfenadine with 10  ml of water, centrifuge and discard the liquid phase. Shake the residue sequentially with 10  ml of water, 10  ml of 0.2m sodium hydroxide, 10  ml of water and 10  ml of n-hexane, centrifuge and discard the liquid phase after each extraction. Dissolve the residue in 15  ml of dichoromethane, shake with 2  g of anhydrous sodium sulphate and filter. Add 0.5  ml of the filtrate to 0.3  g of potassium bromide in a mortar, mix with a pestle, warm to remove the solvent and prepare a disc from the resulting mixture. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of terfenadine (RS 392).

B.  In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) dilute a quantity of the oral suspension containing 30  mg of Terfenadine to 70  ml with the mobile phase, shake for 1  hour, add sufficient mobile phase to produce 100  ml, mix and centrifuge. Solution (2) contains 0.00006% w/v of terfenadine impurity A EPCRS (1-[4-(1,1-dimethylethyl)phenyl]-4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butan-1-one) in the mobile phase. Solution (3) contains equal volumes of solution (1) and a solution containing 0.03% w/v of terfenadine impurity A EPCRS in the mobile phase.

The chromatographic procedure may be carried out using (a) a stainless steel column (25  cm × 4.6  mm) packed with end-capped octylsilyl silica gel for chromatography (5 µm) (Lichrosorb RP8 is suitable), (b) 3  volumes of acetonitrile diluted to 5  volumes with diethylammonium phosphate buffer solution pH 6.0 as the mobile phase with a flow rate of 1.0  ml per minute and (c) a detection wavelength of 254  nm.

Inject 20 µl of each solution and continue the chromatography for 5  times the retention time of terfenadine. The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due terfenadine and terfenadine impurity A is at least 5.0.

In the chromatogram obtained with solution (1) the area of any peak corresponding to terfenadine impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%). In the chromatogram obtained with solution (1) peaks due to excipients with long retention times may be present.

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) add about 70  ml of the mobile phase to a weighed quantity of the oral suspension containing 30  mg of Terfenadine and shake for 1  hour. Dilute to 100  ml with the mobile phase, mix, centrifuge and, if necessary, filter the supernatant liquid. Solution (2) contains 0.030% w/v of terfenadine BPCRS in the mobile phase. Solution (3) contains 0.015% w/v of terfenadine impurity A EPCRS in a mixture of equal volumes of solution (2) and the mobile phase.

The chromatographic procedure may be carried out using (a) a stainless steel column (30  cm × 3.9  mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 µm) (µBondapak C18 is suitable), (b) as the mobile phase with a flow rate of 2  ml per minute a mixture of 6  volumes of diethylamine, 350  volumes of water, 500  volumes of acetonitrile and 100  volumes of phosphate buffer prepared by mixing 136.1  g of potassium dihydrogen orthophosphate with 3.2  ml of orthophosphoric acid and adding sufficient water to produce 1000  ml and (c) a detection wavelength of 254  nm.

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is greater than 1.4.

Calculate the content of C₃₂H₄₁NO₂ using the declared content of C₃₂H₄₁NO₂ in terfenadine BPCRS. Determine the weight per ml of the oral suspension, Appendix V G, and calculate the content of C₃₂H₄₁NO₂, weight in volume.