Terfenadine Tablets

Histamine H₁ receptor antagonist; antihistamine.

Terfenadine Tablets contain Terfenadine.

The tablets comply with the requirements stated under Tablets and with the following requirements.

95.0  to 105.0% of the stated amount.

A.  Shake a quantity of the powdered tablets containing 0.2  g of Terfenadine with 20  ml of dichloromethane, add 10  ml of 0.1m sodium hydroxide and shake again. Wash the dichloromethane layer with 10  ml of water, shake with 2  g of anhydrous sodium sulphate and filter. Add 0.2  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).

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using Apparatus 2 and rotating the paddle at 50 revolutions per minute. Use as the medium 1000  ml of 0.1m hydrochloric acid. Withdraw a sample of 20  ml of the medium and filter. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) dilute the filtered sample, if necessary, with 0.1m hydrochloric acid to give a solution expected to contain about 0.006% w/v of Terfenadine. For solution (2) dilute 1  volume of a 0.06% w/v solution of terfenadine BPCRS in methanol to 10  volumes with 0.1m hydrochloric acid.

The chromatographic procedure described under Assay may be used but with a detection wavelength of 217  nm.

Calculate the total content of C₃₂H₄₁NO₂ in the medium using the declared content of C₃₂H₄₁NO₂ in terfenadine BPCRS.

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) disperse a quantity of the powdered tablets containing 0.15  g of Terfenadine in 75  ml of the mobile phase with the aid of ultrasound for 15  minutes, cool to room temperature, dilute to 100  ml with the mobile phase, mix and filter through a glass microfibre filter (Whatman GF/C is suitable). Solution (2) contains 0.0003% 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 a mixture of 1  volume of solution (1) and 9  volumes of a 0.015% w/v solution containing terfenadine impurity A EPCRS in the mobile phase.

The chromatographic procedure described under Assay may be used but using a detection wavelength of 217  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 peak due to terfenadine and that due to 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.

Weigh and finely powder 20  tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) disperse a quantity of the powdered tablets containing 0.15  g of Terfenadine in 75  ml of the mobile phase with the aid of ultrasound for 15  minutes, cool to room temperature, dilute to 100  ml with mobile phase, mix and filter through a glass microfibre filter (Whatman GF/C is suitable). Solution (2) contains 0.15% w/v of terfenadine BPCRS in the mobile phase. Solution (3) contains 0.015% w/v each of terfenadine BPCRS and 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 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 times of terfenadine. The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peak due to terfenadine and that due to terfenadine impurity A is at least 5.0. In the chromatogram obtained with solution (1) peaks due to excipients with long retention times may be present.

Calculate the content of C₃₂H₄₁NO₂ in the tablets using the declared content of C₃₂H₄₁NO₂ in terfenadine BPCRS.