Terfenadine Tablets

General Notices

Action and use

Histamine H1 receptor antagonist; antihistamine.

Definition

Terfenadine Tablets contain Terfenadine.

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

Content of terfenadine, C32H41NO2

95.0 to 105.0% of the stated amount.

Identification

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 sulfate 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).

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in 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 1000 mL of 0.1m hydrochloric acid, at a temperature of 37°, as the medium.
procedure
(1) After 45 minutes withdraw a 20 mL sample of the medium and filter. 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.
(2) Dilute 1 volume of a 0.06% w/v solution of terfenadine BPCRS in methanol to 10 volumes with 0.1m hydrochloric acid.
chromatographic conditions

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

determination of content

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

1-[4-(1,1-Dimethylethyl)phenyl]-4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butan-1-one

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(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).
(2) 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.
(3) 1 volume of solution (1) and 9 volumes of a 0.015% w/v solution containing terfenadine impurity A EPCRS in the mobile phase.
chromatographic conditions

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

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks is due to terfenadine and terfenadine impurity A is at least 5.0.

limits

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%).

Assay

Weigh and finely powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(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).
(2) 0.15% w/v of terfenadine BPCRS in the mobile phase.
(3) 0.015% w/v each of terfenadine BPCRS and terfenadine impurity A EPCRS in the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 µm) (Lichrosorb RP8 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
(g) For solution (1) allow the chromatography to proceed for 5 times the retention times of terfenadine.

In the chromatogram obtained with solution (1) peaks due to excipients with long retention times may be present.

mobile phase

Dilute 3 volumes of acetonitrile to 5 volumes with diethylammonium phosphate buffer solution pH 6.0.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to terfenadine and terfenadine impurity A is at least 5.0.

determination of content

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