Paroxetine Tablets

General Notices

Action and use

Selective serotonin reuptake inhibitor; antidepressant.

Definition

Paroxetine Tablets contain Paroxetine Hydrochloride Hemihydrate or Paroxetine Hydrochloride. They are coated.

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

Production

The manufacturing process of Paroxetine Hydrochloride, used in the formulation of Paroxetine Tablets, is validated to show that the content of 4-(4′-fluorophenyl)-1-methyl-1,2,3,6-tetrahydropyridine is not more than 1 ppm.

Content of anhydrous paroxetine hydrochloride, C19H20FNO3,HCl

95.0 to 105.0% of the stated amount.

Identification

A. The light absorption, Appendix II B, in the range 230 to 350 nm of the final solution obtained in the Dissolution test exhibits a maximum at 294 nm.
B. In the Assay, the principal peak in the chromatogram obtained with solution (1) has 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 900 mL of 0.1m hydrochloric acid, at a temperature of 37°, as the medium.
procedure
(1) After 45 minutes withdraw a sample of the medium and filter through a plastic filter with a GF/A filter (Millipore Swinnex is suitable). Measure the absorbance of the filtrate, suitably diluted with the dissolution medium if necessary, at the maximum at 294 nm, Appendix II B, using the dissolution medium in the reference cell.
(2) Measure the absorbance of a suitable solution of paroxetine hydrochloride hemihydrate BPCRS in 0.1m hydrochloric acid at the maximum at 294 nm using the dissolution medium in the reference cell.
determination of content

Calculate the total content of paroxetine hydrochloride, C19H20FNO3,HCl, in the medium from the absorbances obtained and from the declared content of C19H20FNO3,HCl in paroxetine hydrochloride hemihydrate BPCRS.

Related substances

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

(1) Shake a quantity of the powdered tablets containing the equivalent of 50 mg of anhydrous paroxetine hydrochloride with 10 mL of methanol for 30 minutes. Filter through a 0.45-µm membrane filter (Gelman acrodisc GHP is suitable), dilute 1 volume of the solution with 1 volume of mobile phase B.
(2) Dilute 1 volume of solution (1) to 50 volumes with mobile phase A and further dilute 1 volume of the resulting solution to 10 volumes with mobile phase A.
(3) 0.25% w/v of paroxetine impurity standard BPCRS in mobile phase A.
(4) 0.00075% w/v of paroxetine impurity A EPCRS in mobile phase A.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with cyanosilyl silica gel for chromatography (5 µm) (Spherisorb CN is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 265 nm.
(f) Inject 20 µL of each solution.
mobile phase

Mobile phase AEqual volumes of acetonitrile and phosphate buffer pH 6.0 prepared by dissolving 4.9 g of orthophosphoric acid in about 800 mL of water, adjusting the pH to 6.0 with 1m sodium hydroxide and diluting to 1000 mL with water.

Mobile phase BPhosphate buffer pH 6.0 prepared by dissolving 4.9 g of orthophosphoric acid in about 800 mL, adjusting the pH to 6.0 with 1m sodium hydroxide and diluting to 1000 mL with water.

system suitability

The test is not valid unless the chromatogram obtained with solution (3) closely resembles the reference chromatogram supplied with paroxetine impurity standard BPCRS.

limits

Identify any peak due to impurity I in the chromatogram obtained with solution (1), using the chromatogram obtained with solution (3), and multiply the area of this peak by a correction factor of 2.

In the chromatogram obtained with solution (1):

the area of any peak corresponding to impurity A is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (4) (0.3%);

the area of any peak corresponding to impurity I is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);

the sum of the areas of any other secondary peaks is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);

Disregard any peak with with an area less than half the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).

Assay

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

(1) Disperse with the aid of ultrasound a quantity of powdered tablets containing the equivalent of 25 mg of anhydrous paroxetine hydrochloride in 70 mL of water and 5 mL of 0.05m hydrochloric acid. Mix with the aid of ultrasound until all the granular material has dispersed. Add 150 mL of propan-2-ol, shake thoroughly and mix with the aid of ultrasound with occasional swirling for 15 minutes. Cool, add sufficient propan-2-ol to produce 250 mL, filter through a glass microfibre filter (Whatman GF/F is suitable) and use the filtrate.
(2) 0.01% w/v of paroxetine hydrochloride hemihydrate BPCRS in a solution containing 1 volume of 0.01m hydrochloric acid, 14 volumes of water and 35 volumes of propan-2-ol.
(3) 0.25% w/v of paroxetine impurity standard BPCRS in mobile phase A.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with cyanosilyl silica gel for chromatography (5 µm) (Spherisorb CN is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 265 nm.
(f) Inject 20 µL of each solution.
mobile phase

Equal volumes of acetonitrile and phosphate buffer pH 6.0 prepared by dissolving 4.9 g of orthophosphoric acid in about 800 mL of water, adjusting the pH to 6.0 with 1m sodium hydroxide and diluting to 1000 mL with water.

system suitability

The test is not valid unless, the chromatogram obtained with solution (3) closely resembles the chromatogram supplied with paroxetine impurity standard BPCRS.

determination of content

Calculate the content of paroxetine hydrochloride, C19H20FNO3,HCl, in the tablets using the declared content of C19H20FNO3,HCl in paroxetine hydrochloride hemihydrate BPCRS.

Labelling

When the active ingredient is Paroxetine Hydrochloride Hemihydrate, the quantity is stated in terms of the equivalent amount of anhydrous paroxetine hydrochloride.

Storage

Paroxetine Tablets should be protected from light.

Impurities

The impurities limited by the requirements of this monograph include impurity A listed under Paroxetine Hydrochloride and Paroxetine Hydrochloride Hemihydrate, impurities B and I listed under Paroxetine Hydrochloride and the following:

1. 1,2,4-trihydroxybenzene.