Fluoxetine Capsules

General Notices

Action and use

Selective serotonin reuptake inhibitor; antidepressant.

Definition

Fluoxetine Capsules contain Fluoxetine Hydrochloride.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of fluoxetine, C17H18F3NO

95.0 to 105.0% of the stated amount.

Identification

A. Extract a quantity of the contents of the capsules containing the equivalent of 20 mg of fluoxetine with 10 mL of methanol, filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of fluoxetine hydrochloride (RS 385).
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. Prepare a mixture of 1 volume of diethylamine and 250 volumes of acetonitrile, mix well and adjust the pH to 3.5 with orthophosphoric acid (solution A); a white precipitate may form, keep the mixture well stirred.

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

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

(1) After 45 minutes withdraw a sample of 20 mL of the medium and filter, discarding the first 5 mL of filtrate. Add to 5 mL of filtered medium 2 mL of solution A and mix well.
(2) Add to 5 mL of a 0.0022% w/v solution of fluoxetine hydrochloride BPCRS, 2 mL of solution A and mix well.
chromatographic conditions
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with cyanosilyl silica gel for chromatography (5 µm) (Zorbax 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 ambient column temperature.
(e) Use a detection wavelength of 226 nm.
(f) Inject 50 µL of each solution.
mobile phase

2 volumes of diethylamine, 200 volumes of acetonitrile and 300 volumes of water, the mixture adjusted to pH 3.5 with orthophosphoric acid.

determination of content

Calculate the content of C17H18F3NO in the medium from the chromatograms obtained using the declared content of C17H18F3NO,HCl in fluoxetine hydrochloride BPCRS and taking each mg of C17H18F3NO,HCl to be equivalent to 0.8944 mg of C17H18F3NO.

Related substances

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

(1) Dissolve a quantity of the contents of the capsules containing the equivalent of 20 mg of fluoxetine in sufficient of the mobile phase to produce 10 mL, filter and use the filtrate, discarding the first 2 mL.
(2) 0.001% w/v of fluoxetine hydrochloride BPCRS in the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with cyanosilyl silica gel for chromatography (5 µm) (DuPont Zorbax SB-CN is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use ambient column temperature.
(e) Use a detection wavelength of 215 nm.
(f) Inject 10 µL of each solution.
(g) Allow the chromatography to proceed for twice the retention time of the peak due to fluoxetine hydrochloride.

If necessary, adjust the composition of the mobile phase so that, in the chromatogram obtained with solution (2), the retention time of the peak due to fluoxetine is between 10 and 20 minutes.

mobile phase

35 volumes of acetonitrile and 65 volumes of a solution containing 1 volume of triethylamine and 99 volumes of water, and adjusting the pH to 6.0 with orthophosphoric acid.

limits

In the chromatogram obtained with solution (1):

the area of any secondary peak is not greater than half the area of the peak in the chromatogram obtained with solution (2) (0.25%);

the area of not more than two such peaks is greater than 0.2 times the area of the peak in the chromatogram obtained with solution (2) (0.1%);

and the sum of the areas of all the secondary peaks is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).

Assay

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

(1) Dissolve a quantity of the mixed contents of 20 capsules containing the equivalent of 20 mg of fluoxetine in sufficient of the mobile phase to produce 200 mL, filter and use the filtrate, discarding the first 2 mL.
(2) 0.011% w/v of fluoxetine hydrochloride BPCRS in the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (7.5 cm × 4.6 mm) packed with end-capped octylsilyl silica gel for chromatography (3.5 µm) (DuPont Zorbax RX-C8 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 227 nm.
(f) Inject 20 µL of each solution.
mobile phase

33 volumes of a solution containing 0.3% w/v of glacial acetic acid and 0.64% w/v of sodium pentanesulfonate, adjusted to pH 5.0 with 5m sodium hydroxide, and 67 volumes of methanol.

determination of content

Calculate the content of C17H18F3NO in the capsules from the chromatograms obtained using the declared content of C17H18F3NO,HCl in fluoxetine hydrochloride BPCRS and taking each mg of C17H18F3NO,HCl to be equivalent to 0.8944 mg of C17H18F3NO.

Labelling

The quantity of active ingredient is stated in terms of the equivalent amount of fluoxetine.

IMPURITIES

The impurities limited by the requirements of this monograph include impurities A and B listed under Fluoxetine Hydrochloride.