Fluoxetine Delayed-Release Capsules
» Fluoxetine Delayed-Release Capsules contain an amount of Fluoxetine Hydrochloride equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amount of fluoxetine (C17H18F3NO).
Packaging and storage— Preserve in tight containers, and store at controlled room temperature.
USP Reference standards 11
USP Fluoxetine Hydrochloride RS Click to View Structure
USP Fluoxetine Related Compound C RS Click to View Structure
N-Methyl-N-[3-phenyl-3-(4-trifluoromethyl-phenoxy)-propyl]-succinamic acid.
    C21H22F3NO4    409.40
Identification, Infrared Absorption 197F
Test specimen— Transfer the contents of 3 Capsules to a suitable container, and grind to a fine powder. Transfer a portion of the powder, equivalent to about 40 mg of fluoxetine, to a suitable container, and dissolve in 25 mL of 0.1 N hydrochloric acid. Filter, and transfer 10 mL of the solution so obtained to a separatory funnel, add 20 mL of methylene chloride, and mix. Allow the phases to separate, and transfer the organic layer to a small glass container. Evaporate to dryness with the aid of a current of air and mild heat. Redissolve the residue with a few drops of methylene chloride, and transfer to a potassium bromide plate. Dry or evaporate to a thin film with the aid of a stream of nitrogen.
Drug release 711
Apparatus 3: 12 dips per minute (dpm), using a polypropylene 40-mesh screen on the top and bottom of the reciprocating cylinder.
acid stage—
Medium: 0.1 N hydrochloric acid; 250 mL, deaerated. Operate the apparatus for 2 hours at 12 dpm, withdraw an aliquot of the Medium, and allow the apparatus to proceed to the Buffer stage.
Standard solution— Prepare a solution of USP Fluoxetine Hydrochloride RS in Acid stage Medium having a known concentration of about 0.036 mg per mL.
Test solution— Use portions of the solution under test passed through a filter having a 0.45-µm porosity.
Procedure— Determine the amount of C17H18F3NO dissolved from the minimum (most negative) of the first derivative of UV absorbances at about 278 nm in comparison with the Standard solution.
Tolerances— Not more than 10% of the labeled amount of C17H18F3NO is dissolved in 2 hours.
buffer stage—
Medium: pH 6.8 phosphate buffer (prepared by mixing 3 L of 0.1 N hydrochloric acid and 1 L of 0.2 M tribasic sodium phosphate, and adjusting, if necessary, with 1 N hydrochloric acid or 1 N sodium hydroxide to a pH of 6.8 ± 0.05); 250 mL, deaerated. Operate the apparatus for 45 minutes at 12 dpm, and withdraw an aliquot of the Medium.
Standard solution— Prepare a solution of USP Fluoxetine Hydrochloride RS in Buffer stage Medium, having a known concentration of about 0.36 mg per mL.
Test solution— Use portions of the solution under test passed through a filter having a 0.45-µm porosity.
Procedure— Determine the amount of C17H18F3NO dissolved from the difference between the maximum UV absorbance at about 264 nm and the absorbance at 290 nm in comparison with the Standard solution.
Tolerances— Not less than 75% (Q) of the labeled amount of C17H18F3NO is dissolved in 45 minutes.
Uniformity of dosage units 905: meet the requirements.
Chromatographic purity—
Ion-pair solution— Dissolve about 6.5 g of sodium 1-octanesulfonate and 2.9 g of anhydrous sodium acetate in 1 L of water, and adjust with glacial acetic acid to a pH of 5.0.
Mobile phase— Prepare a filtered and degassed mixture of Ion-pair solution and acetonitrile (58:42). Make adjustments if necessary (see System Suitability under Chromatography 621).
Degraded fluoxetine solution— Dissolve a quantity of USP Fluoxetine Hydrochloride RS in 1.0 N sulfuric acid to obtain a solution containing about 2.2 mg per mL. Heat to 85 for 3 hours, and cool to room temperature.
Fluoxetine related compound solution— Dissolve a quantity of USP Fluoxetine Related Compound C RS in Mobile phase to obtain a solution containing about 0.5 mg per mL.
System suitability solution— Transfer about 13.5 mg of USP Fluoxetine Hydrochloride RS to a 100-mL volumetric flask, add 2 mL of Degraded fluoxetine solution and 2 mL of Fluoxetine related compound solution, and dissolve in and dilute with Mobile phase to volume. Transfer 10.0 mL of this solution to a 250-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Detector sensitivity solution— Transfer 2 mL of the System suitability solution to a 25-mL volumetric flask, and dilute with Mobile phase to volume.
Test solution— Weigh and finely powder not fewer than 20 Capsules. Transfer an accurately weighed portion of the powder, equivalent to about 100 mg of fluoxetine, to a 250-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix. Filter before injection.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 215-nm detector and a 4.6-mm × 15-cm column that contains 3.5-µm packing L7. The column temperature is maintained at 30. The flow rate is about 1 mL per minute. Inject the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.49 for ,,-trifluoro-p-cresol, 0.70 for fluoxetine related compound C, and 1.0 for fluoxetine; the resolution, R, between ,,-trifluoro-p-cresol and fluoxetine related compound C is not less than 2.0; and the resolution, R, between fluoxetine related compound C and fluoxetine is not less than 6.0. Chromatograph the Detector sensitivity solution, and record the peak responses as directed for Procedure: the signal-to-noise ratio for the fluoxetine peak is not less than 10.
Procedure— Inject a volume (about 50 µL) of the Test solution into the chromatograph, record the chromatogram for at least three times the retention time of the fluoxetine peak, and measure all of the peak responses. Calculate the percentage of each impurity in the portion of Capsules taken by the formula:
100(ri / rs)
in which ri is the peak response for each impurity, and rs is the sum of the responses of all the peaks: not more than 0.2% of any individual impurity is found, and not more than 0.7% of total impurities is found.
Assay—
Ion-pair solution— Dissolve about 2.9 mL of glacial acetic acid and about 7.1 g of sodium 1-pentanesulfonate in 1 L of water. Adjust with 5 N sodium hydroxide to a pH of 5.0.
Mobile phase— Prepare a filtered and degassed mixture of methanol and Ion-pair solution (67:33). Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution— Dissolve suitable quantities of USP Fluoxetine Hydrochloride RS and ,,-trifluoro-p-cresol in Mobile phase to obtain a solution containing about 110 µg per mL and 20 µg per mL, respectively.
Standard preparation— Dissolve an accurately weighed quantity of USP Fluoxetine Hydrochloride RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.11 mg per mL.
Assay preparation— Remove, as completely as possible, the contents of not fewer than 20 Capsules, and mix. Transfer an accurately weighed portion of the powder, equivalent to about 100 mg of fluoxetine, to a 500-mL volumetric flask, shake by mechanical means for about 10 minutes, and then sonicate for about 5 minutes. Cool the solution to room temperature, dilute with Mobile phase to volume, and mix. Transfer 5.0 mL of this solution to a 10.0-mL volumetric flask. Dilute with Mobile phase to volume, and mix. Filter the solution before injection.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 227-nm detector and a 4.6-mm × 7.5-cm column that contains 3.5-µm packing L7. The flow rate is about 1 mL per minute. The column temperature is maintained at 38. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for ,,-trifluoro-p-cresol and 1.0 for fluoxetine; the resolution, R, between ,,-trifluoro-p-cresol and fluoxetine is not less than 4.0; the tailing factor for the fluoxetine peak is not more than 1.7; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of fluoxetine (C17H18F3NO) in the portion of Capsules taken by the formula:
1000(309.33/345.79)C(rU / rS)
in which 309.33 and 345.79 are the molecular weights of fluoxetine and fluoxetine hydrochloride, respectively; C is the concentration, in mg per mL, of USP Fluoxetine Hydrochloride RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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