Mirtazapine Orally Disintegrating Tablets

» Mirtazapine Orally Disintegrating Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of Mirtazapine (C17H19N3).

Packaging and storage— Store at controlled room temperature. Protect from light and moisture.

—

USP Mirtazapine RS

Identification—

A: Infrared Absorption

197K

—

Test specimen— Transfer a quantity of finely powdered Tablets, equivalent to about 30 mg of mirtazapine, to a separatory funnel containing 30 mL of water, and add about 30 mL of n-hexane. Shake vigorously for 5 minutes, and allow the solution to separate into two layers. Filter the n-hexane layer through glass wool, and evaporate to dryness.

Standard specimen— Dissolve about 30 mg of USP Mirtazapine RS to a separatory funnel containing 30 mL of water, and add about 30 mL of n-hexane. Shake vigorously for 5 minutes, and allow the solution to separate into two layers. Filter the n-hexane layer through glass wool, and evaporate to dryness.

B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

Disintegration

701

: not more than 60 seconds.

Dissolution

711

—

Medium: 0.1 N hydrochloric acid; 900 mL.

Apparatus 2: 50 rpm.

Time: 15 minutes.

Determine the amount of mirtazapine dissolved by employing the following method.

Standard solution— Prepare a solution in Medium containing approximately 33 µg of mirtazapine per mL.

Test solution— Pass a portion of the solution under test through a suitable 0.45-µm filter, discarding the first 5 mL.

Procedure— Determine the amount of mirtazapine dissolved by employing UV absorption at the wavelength of maximum absorbance at about 316 nm on the Test solution in comparison with the Standard solution, using a 0.5-cm cell and Medium as the blank. Calculate the percentage of mirtazapine dissolved by the formula:

in which AU and AS are the absorbances obtained from the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of the Standard solution; 900 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and L is the Tablet label claim, in mg.

Tolerances— Not less than 80% (Q) of the labeled amount of mirtazapine is dissolved in 15 minutes.

Uniformity of dosage units

905

: meet the requirements.

Assay—

Diluent— Prepare a mixture of water and acetonitrile (1:1).

Diluted phosphoric acid— Prepare a mixture of water and phosphoric acid (1000:3).

Phosphate buffer— Dissolve about 1 g of monobasic potassium phosphate and about 1.7 g of pentanesulfonic acid sodium salt in 1 L of water. Adjust with Diluted phosphoric acid to a pH of 4.7 ± 0.1, and filter.

Mobile phase— Prepare a mixture of Phosphate buffer and acetonitrile (75:25). Make adjustments if necessary (see System Suitability under Chromatography

621

Standard stock preparation— Dissolve an accurately weighed quantity of USP Mirtazapine RS in Diluent, sonicating if necessary, to obtain a solution having a known concentration of about 0.3 mg per mL.

Standard preparation— Transfer 6.0 mL of Standard stock preparation into a 50-mL volumetric flask, and dilute with Mobile phase to volume. This solution contains 0.036 mg per mL of mirtazapine.

Assay preparation— Grind not fewer than 20 Tablets to a fine powder. Accurately weigh the equivalent of about 60 mg of mirtazapine, based on the label claim, into a 200-mL volumetric flask, and add about 120 mL of Diluent. Sonicate for about 15 minutes, with occasional swirling. Shake mechanically for approximately 30 minutes, and dilute with Diluent to volume. [note—Alternatively, dissolve 10 Tablets in an accurately measured volume of a mixture of acetonitrile and water (9:1) to obtain a solution having about 1.5 mg per mL of Mirtazapine. Shake or stir until the extract is free from lumps. ] Transfer about 40 mL of this solution into a centrifuge tube, and centrifuge at about 3000 RPM for about 10 minutes. Transfer 6.0 mL of the supernatant into a 50-mL volumetric flask, and dilute with Mobile phase to volume. Use the portion filtered through a 0.45-µm polypropylene membrane, and discard at least the first 5 mL of filtrate prior to analysis. This solution contains about 0.036 mg of mirtazapine per mL.

Chromatographic system (see Chromatography

621

)— The liquid chromatograph is equipped with a 290-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1 mL per minute. Chromatograph 20 µL of the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0; and the relative standard deviation of the mirtazapine peak for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the mirtazapine peaks. Calculate the percentage of C17H19N3 in the sample by the formula:

100(CS / CU)(rU / rS)

in which CS is the concentration, in mg per mL, of USP Mirtazapine RS in the Standard preparation; CU is the concentration, in mg per mL, of mirtazapine in the Assay preparation, based on the label claim; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Hariram Ramanathan, M.S. Associate Scientific Liaison 1-301-816-8313	(SM42010) Monographs - Small Molecules 4
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org
701	Margareth R.C. Marques, Ph.D. Senior Scientific Liaison 1-301-816-8106	(GCDF2010) General Chapters - Dosage Forms
711	Margareth R.C. Marques, Ph.D. Senior Scientific Liaison 1-301-816-8106	(GCDF2010) General Chapters - Dosage Forms

USP35–NF30 Page 3934

Pharmacopeial Forum: Volume No. 37(2)