Lofepramine Tablets

General Notices

Action and use

Monoamine reuptake inhibitor; tricyclic antidepressant.

Definition

Lofepramine Tablets contain Lofepramine Hydrochloride. They are coated.

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

Content of lofepramine, C26H27ClN2O

90.0 to 105.0% of the stated amount.

Identification

A. Remove the majority of the coating. Wash the tablet with dichloromethane to remove the remaining coating. Place the tablet core in an ultrasound bath for 30 minutes with 10 mL of dichloromethane, filter the resulting suspension through a 0.45-µm PTFE filter; evaporate the filtrate to dryness using a rotary evaporator and a water bath at 30° and dry the residue at 50° at a pressure not exceeding 2 kPa for 1 hour. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of lofepramine hydrochloride (form B) (RS 399B).
B. In the Assay, the chromatogram obtained with solution (2) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (1).

Test

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of tablets containing the equivalent of 0.35 g of lofepramine for 1 hour with 50 mL of a mixture of 250 volumes of acetonitrile, 250 volumes of water and 1 volume of orthophosphoric acid (85%), dilute the resulting solution to 200 mL with the same solvent mixture, centrifuge and use the supernatant liquid. For solution (2) dilute 1 volume of solution (1) to 100 volumes with the same solvent mixture. Solution (3) contains 0.0002% w/v each of desipramine hydrochloride BPCRS and imipramine hydrochloride BPCRS in the mobile phase.

The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with end-capped octylsilyl silica gel for chromatography (5 µm) (Lichrospher 60 RP-select B is suitable) and maintained at 50°, (b) as the mobile phase with a flow rate of 1.5 mL per minute a 0.09% w/v solution of sodium dodecyl sulfate in a mixture of 550 volumes of acetonitrile, 325 volumes of water and 125 volumes of a buffer solution of pH 1.0 containing 0.015% w/v of glycine, 0.018% w/v of sodium chloride and 0.44% w/v of hydrochloric acid and (c) a detection wavelength of 254 nm.

Inject 20 µL of each solution. For solution (1) allow the chromatography to continue for 4 times the retention time of the principal peak.

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 0.9.

In the chromatogram obtained with solution (1), the area of any secondary peak is not greater than the area of the peak in the chromatogram obtained with solution (2) (1%) and the sum of the areas of any secondary peaks is not greater than twice the area of the peak in the chromatogram obtained with solution (2) (2%). Disregard any peak with a retention time of less than 3 minutes.

Assay

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake 10 tablets for 1 hour with 300 mL of a mixture of 250 volumes of acetonitrile, 250 volumes of water and 1 volume of orthophosphoric acid (85%) and dilute to 500 mL with the same solvent mixture, mix and centrifuge; dilute the supernatant liquid with the same solvent mixture to produce a solution containing the equivalent of 0.028% w/v of lofepramine. Solution (2) contains 0.030% w/v of lofepramine hydrochloride BPCRS in the solvent mixture. Solution (3) contains 0.0002% w/v each of desipramine hydrochloride BPCRS and imipramine hydrochloride BPCRS in the mobile phase.

The chromatographic procedure described under Related substances may be used.

Inject 20 µL of each solution. The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 0.9.

Calculate the content of C26H27ClN2O in the tablets using the declared content of C26H27ClN2O in lofepramine hydrochloride BPCRS.

Storage

Lofepramine Tablets should be protected from light and moisture.

Labelling

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