Norgestrel Tablets

General Notices

Action and use

Progestogen.

Definition

Norgestrel Tablets contain Norgestrel. They are coated.

Production

A suitable dissolution test is carried out to demonstrate the appropriate release of norgestrel.

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

Content of norgestrel, C21H28O2

95.0 to 105.0% of the stated amount.

Identification

A. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) To a quantity of the tablets containing 0.15 mg of Norgestrel add 10 mL of methanol (80%), heat on a water-bath at 60° for 10 minutes, shaking occasionally, allow to cool, dilute with methanol (80%) to produce a solution containing 0.00375% w/v of Norgestrel, mix and filter through a membrane with a pore size of 0.45 µm.
(2) 0.004% w/v of norgestrel BPCRS in methanol (80%).
chromatographic conditions
(a) Use a stainless steel column (12.5 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Hypersil ODS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 242 nm.
(f) Inject 20 µL of each solution.
mobile phase

Equal volumes of methanol and 1% w/v of gamma-cyclodextrin in water.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (2), the resolution between the peaks due to levonorgestrel and dextronorgestrel is at least 1.0.

confirmation
The two principal peaks in the chromatogram obtained with solution (1) have the same retention times as the peaks due to levonorgestrel and dextronorgestrel in the chromatogram obtained with solution (2).
B. In the test for Uniformity of content, 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

Related substances

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

(1) Add 5 mL of a mixture of equal volumes of methanol (50%) to a quantity of the powdered tablets containing 0.15 mg of Norgestrel, mix with the aid of ultrasound for 30 minutes, stir vigorously for 15 minutes, centrifuge and use the supernatant liquid.
(2) Dilute 1 volume of solution (1) to 100 volumes with methanol (50%).
(3) 0.004% w/v each of ethinylestradiol BPCRS and norgestrel BPCRS in methanol (50%).
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS 2 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.2 mL per minute.
(d) Use a column temperature of 30°.
(e) Use a detection wavelength of 220 nm.
(f) Inject 200 µL of each solution.
(g) Allow the chromatography to proceed for twice the retention time of norgestrel.
mobile phase

100 volumes of methanol, 240 volumes of acetonitrile and 500 volumes of water.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to ethinylestradiol and norgestrel is at least 12.

limits

In the chromatogram obtained with solution (1):

the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%);

the sum of the areas of any such peaks is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (2%).

Uniformity of content

Tablets containing less than 2 mg and/or less than 2% w/w of Norgestrel comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) To 1 tablet add 5 mL of the mobile phase, heat on a water bath at 60° for 15 minutes while shaking, disperse with the aid of ultrasound for 5 minutes, centrifuge and use the clear supernatant liquid. Dilute, if necessary, with the mobile phase to produce a solution containing 0.0015% w/v of Norgestrel.
(2) 0.0015% w/v of norgestrel BPCRS in the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (12.5 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Hypersil ODS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.3 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 220 nm.
(f) Inject 25 µL of each solution.
mobile phase

Equal volumes of acetonitrile and water.

determination of content

Calculate the content of C21H28O2 in each tablet using the declared content of C21H28O2 in norgestrel BPCRS.

Assay

Use the average of the individual results determined in the test for Uniformity of content.