Minocycline Tablets

General Notices

Action and use

Tetracycline antibacterial.

Definition

Minocycline Tablets contain Minocycline Hydrochloride Dihydrate.

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

Content of minocycline, C23H27N3O7

92.5 to 107.5% of the stated amount.

Identification

A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Extract a quantity of the powdered tablets containing the equivalent of 10 mg of minocycline with 20 mL of methanol, centrifuge and use the supernatant liquid.
(2) 0.05% w/v of minocycline hydrochloride BPCRS in methanol.
(3) 0.05% w/v of each of minocycline hydrochloride BPCRS and doxycycline hyclate BPCRS in methanol.
chromatographic conditions
(a) Use silica gel GF254 as the coating substance. Adjust the pH of a 10.0% w/v solution of disodium edetate to 9.0 with 10m sodium hydroxide and spray the solution evenly onto the plate (about 10 mL for a plate 100 mm × 200 mm). Allow the plate to dry in a horizontal position for at least 1 hour. Dry the plate at 110° for 1 hour immediately before use.
(b) Use the mobile phase described below.
(c) Apply 2 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry it in a current of air and examine under ultraviolet light (254 nm).
mobile phase

A mixture of 6 volumes of water, 35 volumes of methanol and 59 volumes of dichloromethane.

system suitability

The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated principal spots.

confirmation

The principal spot in the chromatogram obtained with solution (1) is similar in position and size to that in the chromatogram obtained with solution (2).

B. In the Assay, 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).
C. Shake a quantity of the powdered tablets containing the equivalent of 50 mg of minocycline with 5 mL of water and filter. The filtrate yields reaction A characteristic of chlorides, Appendix VI.

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.

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°± 0.5°, as the medium.
procedure
(1) After 45 minutes withdraw a sample of 10 mL of the medium and filter, discarding the first few mL of filtrate. Dilute the filtered solution, if necessary, with 0.1m hydrochloric acid to give a solution expected to contain the equivalent of about 0.001% w/v of minocycline. Measure the absorbance of the solution at the maximum at 348 nm, Appendix II B, using 0.1m hydrochloric acid in the reference cell.
(2) Measure the absorbance of a 0.001% w/v solution of minocycline hydrochloride BPCRS in 0.1m hydrochloric acid using 0.1m hydrochloric acid in the reference cell.
determination of content

Calculate the total content of minocycline, C23H27N3O7, in the medium from the absorbances obtained and using the declared content of C23H27N3O7,HCl in minocycline hydrochloride BPCRS. Each mg of C23H27N3O7,HCl is equivalent to 0.9261 mg of C23H27N3O7.

Related substances

Carry out the method for liquid chromatography, Appendix III D, protected from light. Store the solutions at a temperature of 2° to 8° and use within 3 hours of preparation.

(1) Shake a quantity of the powdered tablets containing the equivalent of 25 mg of minocycline with 50 mL of water, dilute to 100 mL with the same solvent and filter.
(2) Dilute 1 volume of solution (1) to 50 volumes with water.
(3) Dilute 1.2 volumes of solution (1) to 100 volumes with water.
(4) Dissolve 10 mg of minocycline hydrochloride BPCRS in water and evaporate to dryness on a water bath. Dissolve the residue in 10 mL of mobile phase and add sufficient mobile phase to produce 25 mL.
chromatographic conditions
(a) Use a stainless steel column (20 cm × 4.6 mm) packed with end-capped octylsilyl silica gel for chromatography (5 µm) (Nucleosil 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 280 nm.
(f) Inject 20 µL of each solution.
(g) For solution (1) allow the chromatography to proceed for 1.5 times the retention time of minocycline.
mobile phase

A mixture of 25 volumes of a 0.4% w/v solution of sodium edetate, 27 volumes of dimethylformamide and 50 volumes of a 2.8% w/v solution of ammonium oxalate, adjusted to pH 7.0 using a 10.4% w/v solution of tetrabutylammonium hydroxide.

When the chromatograms are recorded using the prescribed conditions the retention time of minocycline is about 15 minutes.

system suitability

The chromatogram obtained with solution (4) shows a peak with a retention time relative to minocycline of about 0.8 [4-epiminocycline (Ph.Eur. impurity A)].

The test is not valid unless, in the chromatogram obtained with solution (4), the resolution factor between the peaks due to minocycline and 4-epiminocycline is at least 2.0.

limits

In the chromatogram obtained with solution (1):

the area of any peak due to 4-epiminocycline is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (2%);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (1.2%);

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

Disregard any peak with an area less than 0.05 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, protected from light. Store the solutions at a temperature of 2° to 8° and use within 3 hours of preparation.

(1) Shake a quantity of the powdered tablets containing the equivalent of 25 mg of minocycline with 50 mL of water, dilute to 100 mL with the same solvent, filter and dilute 10 mL of the filtrate to 20 mL with water.
(2) 0.0125% w/v of minocycline hydrochloride BPCRS in water.
(3) Dissolve 10 mg of minocycline hydrochloride BPCRS in water and evaporate to dryness on a water bath. Dissolve the residue in 10 mL of mobile phase and add sufficient mobile phase to produce 25 mL.
chromatographic conditions

The chromatographic conditions described under Related substances may be used.

When the chromatograms are recorded using the prescribed conditions the retention time of minocycline is about 15 minutes.

system suitability

The chromatogram obtained with solution (3) shows a peak with a retention time relative to minocycline of about 0.8 [4-epiminocycline (Ph.Eur. impurity A)].

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to minocycline and 4-epiminocycline is at least 2.0.

determination of content

Calculate the content of C23H27N3O7 in the tablets from the chromatograms obtained and using the declared content of C23H27N3O7,HCl in minocycline hydrochloride BPCRS. Each mg of C23H27N3O7,HCl is equivalent to 0.9261 mg of C23H27N3O7.

Labelling

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