Ciprofloxacin Tablets

General Notices

Action and use

Fluoroquinolone antibacterial.

Definition

Ciprofloxacin Tablets contain Ciprofloxacin Hydrochloride.

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

Content of ciprofloxacin, C17H18FN3O3

95.0 to 105.0% of the stated amount.

Identification

A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Add a quantity of the powdered tablets containing the equivalent of 2 g of ciprofloxacin to 750 mL of water, mix with the aid of ultrasound for 20 minutes, add sufficient water to produce 1000 mL and mix. Filter a portion of the resulting suspension (Whatman GF/C filter paper is suitable) and dilute the filtrate with sufficient water to produce a solution containing the equivalent of 0.05% w/v of ciprofloxacin.
(2) 0.058% w/v of ciprofloxacin hydrochloride BPCRS in water.
(3) Mix 1 volume of solution (1) and 1 volume of solution (2).
chromatographic conditions
(a) Use as the coating silica gel F254 (Merck silica gel 60 F254 HPTLC plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 10 µL of each solution, as bands.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in air for 15 minutes and examine under ultraviolet light (254 nm and 365 nm).
mobile phase

10 volumes of acetonitrile, 20 volumes of 13.5m ammonia, 40 volumes of dichloromethane and 40 volumes of methanol.

confirmation

The principal band in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2). The principal band in the chromatogram obtained with solution (3) appears as a single, compact band.

B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is the same as that of the principal peak in the chromatogram obtained with solution (2).

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 water, at a temperature of 37°, as the medium.
procedure
(1) After 30 minutes withdraw a 10 mL sample of the medium and measure the absorbance of the filtered sample, suitably diluted with water, if necessary, at the maximum at 276 nm, Appendix II B, using dissolution medium in the reference cell.
(2) Measure the absorbance of a suitable solution of ciprofloxacin hydrochloride BPCRS in water at the maximum at 276 nm using dissolution medium in the reference cell.
determination of content

Calculate the total content of ciprofloxacin, C17H18FN3O3, in the medium from the absorbances obtained and from the declared content of C17H18FN3O3,HCl in ciprofloxacin hydrochloride BPCRS. Each mg of C17H18FN3O3,HCl is equivalent to 0.9010 mg of C17H18FN3O3.

limits

The amount of ciprofloxacin released is not less than 80% of the stated amount.

Related substances

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

(1) Use solution (1) as described under Assay.
(2) 0.05% w/v of ciprofloxacin impurity standard BPCRS in the mobile phase.
(3) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase and further dilute 1 volume to 2 volumes.
(4) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase and further dilute 1 volume to 5 volumes.
chromatographic conditions

The chromatographic conditions described under Assay may be used.

For solution (1) allow the chromatography to proceed for 2.3 times the retention time of ciprofloxacin.

When the chromatograms are recorded under the prescribed conditions the retention time of ciprofloxacin is about 9 minutes. Retention times relative to ciprofloxacin are: impurity E, about 0.4; impurity F, about 0.5; impurity B, about 0.6; impurity C, about 0.7; impurity D, about 1.2.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (2), the resolution factor between the peaks due to ciprofloxacin impurity B and ciprofloxacin impurity C is at least 1.3.

limits

Identify any peaks in the chromatogram obtained with solution (1) corresponding to ciprofloxacin impurities B, C, D and E using solution (2) and multiply the area of these peaks by the following correction factors: 0.7, 0.6, 1.4 and 6.7 respectively.

In the chromatogram obtained with solution (1):

the area of any peak corresponding to 7-[(2-aminoethyl)amino]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (ciprofloxacin impurity C) is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.5%);

the area of any peak corresponding to 1-cyclopropyl-6-fluoro-7-(piperazin-1-yl)quinolin-4(1H)-one (ciprofloxacin impurity E) is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (4) (0.3%);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (0.2%);

the sum of the areas of all the secondary peaks, excluding the peak corresponding to ciprofloxacin impurity C, is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.5%).

Disregard any peak with an area less than 0.25 times the area of the principal peak in the chromatogram obtained with solution (4) (0.05%).

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Add a quantity of the powdered tablets containing the equivalent of 2 g of ciprofloxacin to 750 mL of the mobile phase, mix with the aid of ultrasound for 20 minutes, add sufficient mobile phase to produce 1000 mL and mix. Filter a portion of the resulting suspension (Whatman GF/C filter is suitable) and dilute the filtrate with sufficient mobile phase to produce a solution containing the equivalent of 0.05% w/v of ciprofloxacin.
(2) 0.058% w/v of ciprofloxacin hydrochloride BPCRS in the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with base-deactivated octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil 120-C18 and LiChrospher 100 RP 18 are suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 278 nm.
(f) Inject 5 µL of each solution.
mobile phase

13 volumes of acetonitrile and 87 volumes of a 0.245% w/v solution of orthophosphoric acid the pH of which has been adjusted to 3.0 with triethylamine.

determination of content

Calculate the content of C17H18FN3O3 in the tablets using the declared content of C17H18FN3O3,HCl in ciprofloxacin hydrochloride BPCRS. Each mg of C17H18FN3O3,HCl is equivalent to 0.9010 mg of C17H18FN3O3.

Labelling

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

Impurities

The impurities limited by the requirements of this monograph include impurities B, C, D, E and F listed under Ciprofloxacin Hydrochloride.