Dispersible Doxycycline Tablets

General Notices

Action and use

Tetracycline antibacterial.

Definition

Dispersible Doxycycline Tablets contain Doxycycline Monohydrate in a suitable dispersible basis.

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

Content of anhydrous doxycycline, C22H24N2O8

95.0 to 105.0% of the stated amount.

Identification

A. Carry out the method for thin-layer chromatography, Appendix III A, using silica gel H as the coating substance and a mixture of 6 volumes of water, 35 volumes of methanol and 59 volumes of dichloromethane as the mobile phase. Spray the plate evenly with a 10% w/v solution of disodium edetate the pH of which has been adjusted to 9.0 with 10m sodium hydroxide (about 10 mL for a 100 mm × 200 mm plate). Allow the plate to dry in a horizontal position for at least 1 hour. Immediately before use dry it at 110° for 1 hour. Apply separately to the plate 1 µL of each of the following solutions. For solution (1) shake a quantity of the powdered tablets containing the equivalent of 50 mg of anhydrous doxycycline with 100 mL of methanol for 1 to 2 minutes, centrifuge and use the supernatant liquid. Solution (2) contains 0.05% w/v of doxycycline hyclate BPCRS in methanol. Solution (3) contains 0.05% w/v of each of doxycycline hyclate BPCRS and tetracycline hydrochloride BPCRS in methanol. After removal of the plate, dry it in a current of air and examine under ultraviolet light (365 nm). The principal spot in the chromatogram obtained with solution (1) is similar in position, colour and size to that in the chromatogram obtained with solution (2). The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated spots.
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

Disintegration

Comply with the requirements for Dispersible Tablets.

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using Apparatus 2. Use as the medium 900 mL of a solution prepared by dissolving 2 g of sodium chloride in 7 mL of hydrochloric acid and sufficient water to produce 1000 mL and rotate the paddle at 75 revolutions per minute. Withdraw a sample of 15 mL of the medium and filter. Immediately measure the absorbance of the filtrate, Appendix II B, diluted with the dissolution medium if necessary, at 276 nm using dissolution medium in the reference cell. Measure the absorbance of a suitable solution of doxycycline hyclate BPCRS in the dissolution medium and calculate the total content of anhydrous doxycycline, C22H24N2O8, in the medium using the declared content of C22H24N2O8 in doxycycline hyclate BPCRS.

Light-absorbing impurities

Dissolve a quantity of the powdered tablets as completely as possible in sufficient of a mixture of 1 volume of 1m hydrochloric acid and 99 volumes of methanol to produce a solution containing the equivalent of 1.0% w/v of anhydrous doxycycline and filter. The absorbance of the filtrate at 490 nm is not more than 0.20, calculated with reference to the dried powdered tablets, Appendix II B.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared immediately before use. For solution (1) add a quantity of the powdered tablets containing the equivalent of 80 mg of anhydrous doxycycline to 80 mL of 0.01m hydrochloric acid, mix with the aid of ultrasound and add sufficient 0.01m hydrochloric acid to produce 100 mL. Centrifuge and use the supernatant liquid. Solutions (2) to (5) are solutions in 0.01m hydrochloric acid containing (2) 0.080% w/v of doxycycline hyclate BPCRS, (3) 0.080% w/v of 6-epidoxycycline hydrochloride BPCRS, (4) 0.080% w/v of metacycline hydrochloride BPCRS and (5) 0.0016% w/v each of 6-epidoxycycline hydrochloride BPCRS and metacycline hydrochloride BPCRS. For solution (6) dilute a mixture of 4 volumes of solution (2), 1.5 volumes of solution (3) and 1 volume of solution (4) to 25 volumes with 0.01m hydrochloric acid.

The chromatographic procedure may be carried out using (a) a column (25 cm × 4.6 mm) packed with styrene-divinylbenzene co-polymer (8 µm) with a pore size of 10 nm (PLRP-S from Polymer Laboratories is suitable) and maintained at 60°, (b) as the mobile phase with a flow rate of 1 mL per minute a solution prepared as described below and (c) a detection wavelength of 254 nm. For the mobile phase add 60 g of 2-methylpropan-2-ol to a graduated flask with the aid of 200 mL of water, add 400 mL of phosphate buffer pH 8.0, 50 mL of a 1% w/v solution of tetrabutylammonium hydrogen sulfate previously adjusted to pH 8.0 with 2m sodium hydroxide and 10 mL of a 4% w/v solution of disodium edetate previously adjusted to pH 8.0 with 2m sodium hydroxide and dilute to 1000 mL with water. Inject 20 µL of each solution.

The test is not valid unless, in the chromatogram obtained with solution (6), the resolution factor between the first peak (metacycline) and the second peak (6-epidoxycycline) is at least 1.25 and the resolution factor between the second peak and the third peak (doxycycline) is at least 2.0. If necessary, adjust the content of 2-methylpropan-2-ol in the mobile phase.

In the chromatogram obtained with solution (1) the area of any peak corresponding to metacycline or 6-epidoxycycline is not greater than the area of the corresponding peak in the chromatogram obtained with solution (5) (2%) and the area of any other secondary peak is not greater than 0.25 times the area of the peak corresponding to 6-epidoxycycline in the chromatogram obtained with solution (5) (0.5%).

Loss on drying

When dried at 60° at a pressure of 2 kPa for 2 hours, the powdered tablets lose not more than 6.0% of their weight. Use 1 g.

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) add a quantity of the powdered tablets containing the equivalent of 0.1 g of anhydrous doxycycline to 20 mL of 0.1m hydrochloric acid, mix with the aid of ultrasound until fully dispersed (about 10 minutes), add sufficient water to produce 200 mL, mix, centrifuge and use the supernatant liquid. For solution (2) dissolve 0.115 g of doxycycline hyclate BPCRS in 20 mL of 0.1m hydrochloric acid and add sufficient water to produce 200 mL.

The chromatographic conditions described under Related substances may be used.

Calculate the content of C22H24N2O8 in the tablets using the declared content of C22H24N2O8 in doxycycline hyclate BPCRS.

Labelling

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