Clonidine Tablets

General Notices

Action and use

Alpha₂-adrenoceptor agonist; treatment of hypertension.

Definition

Clonidine Tablets contain Clonidine Hydrochloride.

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

Content of clonidine hydrochloride, C₉H₉Cl₂N₃,HCl

90.0 to 110.0% of the stated amount.

Identification

To a quantity of the powdered tablets containing 0.5 mg of Clonidine Hydrochloride add 30 mL of water and 5 mL of 1m sodium hydroxide. Swirl gently and extract with 20 mL of chloroform. Centrifuge the chloroform layer, dry with anhydrous sodium sulfate, filter and evaporate the filtrate to dryness. Dissolve the residue in 8 mL of 0.01m hydrochloric acid. The resulting solution complies with the following tests.

A. The light absorption, Appendix II B, in the range 245 to 350 nm exhibits maxima at 272 nm and 279 nm and an inflection at 265 nm.

B. Add 1 mL of a 10% w/v solution of ammonium reineckate and allow to stand for 5 minutes. A pink precipitate is produced.

TEST

Uniformity of content

Tablets containing less than 2 mg and/or less than 2% w/w of Clonidine Hydrochloride comply with the requirements stated under Tablets using the following method of analysis.

For tablets containing 0.3 mg or more of Clonidine Hydrochloride, add a suitable volume of citro-phosphate buffer pH 7.6 to one tablet, shake until disintegrated and dilute with citro-phosphate buffer pH 7.6, if necessary, to give a solution containing about 0.0015% w/v of Clonidine Hydrochloride. To 5 mL of the supernatant liquid add 1 mL of a solution containing 0.15% w/v of bromothymol blue and 0.15% w/v of anhydrous sodium carbonate, add 10 mL of chloroform, shake and allow to separate. Filter the chloroform layer through absorbent cotton and dilute 5 mL of the filtrate to 10 mL with boric acid solution. Measure the absorbance of a 2-cm layer of the resulting solution at the maximum at 420 nm, Appendix II B, using 5 mL of boric acid solution diluted to 10 mL with chloroform in the reference cell. Calculate the content of C₉H₉Cl₂N₃,HCl from the absorbance obtained by repeating the procedure using a solution prepared by diluting 5 mL of a 0.030% w/v solution of clonidine hydrochloride BPCRS to 100 mL with citro-phosphate buffer pH 7.6, transferring 5 mL to a separating funnel and completing the procedure described above, beginning at the words ‘add 1 mL of a solution …’ and using the declared content of C₉H₉Cl₂N₃,HCl in clonidine hydrochloride BPCRS.

For tablets containing less than 0.3 mg of Clonidine Hydrochloride, use the same procedure but with a concentration of 0.001% w/v or 0.0005% w/v of Clonidine Hydrochloride as appropriate and with correspondingly smaller concentrations of clonidine hydrochloride BPCRS.

Assay

Weigh and powder 20 tablets. To a quantity of the powder containing 0.15 mg of Clonidine Hydrochloride add 25 mL of citro-phosphate buffer pH 7.6 and shake for 15 minutes. Add 5 mL of water and 1 mL of a solution containing 0.15% w/v of bromothymol blue and 0.15% w/v of anhydrous sodium carbonate and shake to disperse. Add 30 mL of chloroform, shake continuously for 1 minute and centrifuge. To 15 mL of the chloroform layer add 10 mL of boric acid solution and measure the absorbance of the resulting solution at the maximum at 420 nm, Appendix II B, using in the reference cell a solution prepared by diluting 10 mL of boric acid solution to 25 mL with chloroform. Repeat the operation using 5 mL of a 0.003% w/v solution of clonidine hydrochloride BPCRS, adding 20 mL of citro-phosphate buffer pH 7.6 and completing the procedure described above, beginning at the words ‘Add 5 mL of water…’. Calculate the content of C₉H₉Cl₂N₃,HCl in the tablets using the declared content of C₉H₉Cl₂N₃,HCl in clonidine hydrochloride BPCRS.