Co-amilozide Tablets

General Notices

Amiloride and Hydrochlorothiazide Tablets

Action and use

Potassium-sparing diuretic + thiazide diuretic.

Definition

Co-amilozide Tablets contain Amiloride Hydrochloride Dihydrate and Hydrochlorothiazide in the proportions one part of anhydrous amiloride hydrochloride to ten parts of Hydrochlorothiazide.

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

Content of anhydrous amiloride hydrochloride, C6H8ClN7O,HCl

95.0 to 105.0% of the stated amount.

Content of hydrochlorothiazide, C7H8ClN3O4S2

95.0 to 105.0% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 0.1 g of Hydrochlorothiazide with 50 mL of acetone, filter, evaporate the filtrate to dryness and dry the residue at 105° for 1 hour. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of hydrochlorothiazide (RS 178).
B. In the test for Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate, the principal spot in the chromatogram obtained with solution (3) corresponds to that in the chromatogram obtained with solution (4).
C. In the Assay, the retention times of the two principal peaks in the chromatogram obtained with solution (4) correspond to those in the chromatograms obtained with solutions (2) and (3).

TESTS

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using silica gel G as the coating substance and a mixture of 85 volumes of ethyl acetate and 15 volumes of propan-2-ol as the mobile phase. Apply separately to the plate 5 µL of each of the following solutions. For solution (1) shake vigorously a quantity of the powdered tablets containing 50 mg of Hydrochlorothiazide with 10 mL of acetone and filter. For solution (2) dilute 1 volume of solution (1) to 100 volumes with acetone. After removal of the plate, dry it in a current of air and reveal the spots by Method I. Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2). Disregard any spot remaining on the line of application.

Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate

Carry out the method for thin-layer chromatography, Appendix III A, protected from light, using a silica gel precoated plate (Merck silica gel 60 plates are suitable) and a freshly prepared mixture of 90 volumes of 1,4-dioxan and 12 volumes of 3m ammonia as the mobile phase. Apply separately to the plate 10 µL of each of the following solutions. For solution (1) shake a quantity of the powdered tablets containing the equivalent of 17.5 mg of anhydrous amiloride hydrochloride with 10 mL of methanol and centrifuge. Solution (2) contains 0.0010% w/v of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate BPCRS in methanol. For solution (3) dilute 1 volume of solution (1) to 20 volumes with methanol. Solution (4) contains 0.010% w/v of amiloride hydrochloride BPCRS in methanol. After removal of the plate, allow it to dry in air and examine under ultraviolet light (365 nm). Any spot corresponding to methyl 3,5-diamino-6-chloropyrazine-2-carboxylate in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2).

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Solution (1) contains 0.0010% w/v of 4-amino-6-chlorobenzene-1,3-disulfonamide BPCRS in solution (3). For solution (2) dissolve 50 mg of amiloride hydrochloride BPCRS in sufficient methanol to produce 200 mL, to 20 mL of the resulting solution add 4 mL of 0.1m hydrochloric acid and dilute to 100 mL with water. For solution (3) dissolve 50 mg of hydrochlorothiazide BPCRS in a mixture of 20 mL of methanol and 4 mL of 0.1m hydrochloric acid and dilute to 100 mL with water. For solution (4) add a mixture of 20 mL of methanol and 4 mL of 0.1m hydrochloric acid to a quantity of the powdered tablets containing 50 mg of Hydrochlorothiazide, mix with the aid of ultrasound for 15 minutes, dilute to 100 mL with water, mix and filter.

The chromatographic procedure may be carried out using (a) a stainless steel column (20 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 µm) (Nucleosil C18 is suitable), (b) a mixture of 76 volumes of water, 20 volumes of methanol and 4 volumes of phosphate buffer pH 3.0 as the mobile phase with a flow rate of 2 mL per minute and (c) a detection wavelength of 286 nm.

The assay is not valid unless a peak due to 4-amino-6-chlorobenzene-1,3-disulfonamide appears immediately before the principal peak in the chromatogram obtained with solution (1). Increase the sensitivity, if necessary, to obtain at least 10% of full-scale deflection on the chart paper for this peak. The assay is also not valid unless the height of the trough separating the two peaks is less than 10% of the height of the peak due to 4-amino-6-chlorobenzene-1,3-disulfonamide. The resolution between the two peaks may be improved by decreasing the methanol content of the mobile phase.

Calculate the content of C6H8ClN7O,HCl and C7H8ClN3O4S2 using the declared content of C6H8ClN7O,HCl and C7H8ClN3O4S2 in amiloride hydrochloride BPCRS and hydrochlorothiazide BPCRS respectively.

Storage

Co-amilozide Tablets should be protected from light.

Labelling

The quantity of Amiloride Hydrochloride Dihydrate is stated in terms of the equivalent amount of anhydrous amiloride hydrochloride.