Ramipril Tablets
Action and use
Angiotensin converting enzyme inhibitor.
Definition
Ramipril Tablets contain Ramipril.
Content of ramipril, C23H32N2O5
90.0 to 105.0% of the stated amount.
Identification
Shake a quantity of the powdered tablets containing 25 mg of Ramipril with 50 mL of acetone, centrifuge for 10 minutes, filter the supernatant liquid through a 0.45-µm filter, evaporate the filtrate to dryness on a water bath and dry the residue for 3 hours at 60°. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of ramipril (RS 417).
TESTS
Dissolution
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
420 volumes of acetonitrile R1 and 580 volumes of a solution containing 1.4% w/v of sodium perchlorate and 0.58% w/v of orthophosphoric acid adjusted to pH 2.5 with triethylamine, and adjust the mixture to pH 2.1 with orthophosphoric acid.
Calculate the total content of ramipril, C23H32N2O5, in the medium using the declared content of C23H32N2O5 in ramipril BPCRS.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
When the chromatograms are recorded under the prescribed conditions, the retention time of ramipril is about 10 minutes and retention times relative to ramipril are about 0.3 for ramipril impurity E (ramiprilat), about 0.5 for ramipril impurity K (diketopiperazine acid impurity), about 0.7 for ramipril impurity A (methyl ester impurity) and about 2.6 for ramipril impurity D (diketopiperazine impurity).
A mixture, adjusted to pH 2.6 with orthophosphoric acid, of 350 volumes of acetonitrile R1 and 680 volumes of a solution adjusted to pH 3.9 with triethylamine, containing 1.4% w/v of sodium perchlorate and 0.58% w/v of orthophosphoric acid.
The test is not valid unless, in the chromatogram obtained with solution (4), the resolution factor between the peaks corresponding to ramipril impurity K and ramipril impurity A is at least 1.0.
For tablets containing more than 1.25 mg of Ramipril
In the chromatogram obtained with solution (1) the combined area of peaks corresponding to ramipril impurity D and ramipril impurity E is not greater than 1.2 times the area of the principal peak in the chromatogram obtained with solution (2) (6.0%); the area of any other secondary peak is not greater than half the area of the principal peak in the chromatogram obtained with solution (3) (0.5%). The sum of the areas of all the secondary peaks is not greater than 1.2 times the area of the principal peak in the chromatogram obtained with solution (2) (6.0%).
For tablets containing 1.25 mg or less of Ramipril
In the chromatogram obtained with solution (1) the combined areas of peak corresponding to ramipril impurity D and ramipril impurity E is not greater than 1.6 times the area of the principal peak in the chromatogram obtained with solution (2) (8.0%); the area of any other secondary peak is not greater than half the area of the principal peak in the chromatogram obtained with solution (3) (0.5%). The sum of the areas of all the secondary peaks is not greater than 1.6 times the area of the principal peak in the chromatogram obtained with solution (2) (8.0%).
Uniformity of content
Tablets containing less than 2 mg and/or less than 2% w/w of Ramipril comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) add 5 mL of 0.1m hydrochloric acid to one tablet, mix with the aid of ultrasound for 10 minutes, dilute, if necessary, with sufficient 0.1m hydrochloric acid to produce a solution containing 0.025% w/v of Ramipril, centrifuge and use the supernatant liquid. Solution (2) contains 0.025% w/v of ramipril BPCRS in 0.1m hydrochloric acid.
The chromatographic conditions described under Dissolution may be used.
Calculate the content of C23H32N2O5 in each tablet using the declared content of C23H32N2O5 in ramipril BPCRS.
Assay
For tablets containing less than 2 mg and/or less than 2% w/w of Ramipril
Use the average of the individual results determined in the test for Uniformity of content.
For tablets containing 2 mg or more and 2% w/w or more of Ramipril
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
The chromatographic conditions described under Dissolution may be used.
Calculate the content of C23H32N2O5 in the tablets using the declared content of C23H32N2O5 in ramipril BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed in the monograph for Ramipril.