Ramipril Capsules
Action and use
Angiotensin converting enzyme inhibitor.
Definition
Ramipril Capsules contain Ramipril.
Content of ramipril, C23H32N2O5
90.0 to 105.0% of the stated amount.
Identification
Shake a quantity of the contents of the capsules containing 12.5 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 capsules 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 capsules containing 1.25 mg or less 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 1.6 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
Capsules containing less than 2 mg and/or less than 2% w/w of Ramipril comply with the requirements stated under Capsules using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) add 80 mL of 0.1m hydrochloric acid to the contents and shell of one capsule, mix with the aid of ultrasound for 10 minutes and immediately stir magnetically for 15 minutes. Add sufficient 0.1m hydrochloric acid to produce 100 mL and filter through a 0.45-µm glass-fibre filter (Whatman GD/X is suitable). Dilute the resulting solution, if necessary, with sufficient 0.1m hydrochloric acid to produce a solution containing 0.00025% w/v of Ramipril. Solution (2) contains 0.00025% 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 capsule using the declared content of C23H32N2O5 in ramipril BPCRS.
Assay
For capsules 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 capsules containing 2 mg or more and 2% w/w or more of Ramipril
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 capsules 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.