Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Non-nucleoside reverse transcriptase inhibitor; antiviral (HIV).
DEFINITION
Nevirapine Oral Suspension is a suspension of Nevirapine Hemihydrate in a suitable vehicle.
The oral suspension complies with the requirements stated under Oral Liquids and with the following requirements.
Content of nevirapine, C15H14N4O
95.0 to 105.0% of the stated amount.
IDENTIFICATION
In the Assay, record the UV spectrum of the principal peak in the chromatograms obtained with solutions (1) and (2) with a diode array detector in the range of 190 to 400 nm.
The UV spectrum of the principal peak in the chromatogram obtained with solution (1) is concordant with that of the peak in the chromatogram obtained with solution (2);
the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the peak in the chromatogram obtained with solution (2).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 25 revolutions per minute.
(b) Use 900 mL of 0.1M hydrochloric acid, at a temperature of 37°, as the medium.
PROCEDURE
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Solution A: equal volumes of ethanol and water.
(1) Shake the oral suspension for 30 seconds and place a volume equivalent to one dose into each dissolution vessel. After 45 minutes withdraw a sample of the medium and filter (a 0.45-μm Nylon filter is suitable). Use the filtered medium, diluted with the dissolution medium, if necessary, to produce a solution expected to contain the equivalent of 0.0056% w/v of nevirapine.
(2) 1.4% w/v of nevirapine BPCRS in solution A. Dilute with the dissolution medium to produce a solution containing 0.0056% w/v of nevirapine BPCRS.
(3) 0.5% w/v of nevirapine BPCRS and 0.75% w/v of methyl parahydroxybenzoate in solution A. Dilute with the dissolution medium to produce a solution containing 0.004% w/v of nevirapine BPCRS and 0.006% w/v of methyl parahydroxybenzoate.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 3.9 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Symmetry C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 214 nm.
(f) Inject 10 μL of each solution.
MOBILE PHASE
23 volumes of acetonitrile R1 and 77 volumes of water R1.
When the chromatograms are recorded under the prescribed conditions the retention time of nevirapine is about 5 minutes.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to nevirapine and methyl parahydroxybenzoate is at least 5.0.
DETERMINATION OF CONTENT
Calculate the total content of nevirapine, C15H14N4O, in the medium from the chromatograms obtained and using the declared content of C15H14N4O in nevirapine BPCRS.
LIMITS
The amount of nevirapine released is not less than 80% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Mix with the aid of ultrasound a quantity of the oral suspension containing the equivalent of 60 mg of nevirapine in 40 mL of methanol, and dilute to 200 mL with water.
(2) Dilute 1 volume of solution (1) to 100 volumes with water. Dilute 1 volume of this solution to 5 volumes with water.
(3) Dissolve the contents of a vial of nevirapine for peak identification EPCRS in 2 mL of methanol (80%).
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with cyanosilyl silica gel for chromatography (3.5 µm) (Zorbax SB-CN is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use a column temperature of 35°.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
MOBILE PHASE
Solution B: Dissolve 6.8 g of potassium dihydrogen orthophosphate in 950 mL of water, and adjust to pH 3.0 with orthophosphoric acid. Dilute to 1000 mL with water and filter through a 0.45-µm membrane filter.
Mobile phase A: 3 volumes of acetonitrile and 97 volumes of solution B.
Mobile phase B: 24 volumes of acetonitrile and 76 volumes of solution B.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-3 | 100 | 0 | isocratic |
| 3-33 | 100→0 | 0→100 | linear gradient |
| 33-34 | 0→100 | 100→0 | linear gradient |
| 34-42 | 100 | 0 | re-equilibration |
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to nevirapine (retention time about 23 minutes) are: impurity B, about 0.9; impurity A, about 1.1; impurity C, about 1.2
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3):
the resolution between the peaks due to impurity B and nevirapine is at least 1.7. the resolution between the peaks due to nevirapine and impurity A is at least 3.0.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of all secondary peaks is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%).
Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Mix with the aid of ultrasound a weighed quantity of the oral suspension containing the equivalent of 60 mg of nevirapine in 40 mL of methanol, and dilute to 200 mL with water.
(2) 0.25% w/v of nevirapine BPCRS in methanol. Dilute 3 volumes to 25 volumes with water.
(3) Dissolve the contents of a vial of nevirapine for peak identification EPCRS in 2 mL of methanol (80%).
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity B and nevirapine is at least 1.7.
DETERMINATION OF CONTENT
Determine the weight per mL of the oral suspension, Appendix V G, and calculate the content of nevirapine, C15H14N4O, weight in volume, using the declared content of C15H14N4O in nevirapine BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Nevirapine Hemihydrate.
