Action and use
Non-nucleoside reverse transcriptase inhibitor; antiviral (HIV).
DEFINITION
Nevirapine Tablets contain Nevirapine.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of nevirapine, C15H14N4O
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the powdered tablets containing 25 mg of Nevirapine with 10 mL of dichloromethane and filter through a sintered-glass funnel. Using a glass syringe, pass the filtrate through a 0.45-μm PTFE syringe filter and dry the residue at 105° for 1 hour. Triturate the dried residue with 0.2 g of potassium bromide. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of nevirapine (RS 507).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use as the medium 900 mL of a phosphate buffer, at a temperature of 37°, prepared in the following manner. Mix 3.9 mL of orthophosphoric acid and 5.73 g of sodium dihydrogen orthophosphate monohydrate, and dilute to 1000 mL with water. If necessary, adjust the pH to 2.0 using orthophosphoric acid.
PROCEDURE
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) 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 0.0011% w/v of Nevirapine.
(2) 0.054% w/v of nevirapine BPCRS in ethanol (96%). Dilute 1 volume to 50 volumes with dissolution medium.
(3) Dissolve the contents of a vial of nevirapine for peak identification EPCRS in 2 mL of the dissolution medium.
Nevirapine Tablets
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 3.9 mm) packed with end-capped octadecylsilyl silica gel for chromatography (4 μm) (Nova-pak 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 20 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 4 minutes.
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 3.0.
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 75% (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 powdered tablets containing 0.2 g of Nevirapine with 40 mL of acetonitrile and 20 mL of the mobile phase. Dilute to 200 mL with the mobile phase and filter through a 0.45-μm membrane filter.
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase. Dilute 1 volume of this solution to 5 volumes with the mobile phase.
(3) Dissolve the contents of a vial of nevirapine for peak identification EPCRS in 2 mL of the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped amidohexadecylsilyl silica gel for chromatography (5 μm) (Supelcosil LC-ABZ 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 a column temperature of 35°.
(e) Use a detection wavelength of 220 nm.
(f) Inject 20 μL of each solution.
(g) Allow chromatography to proceed for 4 times the retention time of nevirapine.
MOBILE PHASE
15 volumes of acetonitrile and 85 volumes of a 0.288% w/v solution of ammonium dihydrogen orthophosphate previously adjusted to pH 5.0 using dilute sodium hydroxide solution.
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to nevirapine (retention time about 13 minutes) are: impurity B, about 0.7; impurity A, 1.5; impurity C, about 2.8.
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 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 3 times the area of the principal peak in the chromatogram obtained with solution (2) (0.6%).
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
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions in solution A.
Solution A: equal volumes of ethanol and water.
(1) Mix with the aid of ultrasound a quantity of the powdered tablets containing 0.2 g of Nevirapine with 150 mL, and dilute to 200 mL. Mix and centrifuge a portion of the solution. Dilute 1 volume of the supernatant liquid to 50 volumes, filter through a membrane filter (nominal pore size 0.45 μm), and use the filtrate.
(2) 0.002% w/v solution of nevirapine BPCRS.
(3) Dissolve the contents of a vial of nevirapine for peak identification EPCRS in 2 mL.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution 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 3.0.
DETERMINATION OF CONTENT
Calculate the content of nevirapine, C15H14N4O, in the tablets from the chromatograms obtained and using the declared content of C15H14N4O in nevirapine BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Nevirapine.
