Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Non-nucleoside reverse transcriptase inhibitor; antiviral (HIV).
DEFINITION
Nevirapine Prolonged-release Tablets contain Nevirapine. They are formulated so that the active ingredient is released over a period of several hours.
The tablets comply with the requirements stated under Tablets and with the following requirements.
PRODUCTION
A suitable dissolution test is carried out to demonstrate the appropriate release of Nevirapine. The dissolution profile reflects the in vivo performance which in turn is compatible with the dosage schedule recommended by the manufacturer.
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
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 80 mL of
methanol and dilute to 100 mL with methanol. Filter through a 0.45-μm membrane filter and dilute 1 volume of the filtrate to 2 volumes with the mobile phase.
(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
Solution B: Dissolve 2.88 g of ammonium dihydrogen orthophosphate in 1000 mL of water, adjusted to pH 5.0 with 1M sodium hydroxide.
15 volumes of acetonitrile and 85 volumes of solution B.
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to nevirapine (retention time of 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 5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.0%).
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.
(1) Mix with the aid of ultrasound a quantity of the powdered tablets containing 0.2 g of Nevirapine with 120 mL of methanol. Add 40 mL of water and further mix. Dilute to 200 mL with methanol, mix and centrifuge. Dilute 1 volume of the supernatant liquid to 50 volumes with methanol (80%) and filter through a 0.45-μm membrane filter.
(2) 0.002% w/v solution of nevirapine BPCRS in methanol (80%).
(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 × 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 an autosampler temperature of 10°.
(f) Use a detection wavelength of 214 nm.
(g) 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 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.
