Nevirapine Extended-Release Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Nevirapine Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of nevirapine (C₁₅H₁₄N₄O). 

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The retention time of the nevirapine peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Solution A: Acetonitrile and water (15:85)

Solution B: Acetonitrile and water (40:60)

Mobile phase: See Table 1.

Table 1

[NOTE-These gradient elution times are established on an HPLC system with a hold time of approximately 7 min based on the dwell volume of 0.7 mL. Adjust the start of the gradient to be approximately 2 min after the retention time of nevirapine and adjust the remaining gradient accordingly. The hold time (X) can be calculated using the formula: X = (11.2 mL - dwell volume)/flow rate.]

Diluent: Acetonitrile and water (30:70)

Standard solution: 0.5 mg/mL of USP Nevirapine Anhydrous RS in Solution B. Sonicate if necessary to dissolve, before final dilution.

Sample stock solution: Nominally 2 mg/mL of nevirapine prepared as follows. Transfer an appropriate number of Tablets to a suitable volumetric flask. Add 50% of the flask volume of acetonitrile and shake for 30 min. Add 30% of the flask volume of water and continue shaking for another 30 min. Allow it to stand for at least 1 h and dilute with water to volume. Centrifuge a portion and use the supernatant.

Sample solution: Nominally 0.5 mg/mL of nevirapine in Diluent from the Sample stock solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 282 nm. For Identification A, use a diode array detector in the range of 210-400 nm.

Column: 3.9-mm x 15-cm; 5-µm packing L1

Column temperature: 35°

Flow rate: 1.5 mL/min

Injection volume: 25 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of nevirapine (C₁₅H₁₄N₄O) in the portion of Tablets taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of nevirapine from the Sample solution

r_S = peak response of nevirapine from the Standard solution

C_S = concentration of USP Nevirapine Anhydrous RS in the Standard solution (mg/mL)

C_U = nominal concentration of nevirapine in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

4.1.1 Test 1 ▲(RB 1-May-2018)

Medium: 0.04 M sodium phosphate buffer pH 6.8 containing 2% sodium dodecyl sulfate prepared as follows. Dissolve 6.0 g of monobasic sodium phosphate in 800 mL of water and adjust with a 50% sodium hydroxide solution to a pH of 6.8. Add 20 g of sodium dodecyl sulfate and dilute with water to 1000 mL; 900 mL.

Apparatus 1: 75 rpm

Times

For Tablets labeled to contain 100 mg: 1, 5, and 12 h

For Tablets labeled to contain 400 mg: 2, 8, and 20 h

Mobile phase: Acetonitrile and water (18:82)

Standard solution: (L/900) mg/mL of USP Nevirapine Anhydrous RS in Medium, where L is the label claim in mg/Tablet prepared as follows. Transfer a weighed quantity of USP Nevirapine Anhydrous RS to a suitable volumetric flask and add ethyl alcohol to fill 12% of the flask volume. Sonicate for 15 min or until dissolved. Allow to cool to room temperature and dilute with Medium to volume.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 282 nm

Column: 3.9-mm x 15-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: About 1.6 times the retention time of nevirapine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of nevirapine (C₁₅H₁₄N₄O) dissolved in the portion of the sample withdrawn at each time point (1) (mg/mL):

                         C_i = (r_U/r_S) × C_S

r_U = peak response of nevirapine from the Sample solution

r_S = peak response of nevirapine from the Standard solution

C_S = concentration of USP Nevirapine Anhydrous RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of nevirapine (C₁₅H₁₄N₄O) dissolved at each time point (i):

                         Result₁ = C₁ x V x (1/L) x 100

                         Result₂ = {[C₂ x (V - V_S)] + (C₁ x V_S)) x (1/L) x 100

                         Result₃ = ((C₃ x [V - (2 x V_S)] + [(C₂ + C₁) x V_S) x (1/L) x 100

C_i = concentration of nevirapine in the portion of sample withdrawn at the time point (1)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point (mL)

Tolerances

For Tablets labeled to contain 100 mg: See Table 2.

Table 2

The percentages of the labeled amount of nevirapine (C₁₅H₁₄N₄O) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

For Tablets labeled to contain 400 mg: See Table 3.

Table 3

The percentages of the labeled amount of nevirapine (C₁₅H₁₄N₄O) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

4.1.2 Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.04 M sodium phosphate buffer pH 6.8 containing 2% sodium dodecyl sulfate prepared as follows. Dissolve 6.24 g of sodium dihydrogen phosphate dihydrate and 0.89 g of sodium hydroxide in 1000 mL of water. Adjust with 0.2 N hydrochloric acid or with 0.2 N sodium hydroxide solution to a pH of 6.8. Add 20 g of sodium dodecyl sulfate and sonicate for about 30 min to dissolve; 900 mL.

Apparatus 1: 75 rpm

Times

For Tablets labeled to contain 100 mg: 1, 4, and 8 h

For Tablets labeled to contain 400 mg: 1, 6, and 20 h

Solution A: 0.2% (v/v) of triethylamine in water. Adjust with phosphoric acid to a pH of 5.0.

Mobile phase: Acetonitrile and Solution A (30:70)

Standard stock solution: 0.9 mg/mL of USP Nevirapine Anhydrous RS in methanol prepared as follows. Transfer a weighed quantity of USP Nevirapine Anhydrous RS to a suitable volumetric flask, add methanol to fill 60% of the flask volume, and sonicate to dissolve. Dilute with methanol to volume.

Standard solution: 0.036 mg/mL of USP Nevirapine Anhydrous RS in Medium from Standard stock solution. Pass through a suitable filter of 0.45-µm pore size.

Sample solution: Dilute a filtered portion of the solution under test with Medium to a concentration similar to that of the Standard solution.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 285 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Column temperature: 25°

Flow rate: 1.2 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of nevirapine (C₁₅H₁₄N₄O) dissolved in the portion of the sample withdrawn at each time point (i) (mg/mL):

                         C_i = (r_U/r_S) × C_S × D

r_U = peak response of nevirapine from the Sample solution

r_S = peak response of nevirapine from the Standard solution

C_S = concentration of USP Nevirapine Anhydrous RS in the Standard solution (mg/mL)

D = dilution factor for the Sample solution

Calculate the percentage of the labeled amount of nevirapine (C₁₅H₁₄N₄O) dissolved at each time point (i):

                         Result₁ = C₁ x V x (1/L) x 100

                         Result₂ = {[C₂ x (V - V_S)] + (C₁ x V_S)) x (1/L) x 100

                         Result₃ = ((C₃ x [V - (2 x V_S)] + [(C₂ + C₁) x V_S) x (1/L) x 100

C_i = concentration of nevirapine in the portion of sample withdrawn at the time point (1)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point and replaced with Medium (mL)

Tolerances

For Tablets labeled to contain 100 mg: See Table 4.

Table 4

The percentages of the labeled amount of nevirapine (C₁₅H₁₄N₄O) dissolved at the times specified conform to Dissolution (711). Acceptance Table 2.

For Tablets labeled to contain 400 mg: See Table 5.

Table 5

The percentages of the labeled amount of nevirapine (C₁₅H₁₄N₄O) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2 _{▲(RB 1-May-2018)}

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirement

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 0.5 mg/mL of USP Nevirapine Anhydrous RS and 0.005 mg/mL of USP Nevirapine Related Compound A RS in Solution B. Sonicate if necessary to dissolve, before final dilution.

Standard stock solution: Use the Standard solution from the Assay.

Standard solution: 0.0005 mg/mL of USP Nevirapine Anhydrous RS in Solution B from the Standard stock solution

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 4.0 between the nevirapine and nevirapine related compound A peaks, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of any individual impurity in the portion of Tablets taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any individual impurity from the Sample solution 

'r_S = peak response of nevirapine from the Standard solution

C_S = concentration of USP Nevirapine Anhydrous RS in the Standard solution (mg/mL)

C_U = nominal concentration of nevirapine in the Sample solution (mg/mL)

Acceptance criteria: See Table ^▲6 _{▲(RB 1-May-2018)} Disregard any impurity peak less than 0.1%.

Table ^▲6 _{▲(RB 1-May-2018)}

^a 5,11-Dihydro-4-methyl-6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one.

^b Process impurity included in the table for identification only. Process impurities are controlled in the drug substance, and are not to be reported or included in the total impurities for the drug product.

^c 5,11-Dihydro-6H-11-propyl-4-methyl-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers. Store at controlled room temperature.

Add the following:

^▲ LABELING: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used._{▲ (RB 1-May-2018)}

USP REFERENCE STANDARDS (11)

USP Neviragine Anhydrous RS

USP Neviranine Related Compound A RS

5,11-Dihydro-6H-11-ethyl-4-methyl-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one.

C₁₄H₁₄N₄O           254.29