Verapamil Hydrochloride Extended-Release Tablets
If you find any inaccurate information, please let us know by providing your feedback here
This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition
Issued and maintained by the United States Pharmacopeial Convention (USP)
1 DEFINITION
Verapamil Hydrochloride Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl).
2 IDENTIFICATION
A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
B. The UV spectrum of the major peak of the Diluted sample solution corresponds to that of the Diluted standard solution, as obtained in the Assay.
3 ASSAY
3.1 Procedure
Buffer: To 0.82 g of sodium acetate, add 33 mL of glacial acetic acid and dilute with water to 1 L.
Mobile phase: Acetonitrile, 2-aminoheptane, and Buffer (60:1:140)
System suitability solution: 2.5 mg/mL of USP Verapamil Hydrochloride RS and 2.0 mg/mL of USP Verapamil Related Compound B RS in Mobile phase
Standard solution: 1.2 mg/mL of USP Verapamil Hydrochloride RS in Mobile phase
Diluted standard solution: 0.6 mg/mL of USP Verapamil Hydrochloride RS in Mobile phase from the Standard solution
Sample solution: Nominally 1.2 mg/mL of verapamil hydrochloride from Tablets prepared as follows. Transfer an amount equivalent to 240 mg of verapamil hydrochloride, from NLT 20 powdered Tablets, to a 200-mL volumetric flask, and add about 160 mL of Mobile phase. Sonicate for 15 min, stir for 15 min, dilute with Mobile phase to volume, and mix. Centrifuge a portion for 20 min, and use the supernatant.
Diluted sample solution: Nominally 0.6 mg/mL of verapamil hydrochloride in Mobile phase from the Sample solution
Chromatographic system
- (See Chromatography 〈621〉, System Suitability.)
- Mode: LC
- Detector: UV 278 nm. For Identification B, use a diode array detector in the range of 200–400 nm.
- Column: 4.6-mm × 15-cm; 5-µm packing L1
- Flow rate: 1 mL/min
- Injection volume: 10 µL
- Run time: NLT 3 times the retention time of verapamil
System suitability
- Samples: System suitability solution and Standard solution
- [Note-The relative retention times for verapamil related compound B and verapamil are 0.85 and 1.0, respectively.]
- Suitability requirements
- Resolution: NLT 1.5 between verapamil and verapamil related compound B, System suitability solution
- Relative standard deviation: NMT 2.0%, Standard solution
Analysis
Samples: Standard solution, Diluted standard solution, Sample solution, and Diluted sample solution
[Note-The Diluted standard solution and Diluted sample solution are used for Identification B.]
Calculate the percentage of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) in the portion of Tablets taken:
Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100
rᵤ = peak response of verapamil from the Sample solution
rₛ = peak response of verapamil from the Standard solution
Cₛ = concentration of USP Verapamil Hydrochloride RS in the Standard solution (mg/mL)
Cᵤ = nominal concentration of verapamil hydrochloride in the Sample solution (mg/mL)
Acceptance criteria: 90.0%–110.0%
4 PERFORMANCE TESTS
4.1 Dissolution 〈711〉
4.1.1 Test 1 If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 1. Proceed as directed in Dissolution 〈711〉, Procedure, Apparatus 1 and Apparatus 2, Delayed-Release Dosage Forms, Method B Procedure.
Acid stage medium: Using 900 mL of simulated gastric fluid TS (without enzyme), conduct this stage of the test for 1 h.
Buffer stage medium: Using 900 mL of simulated intestinal fluid TS (without enzyme), conduct this stage of the test for 7 h.
Apparatus 2: 50 rpm
Times
- Acid stage: 1 h
- Buffer stage: 2, 3.5, 5, and 8 h
Standard solution: USP Verapamil Hydrochloride RS in 0.01 N hydrochloric acid
Sample solution: Pass portions of the solution under test through a suitable filter. Dilute with medium as necessary.
Blank solution: 0.01 N hydrochloric acid
Analysis: Wrap each Tablet in a wire helix to prevent the Tablets from floating. After 1 h in the Acid stage medium, withdraw a specimen for analysis, and carefully transfer the dosage form, including the wire helix, to a vessel containing the Buffer stage medium, which has been previously warmed to 37 ± 0.5°. At each time interval, pass a portion of the solution under test through a suitable glass microfiber filter paper. Dilute, if necessary, the filtered portions of the solutions under test with water at the 1-h interval and with 0.1 N hydrochloric acid at the 2-, 3.5-, 5-, and 8-h intervals. Determine the percentage of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) dissolved.
[Note-Use only filters that have been shown not to absorb verapamil.]
Detector: UV 278 nm
Tolerances: See Table 1 and Table 2.
Table 1. For Products Labeled to Contain 180 or 240 mg
| Time (h) | Amount Dissolved (%) |
| 1 | 7–15 |
| 2 | 16–30 |
| 3.5 | 31–50 |
| 5 | 51–75 |
| 8 | NLT 85 |
Table 2. For Products Labeled to Contain 120 mg
| Time (h) | Amount Dissolved (%) |
| 1 | 10–21 |
| 2 | 18–33 |
| 3.5 | 35–60 |
| 5 | 50–82 |
| 8 | NLT 85 |
The percentages of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) 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. Proceed as directed for Test 1, except that in the Analysis, the Tablet is not required to be wrapped in a wire helix.
Tolerances: See Table 3, Table 4, and Table 5.
Table 3. For Products Labeled to Contain 240 mg
| Time (h) | Amount Dissolved (%) |
| 1 | 8–20 |
| 2 | 15–35 |
| 3.5 | 35–65 |
| 5 | 55–85 |
| 8 | NLT 80 |
Table 4. For Products Labeled to Contain 180 mg
| Time (h) | Amount Dissolved (%) |
| 1 | 10–25 |
| 2 | 20–40 |
| 3.5 | 40–75 |
| 8 | NLT 80 |
Table 5. For Products Labeled to Contain 120 mg
| Time (h) | Amount Dissolved (%) |
| 1 | 10–25 |
| 2 | 20–40 |
| 3.5 | 35–70 |
| 5 | 55–85 |
| 8 | NLT 80 |
The percentages of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
4.1.3 Test 3 If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3. Proceed as directed for Test 1.
Tolerances: See Table 6.
Table 6
| Time (h) | Amount Dissolved (%) |
| 1 | 8–20 |
| 2 | 15–35 |
| 3.5 | 27–57 |
| 5 | 45–75 |
| 8 | NLT 80 |
The percentages of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
4.1.4 Test 4 If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.
Medium: Simulated intestinal fluid TS (without enzyme); 50 mL
Apparatus 7: 20 cycles/min (see Drug Release 〈724〉)
Detector: UV 278 nm
Standard solution: USP Verapamil Hydrochloride RS in Medium
Analysis: Scrape about 2 mm × 2 mm of the coating from the side edge of the Tablet under test. Glue the system to a plastic rod sample holder at the area where the color has been removed. Attach each plastic sample holder to an arm of the apparatus, which reciprocates at an amplitude of about 2 cm and 15–30 cycles/min. The Tablet is continuously immersed in tubes containing 50 mL of Medium at 37°. At the end of each specified test interval, the systems are transferred to the next row of new test tubes containing 50 mL of fresh Medium. Remove the tubes after the last test interval, and allow them to cool to room temperature. Add 2.0 mL of 1.0 M phosphoric acid to each tube, and dilute with water to 50 mL. Stir and mix each tube thoroughly. Determine the percentages of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) for the filtered portions of the solution under test, suitably diluted with Medium.
Tolerances: See Table 7.
Table 7
| Time (h) | Amount Dissolved (%) |
| 3 | NMT 10 |
| 6 | 20–50 |
| 9 | 52.5–82.5 |
| 14 | NLT 85 |
The percentages of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
4.1.5 Test 5 If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.
Phosphate buffer: Dissolve 6.8 g of monobasic potassium phosphate in 250 mL of water. Add 190 mL of 0.2 N sodium hydroxide in 400 mL of water, adjust with 0.2 N sodium hydroxide to a pH of 7.5 ± 0.1, and dilute with water to 1000 mL.
Medium: Phosphate buffer; 900 mL
Apparatus 2: 50 rpm
Detector: UV 278 nm
Standard solution: USP Verapamil Hydrochloride RS in Medium
Sample solution: Pass portions of the solution under test through a suitable filter. Dilute with Medium as necessary.
Analysis: Determine the percentage of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) dissolved.
Tolerances: See Table 8.
Table 8
| Time (h) | Amount Dissolved (%) |
| 1 | 2–12 |
| 2 | 10–25 |
| 4 | 25–50 |
| 8 | NLT 80 |
The percentages of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
4.1.6 Test 6: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 6.
Acid stage medium, Buffer stage medium, Apparatus 2, Times, and Detector: Proceed as directed for Test 1.
Standard solution: 0.04 mg/mL of USP Verapamil Hydrochloride RS in 0.01 N hydrochloric acid
Sample solution: Pass portions of the solution under test through a suitable filter. Dilute with 0.1 N hydrochloric acid to prepare a sample of concentration similar to that of the Standard solution.
Analysis
Samples: Standard solution and Sample solution
Proceed as directed for Test 1.
Calculate the concentration (Cᵢ) of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) dissolved in medium (mg/mL) at each time point (i):
Cᵢ = (Aᵤ/Aₛ) × Cₛ × D
Aᵤ = absorbance of verapamil from the Sample solution
Aₛ = absorbance of verapamil from the Standard solution
Cₛ = concentration of USP Verapamil Hydrochloride RS in the Standard solution (mg/mL)
D = dilution factor
Calculate the percentage of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) dissolved (Qi), at each time point (i):
Result₁ = (C₁ × V) × (1/L) × 100
Result₂ = {[C₂ × (V − Vₛ)] + (C₁ × Vₛ)} × (1/L) × 100
Result₃ = ({C₃ × [V − (2 × Vₛ)]} + [(C₂ + C₁) × Vₛ]) × (1/L) × 100
Result₄ = ({C₄ × [V − (3 × Vₛ)]} + [(C₃ + C₂ + C₁) × Vₛ]) × (1/L) × 100
Result₅ = ({C₅ × [V − (4 × Vₛ)]} + [(C₄ + C₃ + C₂ + C₁) × Vₛ]) × (1/L) × 100
Cᵢ = concentration of verapamil hydrochloride in the portion of the sample withdrawn at time point i (mg/mL)
V = volume of Medium, 900 mL
L = label claim (mg/Tablet)
Vₛ = volume of the Sample solution withdrawn at each time point from the medium in the Buffer stage (mL)
Tolerances: See Table 9.
Table 9
| Time Point (i) | Time (h) | Amount Dissolved (%) | ||
| Tablet Strength-240 mg | Tablet Strength-180 mg | Tablet Strength-120 mg | ||
| 1 | 1 | 10–25 | 10–25 | 15–30 |
| 2 | 2 | 25–45 | 27–47 | 35–55 |
| 3 | 3.5 | 50–75 | 55–80 | 60–85 |
| 4 | 5 | 70–90 | NLT 75 | NLT 80 |
| 5 | 8 | NLT 85 | NLT 85 | NLT 85 |
The percentages of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
4.1.7 Test 7: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 7.
Acid stage medium: Simulated gastric fluid TS (without enzyme); 900 mL
Buffer stage medium: Simulated intestinal fluid TS (without enzyme); 900 mL
Apparatus 2: 50 rpm, with a sinker (see Dissolution 〈711〉, Figure 2a)
Times
- Acid stage: 1 h
- Buffer stage: 2, 3.5, 5, and 8 h
Diluent: 0.01 N hydrochloric acid
Dilute phosphoric acid: Dilute 5.0 mL of phosphoric acid with water to 50 mL.
Buffer: 1.74 g/L of dibasic potassium phosphate in water. Adjust to a pH of 7.5 using Dilute phosphoric acid.
Mobile phase: Acetonitrile and Buffer (650:350)
Standard solution: Prepare the corresponding USP Verapamil Hydrochloride RS solutions in Diluent as directed in Table 10. Pass through a suitable membrane filter of 0.45-µm pore size.
Table 10
| Tablet Strength (mg) | Concentration of USP Verapamil Hydrochloride RS (µg/mL) |
| 240 | 270 |
| 120 | 135 |
| 180 | 203 |
Sample solutions: Pass a portion of the solution under test at each time point through a suitable filter of 1-µm pore size, and use the filtrate.
Chromatographic system
- (See Chromatography 〈621〉, System Suitability.)
- Mode: LC
- Detector: UV 278 nm
- Column: 4.6-mm × 25-cm; 5-µm packing L7
- Column temperature: 30°
- Flow rate: 1.5 mL/min
- Injection volume: 10 µL
- Run time: NLT 1.4 times the retention time of verapamil
System suitability
- Sample: Standard solution
- Suitability requirements
- Tailing factor: NMT 2.0
- Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solution and Sample solutions
After 1 h in the Acid stage medium, withdraw 10 mL of the solution under test. Carefully transfer the dosage form including the sinker to a vessel containing the Buffer stage medium, previously warmed to 37 ± 0.5°.
Calculate the percentage of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) dissolved in the Acid stage medium:
Result = (rᵤ/rₛ) × Cₛ × V × (1/L) × 100
rᵤ = peak response of verapamil from the Sample solutions
rₛ = peak response of verapamil from the Standard solution
Cₛ = concentration of USP Verapamil Hydrochloride RS in the Standard solution (mg/mL)
V = volume of Acid stage medium, 900 mL
L = label claim (mg/Tablet)
Calculate the concentration (Cᵢ) of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) in the sample withdrawn from the vessel at each Buffer stage time point (i):
Resulti = (rᵤ/rₛ) × Cₛ
rᵤ = peak response of verapamil from the Sample solution at each time point (i)
rₛ = peak response of verapamil from the Standard solution
Cₛ = concentration of USP Verapamil Hydrochloride RS in the Standard solution (mg/mL)
Calculate the percentage of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) dissolved at each time point (i):
Result₁ = C₁ × V × (1/L) × 100
Result₂ = {[C₂ × (V − Vₛ)] + (C₁ × Vₛ)} × (1/L) × 100
Result₃ = ({C₃ × [V − (2 × Vₛ)]} + [(C₂ + C₁) × Vₛ]) × (1/L) × 100
Result₄ = ({C₄ × [V − (3 × Vₛ)]} + [(C₃ + C₂ + C₁) × Vₛ]) × (1/L) × 100
Cᵢ = concentration of verapamil hydrochloride in the Sample solution at the specified time point i (mg/mL)
V = volume of Buffer stage medium, 900 mL
L = label claim (mg/Tablet)
Vₛ = volume of the Sample solution withdrawn at each time point (mL)
Tolerances: See Table 11.
Table 11
| Time Point (i) | Time (h) | Amount Dissolved (%) | ||
| Tablet Strength-240 mg | Tablet Strength-180 mg | Tablet Strength-120 mg | ||
| 1 | 1 | 7–20 | 7–20 | 10–21 |
| 2 | 2 | 15–30 | 15–30 | 18–33 |
| 3 | 3.5 | 31–60 | 31–60 | 30–55 |
| 4 | 5 | 55–85 | 55–85 | 50–82 |
| 5 | 8 | NLT 85 | NLT 85 | NLT 85 |
The percentages of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
4.2 Uniformity of Dosage Units 〈905〉
Meet the requirements
5 IMPURITIES
5.1 Organic Impurities
Buffer, Mobile phase, System suitability solution, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.
Analysis
Sample: Sample solution
Calculate the percentage of each unspecified degradation product in the portion of Tablets taken:
Result = (rU/rT) × 100
rU = peak response for each unspecified degradation product from the Sample solution
rT = sum of all peak responses from the Sample solution
Acceptance criteria: See Table 12.
Table 12
| Name | Relative Retention Time | Acceptance Criteria, NMT (%) |
| Verapamil related compound Bᵃ | 0.85 | - |
| Verapamil | 1.0 | - |
| Any unspecified degradation product | - | 0.5 |
| Total degradation products | - | 1.0 |
ᵃ For resolution measurement only. Do not include it in the total.
6 ADDITIONAL REQUIREMENTS
Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature.
Labeling: The labeling indicates the Dissolution test with which the product complies.
USP Reference Standards 〈11〉
USP Verapamil Hydrochloride RS
USP Verapamil Related Compound B RS
Benzeneacetonitrile, 4-[(3,4-Dimethoxyphenethyl)(methyl)amino]-2-(3,4-dimethoxyphenyl)-2-isopropylbutanenitrile hydrochloride.
C₂₆H₃₆N₂O₄ · HCl 477.04
