Acetaminophen Extended-Release Tablets
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Tóm tắt nội dung
- DEFINITION
- IDENTIFICATION
- ASSAY
- PERFORMANCE TESTS
- DISSOLUTION (711)
- Test 1
- Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
- Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
- Test 4: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.
- UNIFORMITY OF DOSAGE UNITS (905)
- IMPURITIES
- ADDITIONAL REQUIREMENTS
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
Acetaminophen Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of acetaminophen (C8H9NO2).
2 IDENTIFICATION
A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K
Sample: A portion of powdered Tablets
Acceptance criteria: Meet the requirements
B. The retention time of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
3 ASSAY
3.1 PROCEDURE
Solution A: Phosphoric acid and water (1:9)
Mobile phase: Methanol, Solution A, and water (300:1:700)
Standard solution: 0.65 mg/mL of USP Acetaminophen RS in Mobile phase. Prepare by first dissolving in methanol, and then diluting with Mobile phase to volume.
Sample stock solution: Transfer 10 Tablets to a 250-mL volumetric flask containing 50 mL of water and a magnetic stir bar. Stir for at least 30 min or until the coating has dissolved. Add 150 mL of methanol, and stir for 45 min. Tablet cores should be disintegrated at least 15 min before ending the stirring. Remove the magnetic stir bar, and rinse into the flask with methanol. Dilute with methanol to volume, and centrifuge. Use the clear supernatant.
Sample solution: Dilute 5 mL of the Sample stock solution with Mobile phase to 200 mL.
3.2 Chromatographic system
(See Chromatography (621), System Suitability.)
Mode: LC
Detector: UV 295 nm
Column: 3.9-mm × 15-cm; packing 11
Flow rate: 2.0 mL/min
Injection volume: 20 µL
3.3 System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 3.0
Relative standard deviation: NMT 2.0%
3.4 Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of acetaminophen (C8H9NO2) in the portion of Tablets taken:
Result = (rU/rS) x (CS/CU) × 100
rU = peak response from the Sample solution
rS = peak response from the Standard solution
CS = concentration of USP Acetaminophen RS in the Standard solution (mg/mL)
CU = nominal concentration of acetaminophen 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
Medium: Simulated gastric fluid TS (without enzyme); 900 mL
Apparatus 2: 50 rpm
Times: 15 min, 1 h, and 3 h
Standard solution: A known concentration of USP Acetaminophen RS in Medium
Sample solution: A filtered portion of the solution under test, suitably diluted with Medium to obtain a concentration similar to that of the Standard solution
4.1.1.1 Instrumental conditions
Mode: UV
Analytical wavelength: 280 nm
4.1.1.2 Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of acetaminophen (CH,NO₂) dissolved.
Tolerances: See Table 1.
| Time | Amount Dissolve |
| 15 min | 45%-65% |
| 4 h | 60%-85% |
| 3 h | NLT 85% |
The percentages of the labeled amount of acetaminophen (C8H9NO2) dissolved at the times specified conform to Acceptance Table 2 in (711).
4.1.1.3 For gelatin-coated Tablets
Medium, Apparatus, Standard solution, Sample solution, Instrumental conditions, and Analysis: Proceed as directed in Test 1.
Times: 30 min, 90 min, and 4 h
Tolerances: See Table 2.
| Time | Amount Dissolve |
| 30 min | 40%-60% |
| 90 min | 55%-85% |
| 4 h | NLT 80% |
The percentages of the labeled amount of acetaminophen (C8H9NO2) dissolved at the times specified conform to Acceptance Table 2 in (711).
4.1.2 Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium, Apparatus, Standard solution, Sample solution, Instrumental conditions, and Analysis: Proceed as directed in Test 1.
Times: 15 min, 1 h, and 3 h
Tolerances: See Table 3.
| Time | Amount Dissolve |
| 15 min | 40%-60% |
| 1 h | 55%-75% |
| 3 h | NLT 80% |
The percentages of the labeled amount of acetaminophen (C8H9NO2) dissolved at the times specified conform to Acceptance Table 2 in (711).
4.1.3 Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium: Simulated gastric fluid TS (without enzyme); 900 mL
Apparatus 2: 50 rpm
Times: 30, 90, and 240 min
Standard stock solution: 1.44 mg/mL of USP Acetaminophen RS in methanol. Sonicate to dissolve, if necessary.
Standard solution: (L/9000) mg/mL of USP Acetaminophen RS from Standard stock solution in Medium, where L is the label claim in mg/Tablet
Sample solution: At the times specified, withdraw 10 mL of the solution under test and replace with 10 mL of Medium. Pass the solution under test through a suitable filter of 0.45-µm pore size. Dilute with Medium to a concentration that is similar to that of the Standard solution.
4.1.3.1 Instrumental conditions
Mode: UV
Analytical wavelength: 280 nm
4.1.3.2 Analysis
Samples: Standard solution and Sample solution
Calculate the concentration (C) of acetaminophen (C8H9NO2) in the sample withdrawn from the vessel at each time point (i):
Resulti = (AU/AS) x CS x D
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
CS = concentration of USP Acetaminophen RS in the Standard solution (mg/mL)
D = dilution factor for the Sample solution
Calculate the percentage of the labeled amount of acetaminophen (C8H9NO2) dissolved at each time point (1):
Result1 = C1 x V x (1/L) x 100
Result2 = [(C2 x V) + (C1 x V)] × (1/L) x 100
Result3 = {(C3 x V) + [(C2 + C1) x VS) x (1/L) x 100
Ci = concentration of acetaminophen in the portion of 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 and replaced with Medium (mL)
Tolerances: See Table 4.
| Time Point (i) | Time (min) | Amount Dissolved (%) |
| 1 | 30 | 45–65 |
| 2 | 90 | 65–85 |
| 3 | 240 | NLT 85 |
The percentages of the labeled amount of acetaminophen (C8H9NO2) 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: Gastric fluid, simulated,TIS (without enzyme); deaerated, 900 mL
Apparatus 2: 50 rpm
Times: 15, 60, and 180 min
Mobile phase: Methanol, glacial acetic acid, and water (20:1:79)
Standard solution: 0.72 mg/mL of USP Acetaminophen RS prepared as follows. Transfer an appropriate quantity of USP Acetaminophen RS to a suitable volumetric flask, add 2% of the flask volume of methanol, and if necessary, sonicate to dissolve. Dilute with Medium to volume.
Sample solution: At the times specified, pass a portion of the solution under test through a suitable filter, discarding an appropriate volume of filtrate so that a consistent result can be obtained.
4.1.4.1 Chromatographic system
(See Chromatography (621), System Suitability.)
Mode: LC
Detector: UV 280 nm
Column: 4.6-mm x 7.5-cm; 3.5-µm packing 17
Flow rate: 1.5 mL/min
Injection volume: 5 µL
Run time: NLT 1.7 times of the retention time of acetaminophen
4.1.4.2 System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2.5
Relative standard deviation: NMT 2.0%
4.1.4.3 Analysis
Samples: Standard solution and Sample solution
Calculate the concentration (C) of acetaminophen (C8H9NO2) in the sample withdrawn from the vessel at each time point (i):
Resulti = (rU/rS) x CS
rU = peak response of acetaminophen from the Sample solution
rS = peak response of acetaminophen from the Standard solution
CS = concentration of USP Acetaminophen RS in the Standard solution (mg/mL)
Calculate the percentage of the labeled amount of acetaminophen (C8H9NO2) dissolved at each time point (i):
Result1 = C1 x V x (1/L) x 100
Result2 = {[C2 x (V-VS)] + (C1 x V)} × (1/L) x 100
Result3 = ({C3 x [V- (2 x VS)]} + [(C2 + C1) x VS] x (1/L) x 100
Ci = concentration of acetaminophen in the portion of 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 (mL)
Tolerances: See Table 5.
| Time Point (i) | Time (min) | Amount Dissolved (%) |
| 1 | 15 | 45–65 |
| 2 | 60 | 65–80 |
| 3 | 180 | NLT 80 |
The percentages of the labeled amount of acetaminophen (C8H9NO2) dissolved at the times specified conform to Dissolution (711). Acceptance Table 2 (RB 1-Dec-2023)
4.2 UNIFORMITY OF DOSAGE UNITS (905)
Meet the requirements
5 IMPURITIES
4-AMINOPHENOL IN ACETAMINOPHEN-CONTAINING DRUG PRODUCTS (227): Meet the requirements
6 ADDITIONAL REQUIREMENTS
PACKAGING AND STORAGE: Preserve in tight containers.
Labeling: Where the Tablets are gelatin-coated, the label so states. When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
USP Reference Standards (11)
USP Acetaminophen RS
