Alfuzosin Hydrochloride 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

Alfuzosin Hydrochloride Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄ · HCl).

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 197K.

Sample: Grind 4 Tablets, and add 20 mL of water. [Note—When analyzing multi-layer Tablets, isolate the layer containing alfuzosin hydrochloride using a suitable tool.] Add 20 mL of strong ammonia solution. Extract with 20 mL of methylene chloride, and separate the organic layer. Repeat the extraction successively with 20 mL, then with 10 mL of methylene chloride. Wash the combined organic layers with 20 mL of water. Dry the organic solution using a phase separation lter. Take 2.0 mL of the dried organic solution, and mix with 200 mg of nely ground potassium bromide. Evaporate the methylene chloride at 60°, then at 105° for 30 min. Make a disk. Alternatively, evaporate methylene chloride from the dried organic solution at 60°, then at 105° for 30 min. Perform the IR spectrum.

Acceptance criteria: The maxima of the spectrum obtained from the Sample correspond in position and relative intensity to those obtained from USP Alfuzosin Hydrochloride RS, treated in the same manner as the Sample, beginning with “add 20 mL of water.” • B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Solution A: 5.0 mL of perchloric acid in 900 mL of water. Adjust with 2 M sodium hydroxide to a pH of 3.5, and dilute with water to 1000 mL. Mobile phase: Acetonitrile, tetrahydrofuran, and Solution A (20:1:80)

Diluent: 0.01 N hydrochloric acid

Standard stock solution: 0.15 mg/mL of USP Alfuzosin Hydrochloride RS in methanol

Standard solution: 0.03 mg/mL of USP Alfuzosin Hydrochloride RS in Diluent from the Standard stock solution

Sample stock solution: Place a suitable number of Tablets into a suitable volumetric ask to obtain a solution having a concentration of 0.16 mg/mL of alfuzosin hydrochloride. Add 80% of the ask volume of methanol, and stir for at least 1 h using a magnetic stirrer. Add 10% of the ask volume of Diluent, mix, and allow it to cool to room temperature. Dilute the resulting suspension with methanol to volume, stir, and allow to settle for 30 min.

Sample solution: 0.03 mg/mL of alfuzosin hydrochloride in Diluent from the Sample stock solution supernatant. Pass through a suitable lter. Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

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

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: 0.8–1.5 for alfuzosin

Relative standard deviation: NMT 2.0%

3.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄· HCl) in the portion of Tablets taken: 

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Alfuzosin Hydrochloride RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Test 1

Medium: 0.01 N hydrochloric acid; 500 mL

Apparatus 2: 100 rpm, with Tablet holder (see Figure 1)

Times: 1, 6, 12, and 20 h

Sample solution: Pass a portion of the solution under test through a suitable lter.

Standard solution: (L/500) mg/mL of USP Alfuzosin Hydrochloride RS in Medium, where L is the Tablet label claim in mg Detector: UV 330 nm

Blank: Medium

Path length: 1 cm

Tolerances: See Table 1.

Table 1

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

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 2: 100 rpm

Times: 1, 3, 12, and 24 h

Buffer: Dilute 5.0 mL of perchloric acid in 900 mL of water, adjust with diluted sodium hydroxide (0.1 g/mL) to a pH of 3.5 ± 0.5, and dilute with water to 1 L.

Mobile phase: Acetonitrile and Buffer (25:75)

Standard stock solution: 0.28 mg/mL of USP Alfuzosin Hydrochloride RS, prepared as follows. In a 200-mL volumetric ask dissolve 55.5 mg of USP Alfuzosin Hydrochloride RS in 5 mL of methanol, sonicate to dissolve, and dilute with Medium to volume. Standard solution: 0.011 mg/mL of USP Alfuzosin Hydrochloride RS in Medium from the Standard stock solution Sample solution: Pass a portion of the solution under test through a suitable lter. Replace the portion of solution withdrawn with an equal volume of Medium.

4.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 244 nm

Column: 4.6-mm × 15-cm; 5-µm packing L7

Column temperature: 30°

Flow rate: 1.2 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Column eciency: NLT 3000 theoretical plates

Relative standard deviation: NMT 2.0%

4.3 Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C ) of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄ · HCl) in the sample withdrawn from the vessel at each time point (i):

Result_i = (r_U /r_S ) × C_S

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Alfuzosin Hydrochloride RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄· HCl) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = [(C₂ × V) + (C₁ × V_S )] × (1/L) × 100

Result₃ = {(C₃ × V) + [(C₂ + C₁ ) × V_S ]} × (1/L) × 100

Result₄ = {(C₄ × V) + [(C₃ + C₂ + C₁ ) × V_S ]} × (1/L) × 100

C_i = concentration of alfuzosin hydrochloride in the portion of sample withdrawn at the specied time point (mg/mL) 

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: See Table 2.

The percentages of the labeled amount of alfuzosin hydrochloride dissolved at the times specied conform to Dissolution 〈711〉, Acceptance Table 2.

Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Medium: 0.25% sodium dodecyl sulfate in 0.05 M sodium phosphate buffer, pH 6.8 (2.5 g/L of sodium dodecyl sulfate, 6.9 g/L of monobasic sodium phosphate monohydrate, and 0.83 g/L of sodium hydroxide in water previously degassed with helium. Adjust with either phosphoric acid or 1 N sodium hydroxide to a pH of 6.8 ± 0.05); 900 mL

Apparatus 1: 100 rpm

Times: 1, 6, 12, and 24 h

Standard stock solution: 1.1 mg/mL of USP Alfuzosin Hydrochloride RS in methanol

Standard solution: 0.011 mg/mL of USP Alfuzosin Hydrochloride RS in Medium from the Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable lter.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV-Vis

Analytical wavelength: 331 nm, background correction at 490 nm

Blank: Medium

Cell: 1.0 cm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄· HCl) dissolved at each time point (i):

Resulti = (A_U /A_S ) × C_S × V × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Alfuzosin Hydrochloride RS in the Standard solution (mg/mL)

V = volume of Medium (mL)

L = label claim (mg/Tablet)

Tolerances: See Table 3.

Table 3

The percentages of the labeled amount of alfuzosin hydrochloride dissolved at the times specied conform to Dissolution 〈711〉, Acceptance Table 2.

Test 4: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 2: 100 rpm

Times: 1, 6, 12, and 20 h

Standard solution: 0.01 mg/mL of USP Alfuzosin Hydrochloride RS in Medium

Sample solution: Centrifuge a portion of the solution under test.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 245 nm

Blank: Medium

Path length: 0.2 cm Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄· HCl) in the sample withdrawn from the vessel at each time

point (i):

Resulti = (A_U/A_S ) × C_S

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Alfuzosin Hydrochloride RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄ · HCl) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = [(C₂ × V) + (C₁ × V_S )] × (1/L) × 100

Result₃ = {(C₃ × V) + [(C₂ + C₁ ) × VS ]} × (1/L) × 100

Result₄ = {(C₄ × V) + [(C₃ + C₂ + C₁ ) × VS ]} × (1/L) × 100

C_i = concentration of alfuzosin hydrochloride in the portion of sample withdrawn at the specied time point (mg/mL) i

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: See Table 4.

Table 4

The percentages of the labeled amount of alfuzosin hydrochloride dissolved at the times specied conform to Dissolution 〈711〉, Acceptance Table 2.

Test 5: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 2: 100 rpm

Times: 1, 3, 6, 12, and 20 h

Buffer: Add 1 mL of triethylamine in 1000 mL of water. Adjust with phosphoric acid to a pH of 2.5 ± 0.05. Pass through a suitable lter of 0.45-µm pore size.

Mobile phase: Methanol and Buffer (40:60)

Standard stock solution: 0.55 mg/mL of USP Alfuzosin Hydrochloride RS. Prepare by transferring a portion of USP Alfuzosin Hydrochloride RS to a suitable ask. Add methanol to 20% of the ask volume, and sonicate at room temperature to dissolve. Dilute with Medium to volume Standard solution: 0.011 mg/mL of USP Alfuzosin Hydrochloride RS in Medium from the Standard stock solution. Pass through a suitable lter of 0.45-µm pore size.

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

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 245 nm

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

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Column eciency: NLT 2000 theoretical plates

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄· HCl) in the sample withdrawn from the vessel at each time point (i):

Result_i = (r_U /r_S ) × C_S

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Alfuzosin Hydrochloride RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄ · HCl) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = [(C₂ × V) + (C₁ × V_S )] × (1/L) × 100

Result₃ = {(C₃ × V) + [(C₂ + C₁ ) × V_S ]} × (1/L) × 100

Result₄ = {(C₄ × V) + [(C₃ + C₂ + C₁ ) × V_S ]} × (1/L) × 100

Result₅ = ({C₅ × [V − (4 × V_S )]} + [(C₄ + C₃ + C₂ + C₁ ) × V_S]) × (1/L) × 100

C_i = concentration of alfuzosin hydrochloride in the portion of sample withdrawn at the specied time point (mg/mL) i

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: See Table 5.

The percentages of the labeled amount of alfuzosin hydrochloride dissolved at the times specied conform to Dissolution 〈711〉, Acceptance Table 2.

Test 6: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 6.

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 2: 100 rpm. Adjust the paddle height to 4.5 cm above the bottom of the vessel and use a 10# mesh basket as sinker. Times: 1, 6, 12, and 20 h

Buffer: 2.3 g/L of anhydrous dibasic sodium phosphate and 1.75 g/L of monobasic potassium phosphate

Mobile phase: Acetonitrile and Buffer (50:50)

Standard stock solution: 0.45 mg/mL of USP Alfuzosin Hydrochloride RS. Prepare by transferring a portion of USP Alfuzosin Hydrochloride RS to a suitable ask. Add 20% of the ask volume of water. Sonicate to dissolve, and dilute with Medium to volume. Standard solution: 0.011 mg/mL of USP Alfuzosin Hydrochloride RS in Medium from the Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable lter. Replace with the same volume of Medium. Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Column eciency: NLT 3500 theoretical plates

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄ · HCl) in the sample withdrawn from the vessel at each time point (i):

Result_i = (r_U /r_S ) × C_S

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Alfuzosin Hydrochloride RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄ · HCl) dissolved at each time point (i): 

Result₁ = C₁ × V × (1/L) × 100

Result₂ = [(C₂ × V) + (C₁ × V_S )] × (1/L) × 100

Result₃ = {(C₃ × V) + [(C₂ + C₁ ) × V_S ]} × (1/L) × 100

Result₄ = {(C₄ × V) + [(C₃ + C₂ + C₁ ) × V_S ]} × (1/L) × 100

C_i = concentration of alfuzosin hydrochloride in the portion of sample withdrawn at the specied time point (mg/mL)

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: See Table 6.

The percentages of the labeled amount of alfuzosin hydrochloride dissolved at the times specied conform to Dissolution 〈711〉, Acceptance Table 2.

Test 7: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 7.

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 2: 100 rpm with sinker; see Dissolution 〈711〉, Figure 2a.

Times: 1, 6, 12, and 20 h

Solution A: 500 g/L of sodium hydroxide

Solution B: 100 g/L of sodium hydroxide

Buffer: Add 5 mL of perchloric acid in 1000 mL of water. Adjust with Solution A to a pH of 2.5, then adjust with Solution B to a pH of 3.50 ± 0.05. Pass through a suitable lter of 0.45-µm pore size.

Mobile phase: Acetonitrile and Buffer (24:76)

Standard solution: 0.01 mg/mL of USP Alfuzosin Hydrochloride RS in Medium

Sample solution: Centrifuge or pass a portion of the solution under test through a suitable lter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 245 nm

Column: 4.6-mm × 5-cm; 3-µm packing L7

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: NLT 1.5 times the retention time of alfuzosin

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.8

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄· HCl) in the sample withdrawn from the vessel at each time

point (i):

Result_i = (r_U /r_S ) × C_S

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Alfuzosin Hydrochloride RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄ · HCl) dissolved at each time point (i): 19 27 5 4

Result₁ = C₁ × V × (1/L) × 100

Result₂ = [(C₂ × V) + (C₁ × V_S )] × (1/L) × 100

Result₃ = {(C₃ × V) + [(C₂ + C₁ ) × V_S ]} × (1/L) × 100

Result₄ = {(C₄ × V) + [(C₃ + C₂ + C₁ ) × V_S ]} × (1/L) × 100

C_i = concentration of alfuzosin hydrochloride in the portion of sample withdrawn at the specied time point (mg/mL)

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: See Table 7.

The percentages of the labeled amount of alfuzosin hydrochloride dissolved at the times specied conform to Dissolution 〈711〉, Acceptance Table 2.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

5.1 Organic Impurities

Solution A, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay. System suitability stock solution: 0.4 mg/mL of USP Alfuzosin System Suitability Mixture A RS in methanol System suitability solution: 0.03 mg/mL of USP Alfuzosin System Suitability Mixture A RS in Diluent from the System suitability stock solution Standard stock solution: 0.15 mg/mL of USP Alfuzosin Hydrochloride RS in methanol

Standard solution: 0.03 mg/mL of USP Alfuzosin Hydrochloride RS in Diluent from the Standard stock solution System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.0 between alfuzosin and the furamide analog; NLT 1.0 between deacylated alfuzosin and the N-formyl analog, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

5.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of alfuzosin from the Standard (ERR 1-Nov-2021) solution

C_S = concentration of USP Alfuzosin Hydrochloride RS in the Standard solution (mg/mL)

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

Acceptance criteria: See Table 8. 

a N2-(3-Aminopropyl)-6,7-dimethoxy-N2-methylquinazoline-2,4-diamine.

b N-[3-[(4-Amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl]formamide.

c N-{3-[(4-Amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl}furan-2-carboxamide.

d Furamide analog, a component of USP Alfuzosin System Suitability Mixture A RS, is not a specied impurity.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Protect from light and moisture. Store at controlled room temperature.

Labeling: 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 Alfuzosin Hydrochloride RS

USP Alfuzosin System Suitability Mixture A RS

Furamide analog: N-{3-[(4-Amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl}furan-2-carboxamide.

C₁₉H₂₃N₅O₄      385.42

Deacylated alfuzosin: N²-(3-Aminopropyl)-6,7-dimethoxy-N²-methylquinazoline-2,4-diamine.

C₁₄H₂₁N₅O₂   291.35

N-Formyl analog: N-[3-[(4-Amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl]formamide.

C₁₅H₂₁N₅O₃   319.36