Propranolol Hydrochloride Extended-Release Capsules
DEFINITION
Propranolol Hydrochloride Extended-Release Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of propranolol hydrochloride (C16H21NO2·HCl).
IDENTIFICATION
• Infrared Absorption 
197M
197M
Sample:
Transfer the contents of a number of Capsules, equivalent to 160 mg of propranolol hydrochloride, to a glass mortar. Add 5 mL of water, and triturate the mixture with a glass pestle. Transfer the suspension to a centrifuge tube with the aid of 10 mL of water. Add 1 mL of 1 N sodium hydroxide. Add 15 mL of ether, and shake by mechanical means for 5 min. Centrifuge the mixture, and transfer as much of the ether layer as possible to a second centrifuge tube. Add 0.1 mL of hydrochloric acid to the ether extract, and shake. Centrifuge, and discard the ether layer. Add 15 mL of ether to the precipitate, and shake by mechanical means for 5 min. Centrifuge, and discard the ether layer. Dry the precipitate in vacuum at 45
for 30 min. Transfer a small amount of the dried precipitate to a mortar, and grind to a fine powder.
for 30 min. Transfer a small amount of the dried precipitate to a mortar, and grind to a fine powder.
ASSAY
• Procedure
Buffer:
6.8 mg/mL of monobasic potassium phosphate. Pass the solution through a filter of 0.5-µm or finer pore size before use.
Mobile phase:
Acetonitrile and Buffer (7:13)
Diluent:
Acetonitrile and water (7:13)
Standard stock solution:
200 µg/mL of USP Propranolol Hydrochloride RS in methanol
Standard solution:
20 µg/mL in Diluent from Standard stock solution
Sample stock solution
Transfer the contents of Capsules (NLT 10) to a suitable volumetric flask. Add methanol (60% of the volume of the flask), and swirl by mechanical means for 2 h. Allow to stand for 16 h, then sonicate for 30 min, and swirl for 30 min. Dilute with methanol to volume, and centrifuge a portion of the solution. Use the clear supernatant for further use.
Sample solution:
Nominally equivalent to 20 µg/mL of propranolol hydrochloride in Diluent from Sample stock solution
Chromatographic system
Mode:
LC
Detector:
UV 220 nm
Column:
4-mm × 15-cm; 5-µm packing L1
Flow rate:
2 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
[Note—The retention time for propranolol is about 5–9 min. ]
Suitability requirements
Column efficiency:
NLT 1000 theoretical plates
Tailing factor:
NMT 3
Relative standard deviation:
NMT 2%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C16H21NO2·HCl in each Capsule taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Propranolol Hydrochloride RS in the Standard solution (µg/mL) |
| CU | = | = nominal concentration of propranolol hydrochloride in the Sample solution (µg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
711
Test 1:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 1.
pH 1.2 buffer solution:
Dissolve 2.0 g of sodium chloride in water, add 7.0 mL of hydrochloric acid, and dilute with water to 1 L.
pH 6.8 buffer solution:
21.72 mg/mL of anhydrous dibasic sodium phosphate and 4.94 mg/mL of citric acid monohydrate in water
Media:
Proceed as directed under Method B for Delayed-Release Dosage Forms, using 900 mL of pH 1.2 buffer solution during the Acid stage, and conduct the test for 1.5 h. For the Buffer stage, use 900 mL of pH 6.8 buffer solution, conduct the test for 2.5 h (this is the 4-h time point: 1.5 h in Acid stage plus 2.5 h in Buffer stage), conduct the test for the additional time points, always considering T1 = 1.5 h, and use the acceptance criteria given under Tolerances.
Apparatus 1:
100 rpm
Times:
1.5, 4, 8, 14, and 24 h
Standard solution:
USP Propranolol Hydrochloride RS at a known concentration in water
Sample solution:
Pass a portion of the solution under test through a suitable filter. Dilute with Medium, if necessary.
Spectrometric conditions
Mode:
UV
Analytical wavelength:
Maximum absorbance at 320 nm, with respect to a baseline drawn from 355 nm through 340 nm
Analysis
Samples:
Standard solution and Sample solution
Tolerances:
The percentages of the labeled amount of C16H21NO2·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved |
|---|---|
| 1.5 | NMT 30% |
| 4 | 35%–60% |
| 8 | 55%–80% |
| 14 | 70%–95% |
| 24 | 81%–110% |
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
pH 1.2 buffer solution:
Dissolve 2.0 g of sodium chloride in water, add 7.0 mL of hydrochloric acid, and dilute with water to 1 L.
pH 7.5 buffer solution:
Dissolve 6.8 g of monobasic potassium phosphate and 1.6 g of sodium hydroxide in 900 mL of water, adjust with 1 N sodium hydroxide to a pH of 7.5, and dilute with water to 1 L.
Media:
Proceed as directed under Method B for Delayed-Release Dosage Forms, using 900 mL of pH 1.2 buffer solution during the Acid stage, and conduct the test for 1 h. For the Buffer stage, use 900 mL of pH 7.5 buffer solution, conduct the test for 2 h (this is the 3-h time point: 1 h in Acid stage plus 2 h in Buffer stage), conduct the test for the additional time points, always considering T1 = 1 h, and use the acceptance criteria given under Tolerances.
Apparatus 1:
50 rpm
Times:
1, 3, 6, and 12 h
Standard solution:
USP Propranolol Hydrochloride RS at a known concentration in water
Sample solution:
Pass a portion of the solution under test through a suitable filter. Dilute with Medium, if necessary.
Spectrometric conditions and Analysis:
Proceed as directed under Test 1.
Tolerances:
The percentages of the labeled amount of C16H21NO2·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | NMT 20% |
| 3 | 20%–45% |
| 6 | 45%–80% |
| 12 | NLT 80% |
Test 3:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Acid stage medium:
pH 1.2 buffer solution (prepared by dissolving 2.0 g of sodium chloride in water, adding 7.0 mL of hydrochloric acid, and diluting with water to 1000 mL); 900 mL
Buffer stage medium:
pH 6.8 phosphate buffer; 900 mL
Apparatus 1:
100 rpm
Standard stock solution:
1 mg/mL of USP Propranolol Hydrochloride RS in water
Working standard solution:
Quantitatively dilute the Standard stock solution with water to obtain a final concentration of about (L/1000) mg per mL, where L is the Capsule label claim in mg.
Analysis:
Conduct the test in Acid stage medium for 1.5 h, sample, and pass through a suitable filter of 0.45-µm or finer pore size. Replace the Acid stage medium with the Buffer stage medium, and conduct the test for 2.5 h (this is the 4-h time point: 1.5 h in Acid stage medium plus 2.5 h in Buffer stage medium), conduct the test for the additional time points, always considering T1 = 1.5 h, and use the acceptance criteria given under Tolerances. Determine the amount of C16H21NO2·HCl dissolved, using UV absorbances at the wavelength of maximum absorbance at about 320 nm, with respect to a baseline drawn from 355 nm through 340 nm, using a 1-cm cell and water as the blank.
Determine the percentage of propanolol hydrochloride dissolved using the spectrophotometric procedure as directed for Test 1.
Tolerances:
The percentages of the labeled amount of C16H21NO2·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved |
|---|---|
| 1.5 | NMT 15% |
| 4 | NMT 30% |
| 8 | 25%–60% |
| 14 | 55%–85% |
| 24 | NLT 75% |
Test 4:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.
Acid stage medium:
pH 1.2 buffer solution (prepared by dissolving 2.0 g of sodium chloride in water, adding 7.0 mL of hydrochloric acid, and diluting with water to 1000 mL); 900 mL, deaerated
Buffer stage medium:
pH 6.8 phosphate buffer; 900 mL, deaerated
Apparatus 1:
100 rpm
Times:
1.5 h in acid stage; 4, 8, 14, and 24 h in buffer stage
Standard solution:
0.18 mg/mL of USP Propranolol Hydrochloride RS in water
Analysis:
Conduct the test in Acid stage medium for 1.5 h, sample, and pass through a suitable filter of 10-µm or finer pore size. Replace the Acid stage medium with the Buffer stage medium, and conduct the test for 2.5 h (this is the 4-h time point: 1.5 h in Acid stage medium plus 2.5 h in Buffer stage medium), conduct the test for the additional time points, always considering T1 = 1.5 h, and use the acceptance criteria given under Tolerances. Determine the amount of C16H21NO2·HCl dissolved, using UV absorbances at the wavelength of maximum absorbance at about 320 nm, with respect to a baseline drawn from 355 nm through 340 nm, using a 1-cm cell and water as the blank.
Tolerances:
The percentages of the labeled amount of C16H21NO2·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved |
|---|---|
| 1.5 | NMT 30% |
| 4 | 27%–52% |
| 8 | 52%–77% |
| 14 | 70%–95% |
| 24 | 81%–110% |
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
Procedure for content uniformity
Standard solution:
40 µg/mL of USP Propranolol Hydrochloride RS in methanol
Sample stock solution:
Transfer the contents of 1 Capsule to a suitable volumetric flask. Add methanol (70% of the volume of the flask), swirl occasionally for 30 min, sonicate for 1 min, and then swirl occasionally for an additional 30 min. Dilute with methanol to volume, and centrifuge a portion of the solution. Use the clear supernatant for preparing the Sample solution.
Sample solution:
Equivalent to 40 µg/mL in methanol from Sample stock solution
Spectrometric conditions
Mode:
UV
Analytical wavelength:
290 nm
Cell:
1 cm
Blank:
Methanol
Calculate the percentage of C16H21NO2·HCl in the Capsule taken:
Result = (AU/AS) × (CS/CU) × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of USP Propranolol Hydrochloride RS in the Standard solution (µg/mL) |
| CU | = | = concentration of the Sample solution (µg/mL) |
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers.
• Labeling:
The labeling states the Dissolution Test with which the product complies.
• USP Reference Standards 11
11
USP Propranolol Hydrochloride RS
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison 1-301-816-8349 |
(SM22010) Monographs - Small Molecules 2 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4462
Pharmacopeial Forum: Volume No. 35(5) Page 1096