Propranolol Hydrochloride Extended-Release Capsules
» Propranolol Hydrochloride Extended-Release Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of propranolol hydrochloride (C16H21NO2·HCl).
Packaging and storage—
Preserve in well-closed containers.
Labeling—
The labeling states the Dissolution Test with which the product complies.
Identification—
Transfer the contents of a number of Capsules, equivalent to about 160 mg of propranolol hydrochloride, to a glass mortar. Add about 5 mL of water, and triturate the mixture with a glass pestle. Transfer the suspension to a centrifuge tube with the aid of about 10 mL of water. Add 1 mL of 1 N sodium hydroxide, and mix. Add 15 mL of ether, and shake by mechanical means for about 5 minutes. 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 about 5 minutes. Centrifuge, and discard the ether layer. Dry the precipitate in vacuum at about 45
for 30 minutes. Transfer a small amount of the dried precipitate to a mortar, and grind to a fine powder: the IR absorption spectrum of a mineral oil dispersion of the powder so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Propranolol Hydrochloride RS.
for 30 minutes. Transfer a small amount of the dried precipitate to a mortar, and grind to a fine powder: the IR absorption spectrum of a mineral oil dispersion of the powder so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Propranolol Hydrochloride RS.
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, dilute with water to 1 L, and mix.
pH 6.8 Buffer solution—
Dissolve 21.72 g of anhydrous dibasic sodium phosphate and 4.94 g of citric acid monohydrate in water, dilute with water to 1 L, and mix.
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, run for 1.5 hours, and use the acceptance criteria given under Acceptance Table 3. For the Buffer stage, use 900 mL of pH 6.8 Buffer solution, run for the time specified, and use the acceptance criteria given under Tolerances.
Apparatus 1:
100 rpm.
Times:
1.5, 4, 8, 14, and 24 hours.
Procedure—
Using filtered portions of the solution under test, diluted if necessary, 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, by comparison with a Standard solution in water having a known concentration of USP Propranolol Hydrochloride RS.
Tolerances—
The percentages of the labeled amount of C16H21NO2·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (hours) |  Amount dissolved |
| 1.5 | not more than 30% |
| 4 | between 35% and 60% |
| 8 | between 55% and 80% |
| 14 | between 70% and 95% |
| 24 | between 81% and 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, dilute with water to 1 L, and mix.
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, dilute with water to 1 L, and mix.
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, run for 1 hour, and use the acceptance criteria given under Acceptance Table 3. For the Buffer stage, use 900 mL of pH 7.5 Buffer solution, run for the time specified, and use the acceptance criteria given under Tolerances.
Apparatus 1:
50 rpm.
Times:
1, 3, 6, and 12 hours.
Procedure—
Using filtered portions of the solution under test, diluted if necessary, 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, by comparison with a Standard solution in water having a known concentration of USP Propranolol Hydrochloride RS.
Tolerances—
The percentages of the labeled amount of C16H21NO2·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (hours) | Amount dissolved |
| 1 | not more than 20% |
| 3 | between 20% and 45% |
| 6 | between 45% and 80% |
| 12 | not less than 80% |
Uniformity of dosage units 905:
meet the requirements.
905:
meet the requirements.
Procedure for content uniformity—
Transfer the contents of 1 Capsule to a 100-mL volumetric flask, add about 70 mL of methanol, swirl occasionally for 30 minutes, and sonicate for about 1 minute, and then swirl occasionally for an additional 30 minutes. Dilute with methanol to volume, mix, and centrifuge a portion of the solution. Quantitatively dilute an accurately measured volume of the clear solution with methanol to obtain a solution containing about 40 µg of propranolol hydrochloride per mL. Concomitantly determine the absorbances of this solution and a Standard solution of USP Propranolol Hydrochloride RS in methanol having a known concentration of about 40 µg per mL, in 1-cm cells at the wavelength of maximum absorbance at about 290 nm, with a suitable spectrophotometer, using methanol as the blank. Calculate the quantity, in mg, of C16H21NO2·HCl in the Capsule taken by the formula:
(LC / D)(AU / AS)
in which L is the labeled quantity, in mg, of propranolol hydrochloride in the Capsule; C is the concentration, in µg per mL, of USP Propranolol Hydrochloride RS in the Standard solution; D is the concentration, in µg per mL, of the solution from the Capsule, based on the labeled quantity per Capsule and the extent of dilution; and AU and AS are the absorbances of the solution from the Capsule and the Standard solution, respectively.
Assay—
Phosphate buffer—
Dissolve 13.6 g of monobasic potassium phosphate in 2 L of water, and mix. Pass the solution through a filter having a 0.5-µm or finer porosity before use.
Mobile phase—
Prepare a suitable degassed mixture of Phosphate buffer and acetonitrile (650:350). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Diluting solvent—
Mix 650 mL of water with 350 mL of acetonitrile.
Standard preparation—
Dissolve an accurately weighed quantity of USP Propranolol Hydrochloride RS in methanol, and dilute quantitatively and stepwise with methanol to obtain a solution having a known concentration of about 200 µg per mL. Transfer 5.0 mL of this solution to a 50.0-mL volumetric flask, add Diluting solvent to volume, and mix.
Assay preparation—
Transfer the contents of 10 Capsules, accurately counted, to a 500-mL volumetric flask. Add 300 mL of methanol, and swirl by mechanical means for 2 hours. Allow to stand for about 16 hours, then sonicate for one-half hour, and swirl for one-half hour. Quantitatively dilute with methanol to volume, mix, and centrifuge a portion of the solution. Dilute an accurately measured volume of the clear solution with Diluting solvent to obtain a solution having a concentration of about 20 µg of propranolol hydrochloride per mL.
Chromatographic system
(see Chromatography 621)—The liquid chromatograph is equipped with a 220-nm detector and a 4-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the retention time of propranolol is about 5 to 9 minutes; the column efficiency determined from the analyte peak is not less than 1000 theoretical plates; the tailing factor for the analyte peak is not more than 3; and the relative standard deviation for replicate injections is not more than 2%.
621)—The liquid chromatograph is equipped with a 220-nm detector and a 4-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the retention time of propranolol is about 5 to 9 minutes; the column efficiency determined from the analyte peak is not less than 1000 theoretical plates; the tailing factor for the analyte peak is not more than 3; and the relative standard deviation for replicate injections is not more than 2%.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of propranolol hydrochloride (C16H21NO2·HCl) in each Capsule taken by the formula:
(LC / D)(rU / rS)
in which L is the labeled quantity, in mg, of propranolol hydrochloride in each Capsule; C is the concentration, in µg per mL, of USP Propranolol Hydrochloride RS in the Standard preparation; D is the concentration, in µg of propranolol hydrochloride per mL, of the Assay preparation, based on the labeled quantity per Capsule, the number of Capsules taken, and the extent of dilution; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
Chromatographic Column—
| Topic/Question | Contact | Expert Committee |
| Monograph | Sujatha Ramakrishna, Ph.D.
Scientist 1-301-816-8349 |
(MDCV05) Monograph Development-Cardiovascular |
| Reference Standards | Lili Wang, Technical Services Scientist 1-301-816-8129 RSTech@usp.org |
|
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientist 1-301-816-8106 |
(BPC05) Biopharmaceutics05 |
USP32–NF27 Page 3426
Pharmacopeial Forum: Volume No. 31(1) Page 180
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.