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.
Drug release 
724
—
Test 1—
If the product complies with this test, the labeling indicates that it meets USP
Drug Release 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 (Enteric-Coated) Articles, 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 Tolerances. 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 C
16H
21NO
2·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 C
16H
21NO
2·HCl dissolved at the times specified conform to
Acceptance Table 1.
| 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
Drug Release 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 (Enteric-Coated) Articles—General Drug Release Standard, using 900 mL of pH 1.2 Buffer solution during the Acid stage, run for 1 hour, and use the acceptance criteria given under Tolerances. 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 C
16H
21NO
2·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 C
16H
21NO
2·HCl dissolved at the times specified conform to
Acceptance Table 1.
| Time (hours) |
Amount dissolved |
| 1 |
not more than 20% |
| 3 |
between 20% and 45% |
| 6 |
between 45% and 80% |
| 12 |
not less than 80% |
Dissolution 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 C
16H
21NO
2·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 C
16H
21NO
2·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 C
16H
21NO
2·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 C
16H
21NO
2·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% |
(Official April 1, 2006)
Uniformity of dosage units 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 C
16H
21NO
2·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).
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%.
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 (C
16H
21NO
2·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.
