Medium: pH 6.5 phosphate buffer with 1% of sodium lauryl sulfate (Transfer 206 mL of 1 M monobasic sodium phosphate monohydrate, 196 mL of 0.5 M dibasic sodium phosphate anhydrous, and 50.0 g of sodium lauryl sulfate to a 5000-mL volumetric flask. Add approximately 4000 mL of water, and mix well. If necessary, adjust with 1 N sodium hydroxide to a pH of 6.5. Dilute with water to volume, and mix well.); 500 mL.

Apparatus 2: 50 rpm.

Times: 2, 6, and 10 hours.

Buffer solution— Prepare as directed in the Assay.

Mobile phase— Prepare a filtered and degassed mixture of acetonitrile, Buffer solution, and methanol (2.5:2:1). Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard stock solution— Dissolve an accurately weighed quantity of USP Felodipine RS in alcohol to obtain a solution having a known concentration of 0.25 mg per mL.

Standard solution— Dilute an accurately measured volume of the Standard stock solution quantitatively, and stepwise if necessary, with Medium to obtain a solution having a known concentration of USP Felodipine RS equivalent to the concentration that would result from about 60% dissolution of a single Tablet in 500 mL of Medium.

Test solution— Place each Tablet in a specially made quadrangular basket of stainless steel wire gauze, soldered in one of its upper, narrow sides to the end of a steel rod (see Figure 1). Place the tablet cover in the horizontal diagonal of the basket. Put the rod assembly up through the cover of the dissolution vessel, and fix it by means of two teflon nuts, 3.2 cm from the center of the vessel, or by any other appropriate means. Adjust the lower edge of the bottom of the basket to approximately 1 cm above the top of the paddle blade (see Figure 2). Orient the large side of the basket tangentially to the flow stream with the Tablet standing on its edge. Pass a 10-mL portion of the solution under test, obtained at each time interval, through a suitable filter.

Chromatographic system— Proceed as directed in the Assay.

Procedure— Separately inject equal volumes (100 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of felodipine (C18H19Cl2NO4) dissolved in the Medium by the formula: in which C is the concentration, in mg per mL, of USP Felodipine RS in the Standard solution; D is the dilution factor used in preparing the Test solution; and rU and rS are the felodipine peak areas obtained from the Test solution and the Standard solution, respectively.

Tolerances— The percentages of the labeled amount of C18H19ClNO4 dissolved at the times specified conform to Acceptance Table 1 under Drug Release 724.

Medium: pH 6.5 phosphate buffer with 1% sodium lauryl sulfate; 500 mL. (Medium is prepared as follows. Transfer 206 mL of 1 M monobasic sodium phosphate monohydrate, 196 mL of 0.5 M dibasic sodium phosphate anhydrous, and 50.0 g of sodium lauryl sulfate to a 5000-mL volumetric flask. Add approximately 4000 mL of water, and mix well. If necessary, adjust with 1 N sodium hydroxide to a pH of 6.5. Dilute with water to volume, and mix well.)

Apparatus 2: 50 rpm.

Times: 2, 6, and 10 hours.

Buffer solution— Prepare as directed in the Assay.

Mobile phase— Prepare a filtered and degassed mixture of acetonitrile, Buffer solution, and methanol (2.5:2:1). Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard stock solution— Dissolve an accurately weighed quantity of USP Felodipine RS in alcohol to obtain a solution having a known concentration of 0.25 mg per mL.

Standard solution— Dilute an accurately measured volume of the Standard stock solution quantitatively, and stepwise if necessary, with Medium to obtain a solution having a known concentration of USP Felodipine RS equivalent to the concentration that would result from about 60% dissolution of a single Tablet in 500 mL of Medium.

Test solution— Place each Tablet in a specially made quadrangular basket of stainless steel wire gauze, soldered in one of its upper, narrow sides to the end of a steel rod (see Figure 1). Place the tablet cover in the horizontal diagonal of the basket. Put the rod assembly up through the cover of the dissolution vessel, and fix it by means of two teflon nuts, 3.2 cm from the center of the vessel, or by any other appropriate means. Adjust the lower edge of the bottom of the basket to approximately 1 cm above the top of the paddle blade (see Figure 2). Orient the large side of the basket tangentially to the flow stream with the Tablet standing on its edge. Pass a 10-mL portion of the solution under test, obtained at each time interval, through a suitable filter.

Chromatographic system— Proceed as directed in the Assay.

Procedure— Separately inject equal volumes (100 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of felodipine (C18H19Cl2NO4) dissolved in the Medium by the formula: in which C is the concentration, in mg per mL, of USP Felodipine RS in the Standard solution; D is the dilution factor used in preparing the Test solution; and rU and rS are the felodipine peak areas obtained from the Test solution and the Standard solution, respectively.

Tolerances— The percentages of the labeled amount of C18H19ClNO4 dissolved at the times specified conform to Acceptance Table 2.

(Official April 1, 2006)

PROCEDURE FOR CONTENT UNIFORMITY—

Buffer solution and Mobile phase— Prepare as directed in the Assay.

Standard stock solution 1— Dissolve an accurately weighed quantity of USP Felodipine Related Compound A RS in methanol to obtain a solution having a known concentration of about 0.2 mg per mL. Transfer 10.0 mL of this solution to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.

Standard stock solution 2— Dissolve an accurately weighed quantity of USP Felodipine RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of about 2 mg per mL.

System suitability solution— Transfer 15.0 mL of Standard stock solution 1 and 5.0 mL of Standard stock solution 2 to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.

Standard solution— Transfer 10.0 mL of Standard stock solution 1 to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.

Test solution— Proceed as directed for the Assay preparation in the Assay, except that after centrifuging a portion of the solution at high speed for 15 minutes, pass a portion of the supernatant through a filter having a 0.5-µm or finer porosity, discarding the first 4 mL of the filtrate.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 15-cm column that contains packing L1. The flow rate is about 1 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are 0.75 for felodipine related compound A and 1.0 for felodipine; the resolution, R, between felodipine and felodipine related compound A is not less than 1.5; and the column efficiency is not less than 1500 theoretical plates.

Procedure— Separately inject equal volumes (about 40 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses for felodipine related compound A. Calculate the percentage of felodipine related compound A in the portion of Tablets taken by the formula: in which C is the concentration, in mg per mL, of USP Felodipine Related Compound A RS in the Standard solution; and rU and rS are the peak responses of felodipine related compound A obtained from the Test solution and the Standard solution, respectively: not more than 2.0% is found.

(Official January 1, 2007)

Buffer solution— Dissolve 6.9 g of monobasic sodium phosphate in about 800 mL of water in a 1000-mL volumetric flask. Adjust with 1 M phosphoric acid to a pH of 3.0 ± 0.05, dilute with water to volume, and mix.

Mobile phase— Prepare a filtered and degassed mixture of Buffer solution, acetonitrile, and methanol (2:2:1). Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard stock preparation— Dissolve an accurately weighed quantity of USP Felodipine RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of about 2 mg per mL.

Standard preparation— Dilute an accurately measured volume of the Standard stock preparation quantitatively and stepwise with Mobile phase to obtain a solution having a known concentration of about 0.02 mg per mL.

Assay preparation— Weigh and finely powder not fewer than 10 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 10 mg of felodipine, to a 100-mL volumetric flask, add 40 mL of acetonitrile and 20 mL of methanol, and sonicate for 5 minutes. Add about 30 mL of Buffer solution, and shake by mechanical means for 30 minutes. Allow the solution to cool to room temperature, dilute with Buffer solution to volume, and mix. Centrifuge a portion of the solution at high speed for 15 minutes. Transfer 10 mL of the supernatant to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. Pass a portion of this solution through a filter having a 0.5-µm or finer porosity, discarding the first 4 mL of the filtrate.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 362-nm detector and a 4.6-mm × 15-cm column that contains packing L1. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 1500 theoretical plates; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 40 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 felodipine (C18H19Cl2NO4) in the portion of Tablets taken by the formula: in which C is the concentration, in mg per mL, of USP Felodipine RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.