Dissolution 
711
—
Medium:
0.1 N hydrochloric acid; 900 mL.
Apparatus 2:
50 rpm.
Time:
30 minutes.
Procedure—
Determine the amount of C
13H
14N
2 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 240 nm on filtered portions of the solution under test, suitably diluted with
Dissolution Medium, in comparison with a Standard solution having a known concentration of
USP Tacrine Hydrochloride RS in the same
Medium.
Tolerances—
Not less than 85% (Q) of the labeled amount of C13H14N2 is dissolved in 30 minutes.
Uniformity of dosage units 905:
meet the requirements.
PROCEDURE FOR CONTENT UNIFORMITY—
Standard solution—
Dissolve an accurately weighed quantity of
USP Tacrine Hydrochloride RS in 0.1 N hydrochloric acid, and dilute quantitatively, and stepwise if necessary, with 0.1 N hydrochloric acid to obtain a solution having a known concentration of about 4.1 µg per mL.
Test solution—
Place 1 intact Capsule in a 100-mL volumetric flask, add about 70 mL of 0.1 N hydrochloric acid, and sonicate until the gelatin capsule shell has dissolved completely (about 15 minutes). [NOTE—Periodically swirl the flask during the sonication to loosen the Capsule from the bottom of the flask and to dissolve a floating Capsule.] Shake mechanically for about 30 additional minutes, dilute with 0.1 N hydrochloric acid to volume, and mix. Pass a portion of the solution through a suitable filter, and dilute quantitatively with 0.1 N hydrochloric acid to obtain a solution having a concentration of about 4.1 µg of tacrine hydrochloride per mL. [NOTE—Do not use nylon filters.] Immediately prior to removing an aliquot for analysis, mix the solution vigorously.
Blank—
Place an empty Capsule of each Capsule strength into a separate 100-mL volumetric flask and prepare as directed for Test solution.
Procedure—
Concomitantly determine the absorbances at 240 nm of the
Blank, the
Standard solution, and the
Test solution with a suitable spectrophotometer. Calculate the quantity, in mg, of tacrine (C
13H
14N
2) in the Capsule taken by the formula:
1000L(CS / CU)(198.27/234.73)(AU / AS),
in which
L is the labeled quantity, in mg, of tacrine hydrochloride in the Capsule;
CS is the concentration, in µg per mL, of
USP Tacrine Hydrochloride RS in the
Standard solution; CU is the concentration, in µg per mL, of tacrine hydrochloride in the
Test solution, based on the labeled quantity per Capsule and the extent of dilution; 198.27 and 234.73 are the molecular weights of tacrine and tacrine hydrochloride, respectively; and
AU and
AS are the absorbances obtained from the
Test solution and the
Standard solution, respectively.
Assay—
0.1 M Triethylamine phosphate solution—
Transfer 28 mL of triethylamine to a 2000-mL volumetric flask containing about 1800 mL of water, and mix. Adjust with phosphoric acid to a pH of 3.25, dilute with water to volume, and mix.
Mobile phase—
Prepare a filtered and degassed mixture of
0.1 M Triethylamine phosphate solution and methanol (85:15). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard preparation—
Dissolve an accurately weighed quantity of
USP Tacrine Hydrochloride RS in
Mobile phase, and dilute quantitatively, and stepwise if necessary, with
Mobile phase to obtain a solution having a known concentration of about 100 µg of tacrine per mL.
Assay preparation—
Transfer 10 Capsules to a 1000-mL volumetric flask containing 500 mL of Mobile phase. Sonicate for about 45 minutes until the gelatin capsule shells have dissolved. Periodically swirl the flask during sonication to loosen any Capsules sticking to the bottom of the flask and to dissolve floating Capsules. Add an additional 300 mL of Mobile phase, shake for 30 minutes on a mechanical shaker, dilute with Mobile phase to volume, and mix. Pass an aliquot of this solution through an appropriate filter presaturated with the solution, and dilute, if necessary, with Mobile phase to obtain a solution containing about 100 µg of tacrine per mL.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a variable wavelength detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 2.5 mL per minute. Initially, the detector is maintained at a wavelength of 240 nm. At 7.0 minutes, the wavelength is changed to 260 nm. Chromatograph the
Standard preparation, and record the peak responses as directed for
Procedure: the column efficiency is not less than 3500 theoretical plates; the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 1.0%.
Procedure—
Separately inject equal volumes (about 30 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of tacrine (C
13H
14N
2) in the portion of Capsules taken by the formula:
1000C(198.27/234.73)(rU / rS),
in which
C is the concentration, in mg per mL, of
USP Tacrine Hydrochloride RS in the
Standard preparation; 198.27 and 234.73 are the molecular weights of tacrine and tacrine hydrochloride, respectively; and
rU and
rS are the peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.
for 90 minutes. Prepare a mixture of about 0.5% to 1.0% of the isolated solid in potassium bromide.