Didanosine Tablets for Oral Suspension
» Didanosine Tablets for Oral Suspension contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of didanosine (C10H12N4O3).
Packaging and storage— Preserve in tight containers, and store between 15 and 30.
Labeling— The label states that the Tablets are not to be swallowed whole, and that they may be chewed or dispersed in water before administration.
Identification— The retention time of the major peak in the chromatogram of the Diluted assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 711
Medium: water; 900 mL.
Apparatus 2: 75 rpm.
Time: 30 minutes.
Determine the amount of C10H12N4O3 dissolved by employing the following method.
0.01 M Ammonium acetate buffer solution and Mobile phase— Proceed as directed in the Assay.
Standard stock solution— Transfer about 160 mg of USP Didanosine RS, accurately weighed, to a 200-mL volumetric flask. Add about 100 mL of water, shake, and sonicate for 30 seconds to dissolve. Dilute with water to volume. [note—This solution is stable for 48 hours at 5.]
Working standard solution— Dilute the Standard stock solution in water to obtain a concentration of approximately LC/900, where LC is the label claim of the Tablet for didanosine.
Test solution— Pass a portion of the solution under test through a suitable filter having a porosity of 0.45 µm.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a variable wavelength detector set at 275 nm, and a 4-mm × 12.5-cm column that contains 5-µm packing L7. The flow rate is about 2 mL per minute. Chromatograph the Working standard solution, and record the peak responses as directed for Procedure: didanosine elutes at about 4.8 minutes; the column efficiency is not less than 1000 theoretical plates; the tailing factor is not more than 2; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes, equivalent to approximately 2 µg of didanosine, of the Working standard solution and the Test solution into the chromatograph, record the chromatograms for at least 7 minutes, and measure the responses for the didanosine peaks. Calculate the percentage of C10H12N4O3 released by the formula:
Click to View Image
in which rU and rS are the peak responses obtained from the Test solution and the Working standard solution, respectively; CS is the concentration, in mg per mL, of the Working standard solution; 900 is the volume, in mL, of the Medium; 100 is the conversion factor to percentage; and LC is the Tablet label claim, in mg.
Tolerances— Not less than 80% (Q) of the labeled amount of C10H12N4O3 is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Loss on drying 731 Dry 4 Tablets for Oral Suspension at 130 for 16 hours: they lose not more than 6% of their weight.
Acid-neutralizing capacity 301: not less than 17 mEq per Tablet.
Related compounds—
0.01 M Ammonium acetate buffer solution— Prepare as directed in the Assay.
Mobile phase— Prepare a filtered and degassed mixture of 0.01 M Ammonium acetate buffer solution and methanol (99:1).
Standard stock solution— Transfer 25 mg of USP Didanosine Related Compound A RS to a 200-mL volumetric flask. Dissolve in and dilute with water to volume, and mix. [note—Use this solution within 48 hours of preparation.]
Standard solution— Transfer 3 mL of the Standard stock solution to a 250-mL volumetric flask. Dilute with water to volume, and mix. [note—Use this solution within 48 hours of preparation of the Standard stock solution.]
Test solution— Proceed as directed for the Assay preparation.
Diluted test solution— Dilute the Test solution quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a concentration of about 0.1 mg per mL.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a variable wavelength detector set at 275 nm, a 4-mm × 12.5-cm column that contains 5-µm packing L7, and a matching guard column. The flow rate is about 2.0 mL per minute. Chromatograph the Standard solution as directed for Procedure: the column efficiency is not less than 1000 theoretical plates; and the relative standard deviation for replicate injections is not more than 5.0%. [note—For information purposes only, didanosine related compound A, with a retention time between 1.5 and 2.5 minutes, is hypoxanthine.]
Procedure— Separately inject equal volumes (about 100 µL) of the Standard solution and the Diluted test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks, carrying out the chromatography for approximately 30 minutes. Calculate the percentage of didanosine related compound A in the portion of Tablets for Oral Suspension taken by the formula:
100(CVD/NL)(rU / rS)
in which C is the concentration, in mg per mL, of USP Didanosine Related Compound A RS in the Standard solution; V is the volume, in mL, of the Test solution; D is the dilution factor of the Diluted test solution; N is the number of Tablets for Oral Suspension used to prepare the Test solution; L is the label claim of didanosine, in mg per Tablet; and rU and rS are the peak responses obtained from the Diluted test solution and the Standard solution, respectively. Not more than 0.7% of didanosine related compound A is found. Calculate the percentage of any other impurity by the formula:
100(ri / rs)
in which ri is the peak response of any other individual impurity in the chromatogram of the Diluted test solution; and rs is the sum of the responses of all the peaks in the chromatogram of the Diluted test solution, including those of didanosine and hypoxanthine: not more than 0.2% of any other individual impurity is found; and not more than 1.2% of total impurities, excluding hypoxanthine, is found.
Assay—
0.01 M Ammonium acetate buffer solution— Dissolve 1.54 g of ammonium acetate in a 2000-mL volumetric flask, dilute with water to volume, and mix.
Mobile phase— Prepare a filtered and degassed mixture of 0.01 M Ammonium acetate buffer solution and methanol (95:5). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Didanosine RS in water to obtain a solution having a known concentration of 0.1 mg per mL. [note—Use this solution within 24 hours of preparation.]
Assay preparation— Transfer not fewer than 5 crushed Tablets for Oral Suspension to a 500-mL volumetric flask. Dissolve in 250 mL of water, dilute with water to volume, and shake for about 10 minutes.
Diluted assay preparation— Dilute the Assay preparation quantitatively, and stepwise if necessary, with water to obtain a solution containing about 0.1 mg of didanosine per mL. [note—Use this solution within 72 hours of preparation; because of the buffering agents in the Tablets for Oral Suspension, the Assay preparation is stable for a longer time than the Standard preparation.]
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a variable wavelength detector set at 275 nm, a 4-mm × 12.5-cm column that contains 5-µm packing L7, and a matching guard column. The flow rate is about 2.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 2000 theoretical plates; and the relative standard deviation for replicate injections is not more than 2.0%. [note—For information purposes only, the retention time of didanosine is greater than 3.0 minutes.]
Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Diluted assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg per Tablet, of didanosine (C10H12N4O3) taken by the formula:
[CVD(rU / rS)] / N
in which C is the concentration, in mg per mL, of USP Didanosine RS in the Standard preparation; V is the volume, in mL, of the Assay preparation; D is the dilution factor of the Diluted assay preparation; rU and rS are the peak responses of the Diluted assay preparation and the Standard preparation, respectively; and N is the number of Tablets for Oral Suspension used to prepare the Assay preparation.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Behnam Davani, Ph.D., M.B.A.
Senior Scientist
1-301-816-8394
(MDAA05) Monograph Development-Antivirals and Antimicrobials
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 2132
Pharmacopeial Forum: Volume No. 33(5) Page 903
Chromatographic Column—
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.