Didanosine Delayed-Release Capsules

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION 

Didanosine Delayed-Release Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of didanosine (C₁₀H₁₂N₄O₃)

2 IDENTIFICATION 

A. The retention time of major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

Change to read: 

B. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 197K (CN 1-May-2020) 

Sample: Empty the contents of a suitable number of Capsules, and grind to a ne powder. 

3 ASSAY 

Procedure 

Buffer: 0.77 g/L of ammonium acetate in water and pass through a suitable membrane lter of 0.45-µm pore size Mobile phase: Acetonitrile and Buffer (35:965) 

Diluent: 34.8 g/L of dibasic potassium phosphate and adjust with phosphoric acid to a pH of 7.5. Use within two weeks of preparation. Standard solution: 0.1 mg/mL of USP Didanosine RS in water 

Sample stock solution: Nominally prepare a solution at 0.6 mg/mL to 2.0 mg/mL of didanosine as follows. Mix a composite of the Capsule contents from NLT 20 Capsules in a suitable container, weigh 1 Capsule ll weight, transfer to a suitable size volumetric ask, and add 50% of the nal volume of Diluent. Stir, shake or sonicate to dissolve. Cool to room temperature, and dilute with Diluent to nal volume. 

Sample solution: Nominally 0.1 mg/mL of didanosine in Diluent from the Sample stock solution and use within 24 h Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L1 

Flow rate: 2 mL/min 

Injection volume: 20 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 1.5 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of didanosine (C₁₀H₁₂N₄O₃) in the portion of Capsules taken: 

Result = (r_u/r_s) × (C_s/C_u) × 100 

r_u = peak response of didanosine from the Sample solution 

r_s = peak response of didanosine from the Standard solution 

C_s = concentration of USP Didanosine RS in the Standard solution (mg/mL) 

C_u = nominal concentration of didanosine in the Sample solution (mg/mL) 

Acceptance criteria: 90.0%–110.0% 

4 PERFORMANCE TESTS 

4.1 Dissolution 〈711〉:

Proceed as directed for Method B under Procedure, Apparatus 1, Apparatus 2, and Delayed-Release Dosage Forms. Acid stage medium: 0.1 N hydrochloric acid; 1000 mL 

Buffer 1: 76 g/L of tribasic sodium phosphate in water 

Buffer stage medium: 0.1 N hydrochloric acid and 0.2 M tribasic sodium phosphate (3:1). Adjust with phosphoric acid or 10 N sodium hydroxide to a pH of 6.8; 1000 mL 

Buffer 2: 1.36 g/L of monobasic potassium phosphate in water 

Apparatus 1: 100 rpm 

Times 

Acid stage: 2 h 

Buffer stage: 45 min 

Mobile phase: Acetonitrile and Buffer 2 (2:98) 

Sample solution: Run the Acid stage. After the time specied, withdraw a portion of the solution under test, and pass it through a suitable lter. To the ltrate, add a volume of 10 N sodium hydroxide equivalent to 1% of the ltrate volume. Raise the basket. Discard the Acid stage medium from the vessels. Rinse the vessel with water. Add the Buffer stage medium pre-warmed to the vessel. After the time specied, withdraw a portion of the solution under test and pass it through a suitable lter. Store the acid stage and buffer stage ltrates at 5°. Standard stock solution: 0.8 mg/mL of USP Didanosine RS in water 

Didanosine related compound A standard stock solution: 0.1 mg/mL of USP Didanosine Related Compound A RS in water Standard solution: Accurately transfer portions of the Standard stock solution and the Didanosine related compound A standard stock solution to a volumetric ask, and dilute with water to volume to obtain a didanosine nal concentration of (L/1000) mg/mL where L is the Capsule label claim in mg and 0.01 mg/mL of didanosine related compound A. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 270 nm 

Column: 3.9-mm × 5-cm; 5-µm packing L7 

Flow rate: 1 mL/min 

Sample temperature: 5° Injection volume: 10 µL System suitability 

Sample: Standard solution Suitability requirements 

Tailing factor: NMT 2.0 for both the didanosine and didanosine related compound A peaks 

Relative standard deviation: NMT 2.0% for the didanosine peak and NMT 5.0% for the didanosine related compound A peak Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of didanosine as calculated based on response of didanosine related compound A released in the Acid stage: 

Result = (r_u/r_s) × (C_s/L) × D × (M_r1/M_r2) × V × 100 

Calculate the percentage of didanosine released in the Buffer stage: 

Result = (r_u/r_s) × (C_s/L) × D × V × 100  

r_u = peak response from the Sample solution. [Note—During the Acid stage, didanosine is converted to didanosine related compound A so the peak response is the hypoxanthine peak.] 

r_s = peak response from the Standard solution. [Note—During the Acid stage, didanosine is converted to didanosine related compound A so the peak response is the hypoxanthine peak.] 

C_s = concentration of USP Didanosine Related Compound A RS in the Standard solution for the Acid stage or concentration of USP Didanosine RS in the Standard solution for the Buffer stage (mg/mL) 

L = label claim (mg/Capsule) 

D = dilution factor of the Sample solution, if applicable 

M_r1 = molecular weight of didanosine, 236.2 

M_r2 = molecular weight of didanosine related compound A, 136.11 

V = volume of medium, 1000 mL 

Tolerances 

Acid stage: NMT 10% (Q) of the labeled amount of didanosine (C₁₀H₁₂N₄O₃) is dissolved in 2 h. 

Buffer stage: NLT 80% (Q) of the labeled amount of didanosine (C₁₀H₁₂N₄O₃) is dissolved in 45 min. 

4.2 Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES 

5.1 Organic Impurities 

Buffer, Mobile phase, Diluent, Sample stock solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay. System suitability solution: 0.1 mg/mL of USP Didanosine RS and 5 µg/mL of USP Didanosine Related Compound A RS in water Standard solution: 5 µg/mL of USP Didanosine Related Compound A RS in water 

System suitability 

Sample: System suitability solution 

Suitability requirements 

Tailing factor: NMT 1.5 for the didanosine peak 

Relative standard deviation: NMT 2.0% for the didanosine peak and NMT 5.0% for the didanosine related compound A peak Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of didanosine related compound A in the portion of Capsules taken: 

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of didanosine related compound A from the Sample solution 

r_s = peak response of didanosine related compound A from the Standard solution 

C_s = concentration of USP Didanosine Related Compound A RS in the Standard solution (mg/mL) 

C_u = nominal concentration of didanosine in the Sample solution (mg/mL) 

Calculate the percentage of any unspecied impurities in the portion of Capsules taken: 

Result = (r_X/r_SUM) × 100 

r_X = peak response of each impurity from the Sample solution 

r_SUM = peak response of all peaks from the Sample solution 

Acceptance criteria: See Table 1. 

Table 1 

a Hypoxanthine. 

6 SPECIFIC TESTS 

Microbial Enumeration Tests 〈61〉and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count is not more than 102 cfu/g. The total yeasts and molds count is not more than 102 cfu/g. 

7 ADDITIONAL REQUIREMENTS 

Packaging and Storage:

Preserve in well-closed containers, and store at controlled room temperature. 

7.1 USP Reference Standards 〈11〉 

USP Didanosine RS 

USP Didanosine Related Compound A RS 

6-Hydroxypurine (Hypoxanthine). 

C₅H₄N₄O             136.11