Doxycycline Hyclate 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)

DOWNLOAD PDF HERE

1 DEFINITION

Doxycycline Hyclate Delayed-Release Capsules contain the equivalent of NLT 90.0% and NMT 120.0% of the labeled amount of doxycycline (C₂₂H₂₄N₂O₈).

2 IDENTIFICATION

A.

Test solution: Nominally 1 mg/mL of doxycycline in methanol from finely powdered Capsule contents. Pass through a filter, and use the filtrate.

Analysis: Proceed as directed in Identification-Tetracyclines (193), Method II.

Acceptance criteria: Meets the requirements

3 ASSAY

PROCEDURE

Mobile phase: Transfer 2.72 g of monobasic potassium phosphate, 0.74 g of sodium hydroxide, 0.50 g of tetrabutylammonium hydrogen sulfate, and 0.40 g of edetate disodium to a 1000-mL volumetric flask. Add 850 mL of water, and stir to dissolve. Add 60 g of tertiary butyl alcohol with the aid of water, dilute with water to volume, and adjust with 1 N sodium hydroxide to a pH of 8.0 ± 0.1. Pass this solution through a filter of 0.5-µm or finer pore size, and degas before using. Decreasing the proportion of tertiary butyl alcohol results in a longer retention time of doxycycline and improved separation of doxycycline from the related compounds.

Diluent: 0.01 N hydrochloric acid

System suitability stock solution: 6 mg/mL of doxycycline from USP Doxycycline Hyclate RS in Diluent

System suitability solution: Transfer 5 mL of System suitability stock solution to a 25-mL volumetric flask, heat on a steam bath for 60 min, and evaporate to dryness on a hot plate, taking care not to char the residue. Dissolve the residue in 0.01 N hydrochloric acid, and dilute with Diluent to volume. Pass a portion of this solution through a filter of 0.5-µm or finer pore size, and use the filtrate. This solution contains a mixture of 4-epidoxycycline, 6-epidoxycycline, and doxycycline. When stored in a refrigerator, this solution may be used for 14 days.

Standard solution: 1.2 mg/ml. of USP Doxycycline Hyclate RS in Diluent. Sonicate as needed to dissolve. Protect the Standard solution from light.

Sample solution: Nominally 1 mg/mL of doxycycline in Diluent, prepared as follows. Remove as completely as possible the contents of NLT 20 Capsules. Mix the combined contents, and transfer a suitable portion of the powder to a suitable volumetric flask. Add 75% of the final volume of Diluent, sonicate for 5 min, shake for 15 min, and dilute with Diluent to volume. Pass through a membrane filter of 0.5-µm or finer

pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 270 nm.

Column: 4.6-mm x 25-cm; packing L21

Column temperature: 60 ± 1°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: 1.7 times the retention time of doxycycline

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for 4-epidoxycycline (the main degradation product), 6-epidoxycycline, and doxycycline are about 0.4, 0.7,

and 1.0, respectively, System suitability solution.]

Suitability requirements

Resolution: NLT 3.0 between the 4-epidoxycycline peak and the doxycycline peak, System suitability solution

Tailing factor: NMT 2.0 for doxycycline, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of doxycycline (C₂H₂ NO) in the portion of Capsules taken:

Result = (r_U/(r_S) × (C_S /C_U) × P x F x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Doxycycline Hyclate RS, in the Stardard solution (mg/ml)

C_U = nominal concentration of doxycycline in the Sample sulation (mg/ml)

P = potency of doxycycline in USP Doxycycline Hyclate RS (µg/mg)

F = conversion factor 0.001 mg/μg

Acceptance criteria: 90.0%-120.0%

4 PERFORMANCE TESTS

DISSOLUTION (711): Proceed as directed for Apparatus 1 and Apparatus 2. Delayed-Release Dosage Forms, Method B. Procedure.

Acid stage

Conduct the test by transferring the contents of each Capsule to the individual basket units of the apparatus.

Medium: 0.06 N hydrochloric acid; 900 mL

Apparatus 1: 50 rpm

Time: 20 min

Detector: UV 345 nm

Diluent: 0.1 N hydrochloric acid

Standard solution: 10 µg/mL of USP Doxycycline Hyclate RS in Diluent

Sample solution: Dilute filtered portions of the solution under test with Diluent to a concentration that is similar to the Standard solution.

Tolerances

Level 1 (6 Capsules tested): No individual value exceeds 50% dissolved.

Level 2 (6 Capsules tested): NMT 2 individual values of 12 tested are greater than 50% dissolved.

Buffer stage

Conduct this stage of testing on separate specimens, selecting Capsules that were not previously subjected to Acid stage testing and

transferring the contents of each Capsule to the individual basket units of the apparatus.

Medium: pH 5.5 neutralized phthalate buffer (see Reagents, Indicators, and Solutions-Buffer Solutions-Buffer Solutions); 1000 ml.

Apparatus 1: 50 rpm.

Time: 30 min

Detector: UV 345 nm

Diluent: 0.1 N hydrochloric acid

Standard solution: 10 µg/mL of USP Doxycycline Hyclate RS in Diluent

Sample solution: Dilute filtered portions of the solution under test with Diluent to a concentration that is similar to the Standard solution.

Tolerances: NLT 85% (Q) of the labeled amount of doxycycline (CH, NO) is dissolved.

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

SPECIFIC TESTS

WATER DETERMINATION, Method /(921): NMT 5.0%

5 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers.

LABELING: The label indicates that the contents of the Capsules are enteric coated.