Doxycycline for Oral Suspension

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

Doxycycline for Oral Suspension contains the equivalent of NLT 90.0% and NMT 125.0% of the labeled amount of doxycycline (C₂₂H₂₄N₂O₈) when constituted as directed. It contains one or more suitable buffers, colors, diluents, flavors, and preservatives.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopyc 197A

Standard: Transfer about 25 mg of USP Doxycycline Monohydrate RS to a suitable flask. Add 25 ml of acetonitrile and mix for approximately 10 min with a magnetic stir bar. Pass through suitable filter paper (Whatman #40 or equivalent), and remove the solvent by natural evaporation.

Sample: Place an amount of Doxycycline for Oral Suspension, nominally equivalent to about 25 mg of doxycycline, in a suitable flask. Add 25 ml of acetonitrile and mix for approximately 10 min with a magnetic stir bar. Pass through suitable filter paper (Whatman #40 or equivalent), and remove the solvent by natural evaporation.

Analysis: Examine the spectra of the Standard and the Sample in the range between 2000 and 650c * m ^ - 1

Acceptance criteria: The Sample exhibits bands at about 1644, 1577, 1518, 1452, 1396, 1167, 995, and 952c * m ^ - 1 similar to the Standard.

[NOTE-Peak positions may vary slightly (within plus/minus 10 * c * m ^ - 1 ) Other peaks may be present in the spectra that do not appear in this list.) (USP 1-Aug-2023)

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

3 ASSAY

Change to read:

PROCEDURE

Protect solutions containing doxycycline from light

Solution B: Methanol

Mobile phase: See Table 1.

Diluent: 0.01 N hydrochloric acid

Standard solution: 0.3 mg/mL of USP Doxycycline Hyclate RS in Diluent. Sonicate as needed to dissolve.

Sample solution: Nominally 0.25 mg/mL of doxycycline in Diluent, prepared as follows, Constitute Doxycycline for Oral Suspension as directed in the labeling. Transfer an accurately measured portion of the constituted suspension, freshly mixed and free from air bubbles, equivalent to about 25 mg of doxycycline, to a suitable volumetric flask. Add 50% of the final volume of Diluent, shake by mechanical means for about 15 min and dilute with Diluent to volume. Pass a portion of this solution through a suitable filter of 0.2-um pore size.

Chromatographic system

(See Chromatography (621). System Suitability)

Mode: LC

Detector: UV 350 nm

Column: 2.1-mm 5-cm, 1.7-um packing 17 [NOTE-A 1.7-um guard column with packing 17 was used during method validation.]

Column temperature: 60°

Flow rate: 0.6 mL/min

Injection volume: 5 µl

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0% (USP 1-Aug-2023)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of doxycycline (CHNO) in the portion of Doxycycline for Oral Suspension taken:

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

r_U = peak response of doxycycline from the Sample solution

r_S = peak response of doxycycline 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%~125.0%

4 PERFORMANCE TESTS

Change to read:

DISSOLUTION (711)

Protect solutions containing doxycycline from light

Medium: 0.01. N hydrochloric acid: 900 mL

Apparatus 2: 25 rpm

Time: 10 min

OFFICIA Solution A: Transfer 1.36 g of monobasic potassium phosphate, 0.37 g of sodium hydroxide, 0.25 g of tetrabutylammonium hydrogen sulfate. and 0.2 g of edetate disodium to a 1000 ml volumetric flask. Add about 850 ml of water and mix. Add 75 g of tert-butyl alcohol and dilute with water to volume. Adjust with 1 N. sodium hydroxide or 5 N hydrochloric acid to a pH of 8.0 ±0.05.

Solution B: Acetonitrile and water (80:20)

Mobile phase: See Table 2.

Standard solution: 32 µg/mL of USP Doxycycline Hyclate RS in Medium

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USP-NF Doxycycline for Oral Suspension

Sample solution: Reconstitute the suspension according to the label instructions for three separate containers. Transfer and combine the contents of the three containers into a separate suitable flask. Determine the density of the suspension. Using suitable syringes, measure portions of the reconstituted suspension containing nominally 25 mg of doxycycline. With the paddles lowered, gently empty the contents of each syringe into each vessel containing Medium. Start the paddle rotation. At the specified time, withdraw the solution under test

(USP 1-Aug-2023) and pass a portion through a suitable filter of 0.45-um pore size.

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

Detector: UV 355 nm

Column: 4.6-mm x 25-cm, 5-um packing 121

Temperatures

Autosampler: 10°

Column: 60°

Flow rate: 1.5 mL/min

Injection volume: 100 µL

System suitability

Sample: Standard solution

Suitability requirements.

Tailing factor: NMT 2.0 Relative standard deviation: NMT 2.0% Analysis Samples: Standard solution and Sample solution Calculate the percentage of the labeled amount of doxycycline (C H N O ) dissolved:

Result = (r_U/(r_S) × C_S × (1/L) × (d/W) × V × P × F × 100

r_U = peak response of doxycycline from the Sample solution

r_S = peak response of doxycycline from the Standard solution

C_S = concentration of doxycycline in the Standard solution (mg/mL)

L = label claim of Doxycycline for Oral Suspension (mg/5 mL)

d = density of the Sample solution (g/mL)

W = weight of Doxycycline for Oral Suspension taken (g)

V = volume of Medium, 900 mL

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

F = conversion factor, 0.001 mg/µg

Tolerances: NLT 80% (Q) of the labeled amount of doxycycline (C₂₂H₂₄N₂O₈) is dissolved.

DELIVERABLE VOLUME (698): Meets the requirements

UNIFORMITY OF DOSAGE UNITS (905)

For single-unit containers

Acceptance criteria: Meets the requirements

IMPURITIES

Change to read:

ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

System suitability stock solution 1: 1 mg/ml each of USP Doxycycline Related Compound A RS and USP Methacycline Hydrochloride RS in Diluent

System suitability stock solution 2: 1.2 mg/ml, of USP Doxycycline Hyclate RS in Diluent

System suitability solution: Transfer 5 mL of System suitability stock solution 2 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 Diluent, add 0.5 mL. of System suitability stock solution 1, and dilute with Diluent to volume. Pass the solution through a suitable filter and use the filtrate. This solution contains a

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USP-NF Doxycycline for Oral Suspension

mixture of 4-epidoxycycline, doxycycline related compound A, methacycline, and doxycycline. When stored in a refrigerator, this solution.

may be used for 14 days.

Standard solution: 1.5 µg/mL of USP Doxycycline Hyclate RS in Diluent

Sample solution: Nominally, a 0.25-mg/mL solution of doxycycline in Diluent is prepared as follows. Constitute Doxycycline for Oral Suspension as directed in the labeling. Transfer an accurately measured portion, freshly mixed and free from air bubbles, equivalent to about 25 mg of doxycycline, to a 100-ml volumetric flask. Add 50 mL of Diluent and shake by mechanical means for about 15 min. Dilute with Diluent to volume. Pass a portion of this solution through a suitable filter of 0.2-um pore size.

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between methacycline and 4-epidoxycycline, NLT 1.5 between 4-epidoxycycline and doxycycline related compound A;

and NLT 2.0 between doxycycline related compound A and doxycycline, System suitability solution

Relative standard deviation: NMT 5.0% for the doxycycline peak, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Doxycycline for Oral Suspension taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of doxycycline 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: See Table 3. The reporting threshold is (USP 1-Aug-2023) 0.1%

^a (4S,4aR,55,5aR, 12aS)-4-(Dimethylamino)-1,4,4,5,58,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methylene-1,11-dioxo-2-naphthacenecarboxamide.

^b (4R,4aR,55,5aR,6,12aS)-4-(Dimethylamino)-1,4,4,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide.

^c(4R,4aR,5S,5aR,6R,12aS)-4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2- naphthacenecarboxamide.

^d (4S,4aR,5S,5aR,6S,12aS)-4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2- naphthacenecarboxamide.

5 SPECIFIC TESTS

PH (791)

Sample solution: Constitute as directed in the labeling.

Acceptance criteria: 5.0-6.5

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6 ADDITIONAL REQUIREMENTS

USP-NF Doxycycline for Oral Suspension

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store dry powder at controlled room temperature.