Doxycycline Compounded Oral Suspension, Veterinary

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

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Doxycycline Compounded Oral Suspension, Veterinary contains NLT 90.0% and NMT 110.0% of the labeled amount of doxycycline (C₂₂H₂₄N₂O₄) Prepare Oral Suspension, Veterinary 50 mg/mL in a paraben solution (USP 1-May-2020) as follows (see Pharmaceutical Compounding-Nonsterile Preparations (795)). For this preparation, a Paraben solution needs to be separately prepared.

Prepare a Paraben solution by dissolving the Methylparaben and Propylparaben in a sufficient amount of Purified Water to bring to final volume.

^a Calculate the amount of Doxycycline Hyclate powder required by dividing the weight of doxycycline required by the potency of the Doxycycline Hyclate powder obtained from the Certificate of Analysis. [NOTE-Unit conversion is needed in the calculation. (USP 1-May-2020)

^b Calculate the amount of Calcium Hydroxide needed, in grams, by multiplying the amount of Doxycycline Hyclate needed, in grams, by 0.21.

Pour the calculated amount of Doxycycline Hyclate powder into a suitable mortar, and mix with about 12.5 mL of Paraben solution until all the solids are dissolved. Do not use more than 5 mL of Paraben solution for each gram of the calculated amount of Doxycycline Hyclate. Add the calculated amount of Calcium Hydroxide to the mortar, and mix with the pestle until the mixture thickens up and has a pasty consistency. [NOTE-Reaction may take a few minutes to occur. The pasty mixture may look dry and harden up which is an indication that the reaction is complete.]

In a separate beaker, mix Glycerin and Polysorbate 20 with about 30 ml of the Paraben solution. Add Sodium Metabisulfite to the mixture of Glycerin, Polysorbate 20, and Paraben solution with mixing.

Add approximately two thirds of the separately prepared mixture of Glycerin, Polysorbate 20, Sodium Metabisulfite, and Paraben solution to the mortar in small increments with continuous mixing to make an even mixture free of lumps. Transfer the doxycycline mixture from the mortar to an appropriately sized beaker. Rinse the mortar three times, each time with one third of the remaining Glycerin, Polysorbate 20, Sodium Metabisulfite, and Paraben solution, and combine with the doxycycline mixture in the beaker. Add Steviol Glycosides 95% to the beaker.

Disperse Carboxymethylcellulose Sodium through a 40-mesh sieve, and mix into the suspension until homogenous. Add sufficient Paraben solution to bring to final volume. Mix well.

Prepare Oral Suspension, Veterinary 100 mg/ml. in a fixed oil base as follows (see Pharmaceutical Compounding-Nonsterile Preparations (795)

^a Calculate the amount of Doxycycline Hyciate powder required by dividing the weight of doxycycline required by the potency of the Doxycycline ryclate powder obtained from the Certificate of Analysis. (Norz Unit conversion is needed in the calculation.]

b PCCA, Houston, TX.

Place the calculated amount of Doxycycline Hyciate powder, Steviol Glycosides 95%, and Acesulfame Potassium into a suitable container and triturate to a fine powder. Add a sufficient amount of PCCA Fixed Oil Suspension Vehicle to form a smooth paste. Add Flavor and mix thoroughly. Add a sufficient amount of PCCA Fixed Oil Suspension Vehicle to make the contents pourable. Transfer the contents, stepwise and quantitatively, to a calibrated container using the PCCA Fixed Oil Suspension Vehicle. Add sufficient PCCA Fixed Oil Suspension Vehicle to

bring to final volume, and mix well.

2 ASSAY

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PROCEDURE 1: ORAL SUSPENSION IN PARABEN SOLUTION (USP 1 MW-2020)

Solution A: 20 mM monobasic sodium phosphate containing 0.74 g/L of sodium hydroxide. Adjust with phosphoric acid to a pH of 7.0.

Mobile phase: See Table 1

Diluent: Acetonitrile and 1 N hydrochloric acid (50:50)

Standard solution: 0.5 mg/mL of doxycycline prepared from USP Doxycycline Hyclate RS in Diluent

Sample solution: Shake each bottle of Oral Suspension, Veterinary thoroughly. Transfer 0.5 ml. of Oral Suspension, Veterinary to a 50-ml volumetric flask, add approximately 10 mL of Diluent, and vortex for 30 s. Dilute with Diluent to volume, and mix well

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

Detector: UV 270 nm

Column: 3.9-mm x 15-cm, 5-µm packing L1

Column temperature: 40

Flow rate: 1.0 mL/min

Injection volume: 5 μ

System suitability

Sample: Standard solution

NOTE-The retention time for doxycycline is about 4.7 min]

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of doxycycline (C₂₂H₂₄N₂O₄) in the portion of Oral Suspension, Veterinary taken:

Result = (r_U/(r_S) × (C_S /C_U) 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 doxycycline in the Stardard solution (mg/ml)

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

Acceptance criteria: 90% - 110%

Add the following:

PROCEDURE 2: ORAL SUSPENSION FIXED OIL

Solution A: 1 mg/mL of triuoroacetic acid in water

Solution B: 1 mg/mL of triuoroacetic acid in acetonitrile

Mobile phase: See Table 2

Standard solution: 0.125 mg/mL of doxycycline prepared from USP Doxycycline Hiclate RS in methanol

Sample solution: Transfer 0.5 mL of Oral Suspension, Veterinary to a centrifuge tube and add 39.5 mL of methanol. Vortex for 1 min, sonicate for 2 min, and vortex again for 1 min until the solution is mixed well. Centrifuge this solution for 10 min. Transfer 1 mL of the supernatant to a 10-mL volumetric flask and add sufficient methanol to bring to volume. Centrifuge again for 10 min.

Chromatographic system

(See Chromatography/621) System Suitability)

Mode: LC

Detector: UV 350 nm

Column: 2.1mm x 50-mm, 1.7-um packing L1

Autosampler temperature: 4

Flow rate: 0.7 mL/min

Injection volume: 1.0 µL

System suitability

Sample: Standard solution

Nor-The retention time for doxycycline is about 2.7 min.

Suitability requirements

Relative standard deviation: NMT 2.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of doxycycline (C₂₂H₂₄N₂O₄) in the portion of Oral Suspension, Veterinary taken:

Result = (r_U/(r_S) × (C_S /C_U) 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 doxycycline in the Stardard solution (mg/ml)

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

Acceptance criteria: 90.0%-110.0% 

3 SPECIFIC TESTS

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H(791)

*Oral Suspension in paraben solution: 

6.0-7.0

4 ADDITIONAL REQUIREMENTS

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PACKAGING AND STORAGE: Package in tight, light-resistant containers. Store the Oral Suspension, Veterinary in paraben solution in a refrigerator.

Store the Oral Suspension, Veterinary in fixed oil at controlled room temperature, or in a refrigerator

LABEUNG: Label it to indicate that it is to be well shaken before use, and to state the Beyond-Use Date. Label it to state that it is for veterinary use only.

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BEYOND-USS DATE

*Oral Suspension, Veterinary in paraben solution: NMT 30 days after the date on which it was compounded when stored in a refrigerator Oral Suspension, Veterinary in fixed oil: NMT 60 days after the date on which it was compounded when stored at controlled room

temperature or in a refrigerator