Flucytosine 50 mg/mL Oral Suspension

US Pharm. 2024;49(7):57-58.

Method of Preparation: Calculate the amount of each ingredient required for the final volume (60 mL). Open the flucytosine capsules and add contents to a mortar; then, with a pestle, triturate into a fine powder. Add a small amount of ORA-Plus and mix thoroughly to form a smooth, homogenous paste. Transfer mixture to a calibrated bottle. Gradually incorporate the remaining ORA-Plus, mixing continuously to ensure uniformity. Add ORA-Sweet or ORA-Sweet SF incrementally to a final volume of 60 mL, maintaining homogeneity and eliminating any lumps. Transfer mixture to an appropriate dispensing container and label.¹ Note: ORA-Blend, ORA-Blend SF, or other available vehicles may be used instead of those listed here.

Use: This preparation is suitable for treating serious fungal infections, including those with pulmonary involvement, such as pneumonia.

Packaging: Package in a tight, light-resistant container. Store at controlled room temperature.

Labeling: Keep out of reach of children. Shake well. Discard after ____ [time period].

Stability: The USP default beyond-use date for nonpreserved aqueous oral liquids is 14 days when stored in a refrigerator.² However, according to additional stability studies, this extemporaneous oral suspension remains stable for up to 90 days when stored at 3°C to 25°C.³

Quality Control: Weight/volume, pH, specific gravity, active drug assay, color, rheologic properties/pourability, physical observation, and physical stability (discoloration, foreign materials, gas formation, mold growth) are all examples of quality-control assessments.⁴

Discussion: Flucytosine (5-flucytosine, Ancobon, C₄H₄FN₃O, MW 129.09) is an antifungal agent indicated for the treatment of serious fungal infections, including respiratory infections, caused by certain strains of Candida and Cryptococcus. Flucytosine enters the fungal cell through the enzyme cytosine permease; once inside the cell, it is converted into 5-fluorouracil (5-FU) by another enzyme, cytosine deaminase. 5-FU interferes with fungal growth and reproduction, ultimately conquering the infection. Flucytosine is usually administered in combination with amphotericin B because of the lack of cross-resistance and the reported synergistic activity. Flucytosine occurs as a white to off-white, crystalline powder and is available in 250-mg and 500-mg capsules containing cornstarch, lactose, and talc as excipients.⁵

ORA-Plus is an oral suspending vehicle designed for extemporaneous compounding of nonsoluble, aqueous dosage preparations. It can be diluted up to 50% with water, flavoring agents, or syrups while retaining its suspending properties, making it well suited for nasogastric, pediatric, and geriatric suspensions. ORA-Plus has a slightly acidic pH of about 4.2, which helps maintain stability by reducing degradation through oxidation. This vehicle contains purified water, microcrystalline cellulose, sodium carboxymethylcellulose, xanthan gum, carrageenan, sodium phosphate, and citric acid as buffering agents, simethicone as an antifoaming agent, and potassium sorbate and methylparaben as preservatives. This blend of suspending agents creates a gel-like matrix that effectively suspends particles, minimizing settling.⁶

ORA-Sweet is a flavoring vehicle with a citrus-berry flavor that is used to enhance the palatability of oral extemporaneous preparations. It contains purified water, sucrose, glycerin, sorbitol (to prevent “cap lock”), flavoring, sodium phosphate and citric acid as buffering agents, and potassium sorbate and methylparaben as preservatives. ORA-Sweet retains its flavoring properties when diluted up to 50% with water or suspending agents, making it a flexible option for various preparations.⁷

ORA-Sweet SF is a sugar-free vehicle with a citrus-berry flavor. It contains water, sodium saccharin, xanthan gum, glycerin, sorbitol, citric acid and sodium citrate as buffers, and methylparaben, propylparaben, and potassium sorbate as preservatives.⁸

ORA-Blend, a sweetened vehicle commonly used in the compounding of oral preparations, is specifically designed to improve the taste and stability of oral suspensions. It is a synergistic blend of suspending agents with high colloidal activity that form a gel-like matrix that effectively suspends particles while minimizing settling. ORA-Blend is buffered to a slightly acidic pH, which helps minimize the oxidative degradation of medicinal agents. This vehicle also contains antifoaming agents, thereby permitting vigorous shaking with minimal foam formation, which ensures proper medication dispersion within the suspension.⁹

REFERENCES

1. Jew RK, Soo-Hoo W, Erush SC. Extemporaneous Formulations for Pediatric, Geriatric, and Special Needs Patients. 2nd ed. Bethesda, MD: American Society of Health-System Pharmacists; 2010.
2. U.S. Pharmacopeia/National Formulary [current revision]. Rockville, MD: U.S. Pharmacopeial Convention, Inc; September 2022.
3. VandenBussche HL, Johnson CE, Yun J, Patel SA. Stability of flucytosine 50 mg/mL in extemporaneous oral liquid formulations. Am J Health Syst Pharm. 2002;59(19):1853-1855.
4. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
5. Ancobon (flucytosine) product information. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; February 2019.
6. ORA-Plus product information. Minneapolis, MN: Padagis LLC; 2024.
7. ORA-Sweet product information. Minneapolis, MN: Padagis LLC; 2024.
8. ORA-Sweet SF product information. Minneapolis, MN: Padagis LLC; 2024.
9. ORA-Blend product information. Minneapolis, MN: Padagis LLC; 2024.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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