US Pharm. 2012;37(4):52-53.

Method of Preparation: Note—This formulation should be prepared according to strict aseptic compounding technique in a laminar airflow hood in a cleanroom or via isolation barrier technology by a compounding pharmacist who is validated in aseptic compounding. This is a high-risk preparation.

Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Dissolve the ondansetron hydrochloride dihydrate, sodium chloride, citric acid monohydrate, and sodium citrate dihydrate in about 90 mL of Sterile Water for Injection. Add sufficient Sterile Water for Injection to final volume and mix well. Filter through a 0.2-µg sterilizing filter into single-dose sterile vials. Package and label.

Use: Ondansetron hydrochloride injection is used in the treatment of nausea and vomiting.

Packaging: Package in tight, light-resistant containers.

Labeling: For Professional Use. Discard after ____ [time period].

Stability: If no sterility-testing program is in place, a beyond-use date of up to 24 hours may be used if the preparation is stored at controlled room temperature; 3 days if it is stored in a refrigerator; or 45 days if it is stored in solid frozen state at –25°C to –10°C or colder. If a sterility-testing program is in place, a beyond-use date of up to 6 months may be used for this preparation.1

Quality Control: Quality-control assessment can include weight/volume, physical observation, pH, specific gravity, osmolality, assay, color, clarity, particulate matter, sterility, and pyrogenicity.2,3

Discussion: Ondansetron 1 mg/mL is currently in short supply. The commercial preservative-free formula is presented here so that compounding pharmacies that are USP <797>–compliant can provide the needed medication.

Ondansetron hydrochloride (Zofran, C18H19N3O.HCl.2H2O, MW 365.85) is used as an antiemetic and as an antianxiolytic. Ondansetron hydrochloride occurs as a white to off-white powder. It is sparingly soluble in water and alcohol. Ondansetron hydrochloride should be preserved in tight, light-resistant containers at 25°C. It contains between 9.0% and 10.5% water.

Ondansetron Injection USP is a sterile solution of ondansetron hydrochloride in Water for Injection or of ondansetron in Water for Injection prepared with the aid of hydrochloric acid. It may contain suitable buffers and/or tonicity-adjusting agents. It contains an amount of ondansetron hydrochloride equivalent to not less than 95% and not more than 105% of the labeled amount of ondansetron (C18H19N3O, MW 293.36). The pH of the solution is between 3.3 and 4.0, and the solution contains not more than 9.9 USP EU per mg of ondansetron hydrochloride. One mg of ondansetron is contained in 1.25 mg ondansetron hydrochloride dihydrate.1

Sodium chloride (MW 58.44) is available as a white, crystalline powder or as colorless crystals. In parenteral preparations, it is used to prepare isotonic solutions. It is soluble in water (1 g in 2.8 mL), glycerin (1 g in 10 mL), and 95% ethanol (1 g in 250 mL).4

Citric acid (citric acid monohydrate, C6H8O7.H2O) occurs as colorless or translucent crystals or as a white, crystalline, efflorescent powder that is odorless and has a strong, tart, acidic taste. The hydrated form may contain up to 8.8% water, and the pH of a 1% w/v aqueous solution is about 2.2. One g is soluble in less than 1 mL of water and 1.5 mL of ethanol.5

Sodium citrate (trisodium citrate, C6H5Na3O7, MW 258.07, anhydrous; dihydrate, MW 294.10) occurs as colorless crystals or as a white crystalline powder. The hydrous form is freely soluble in water (1 g in 1.5 mL) and highly soluble in boiling water (1 g in 0.6 mL); it is insoluble in alcohol.1 Sodium citrate and citric acid are used to adjust the pH of solutions, as a buffer, and as a sequestering agent.6

Sterile Water for Injection is Water for Injection that has been sterilized and suitably packaged; it contains no added substances. Water for Injection is water that has been purified by distillation or reverse osmosis and contains no added substances.7

REFERENCES

1. U.S. Pharmacopeia 34/National Formulary 29. Rockville, MD: U.S. Pharmacopeial Convention, Inc; 2011:330-373,1029,3722-3726.
2. Allen LV Jr. Standard operating procedure for particulate testing for sterile products. IJPC. 1998;2:78.
3. Allen LV Jr. Standard operating procedure: quality assessment for injectable solutions. IJPC. 1999;3:406-407.
4. Maximilien JS. Sodium chloride. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. London, England: Pharmaceutical Press; 2009:637-640.
5. Amidon GE. Citric acid monohydrate. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. London, England: Pharmaceutical Press; 2009:181-183.
6. Amidon GE. Sodium citrate dihydrate. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. London, England: Pharmaceutical Press; 2009:640-642.
7. Dubash D, Shah U. Water. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. London, England: Pharmaceutical Press; 2009:766-770.

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