US Pharm. 2009;34(5):48-49.
Method of Preparation: Note: This preparation should be compounded in a laminar airflow hood in a cleanroom or via isolation barrier technology by a validated aseptic compounding pharmacist using strict aseptic technique. This is a high-risk preparation.
Calculate the required quantity of each ingredient for the total amount to be prepared. Accurately weigh or measure each ingredient. Dissolve the sodium naproxen in about 40 mL of Sterile Water for Injection. Add the propylene glycol and benzyl alcohol, and mix well. Adjust the pH to the range of 7.5 to 8.5. Add sufficient Sterile Water for Injection to volume, and mix well. Filter the mixture through a sterile 0.22-micron filter into sterile vials. Package and label.
Use: Naproxen sodium injection has been used in cases in which an injectable nonsteroidal anti-inflammatory drug is needed.
Packaging: Package in tight, light-resistant containers.1
Labeling: Keep out of the reach of children. Use only as directed.
Stability: If not sterility-tested: A beyond-use date of up to 24 hours at room temperature, up to 3 days at refrigerated temperature (2°C to 8°C), or up to 45 days if frozen can be used for this preparation.1
If sterility-tested: A beyond-use date of up to 14 days can be used when this preparation is stored in a refrigerator.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: Naproxen, a propionic-acid derivative, is a prototypical nonsteroidal anti-inflammatory agent. It is structurally and pharmacologically related to fenoprofen and ibuprofen. Naproxen is used to treat musculoskeletal and joint disorders and for headache, including migraine headaches.
Naproxen sodium (C14H13NaO3, MW 252.24) occurs as a white to cream-colored crystalline powder. It is soluble in water and sparingly soluble in alcohol. It melts at about 255°C, with decomposition. About 550 mg of naproxen sodium is equivalent to 500 mg of naproxen.1,4
Propylene glycol (C3H8O2) occurs as a clear, colorless, viscous, practically odorless liquid with a sweet taste, somewhat resembling glycerin. It has a specific gravity of 1.038 g/mL and is miscible with acetone, chloroform, 95% ethanol, glycerin, and water. Propylene glycol is not miscible with fixed oils or with light mineral oil. It will, however, dissolve some essential oils.5
Benzyl alcohol (C7H8O, MW 108.14) is an antimicrobial preservative, disinfectant, and solvent. It should not be used in preparations that are administered to neonates. Benzyl alcohol is a clear, colorless, oily liquid that has a faint, aromatic odor and a sharp, burning taste. It is soluble 1 g in 25 mL of water at 25°C, and it is miscible with ethanol.6
Hydrochloric acid (HCl, MW 36.46) occurs as a clear, colorless, fuming aqueous solution of hydrogen chloride that has a pungent odor. It is miscible with water and is soluble in ethanol. The pH of a 10% v/v aqueous solution is 0.1. Hydrochloric acid should be stored in well-closed glass or other inert containers.7
Sodium hydroxide (NaOH, MW 40.00, caustic soda, soda lye) occurs as dry, very deliquescent, white or almost white sticks, pellets, or fused masses that are hard and brittle. It is soluble 1 g in 1 mL of water and is freely soluble in alcohol. Sodium hydroxide should be stored in airtight, nonmetallic containers.8
REFERENCES
1. US Pharmacopeial Convention, Inc. USP 32/NF 27. Rockville, MD: US Pharmacopeial Convention, Inc; 2009:314-354,895,911,919,928,
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. Sweetman SC, ed. Martindale: The Complete Drug Reference. 36th ed. London, England: Pharmaceutical Press; 2009:92-94.
5. Weller PJ. Propylene glycol. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: American Pharmaceutical Association; 2005:624-626.
6. Cahill E. Benzyl alcohol. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: American Pharmaceutical Association; 2006:69-71.
7. Owen SC. Hydrochloric acid. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: American Pharmaceutical Association; 2005:328-329.
8. Kibbe AH. Sodium hydroxide. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: American Pharmaceutical Association; 2005:683-684.
