US Pharm. 2013;38(4):36-37.
Method of Preparation: Calculate the required quantity of each ingredient for the total amount to be prepared. Accurately weigh or measure each ingredient. Dissolve the caffeine citrate, potassium sorbate, sodium citrate, and sorbitol (if used) in about 90 mL of Sterile Water for Injection. Add sufficient Sterile Water for Injection to volume and mix well. Filter through a sterilizing filter into sterile containers; package and label.
Use: Caffeine has been used as a respiratory stimulant in neonates.
Packaging: Package this preparation in sterile, tight, light-resistant containers.1
Labeling: Keep out of reach of children. Use only as directed.
Stability: If this preparation is sterility tested, a beyond-use date of up to 6 months at either room temperature or refrigerated temperature may be used.1,2
Quality Control: Quality-control assessment can include weight/volume, pH, specific gravity, active drug assay, sterility, color, rheologic properties/pourability, physical observation, and physical stability (discoloration, foreign materials, gas formation, mold growth).3
Discussion: Caffeine citrate oral solution is currently listed in short supply. This preparation, as well as many others, may be compounded during such periods to continue the supply of medication to patients.
Caffeine citrate (C8H10N4O2.C6H8O7, MW 386.3) is a white powder with a bitter taste. It is obtained by combining caffeine with citric acid. Caffeine citrate is freely soluble in water and soluble in alcohol. Caffeine, anhydrous (C8H10N4O2, MW 194.19), occurs as a white powder or as white, glistening needles, usually matted together. The percentage of caffeine in caffeine citrate is about 50% (MW ratio: 194.19/386.3 = 50.3%); it is important to confirm whether the prescribed dosage calls for caffeine or for caffeine citrate. Caffeine, a xanthine derivative, is a central nervous system stimulant. It occurs naturally in tea and coffee, but is synthetically prepared for pharmaceutical use. It is used orally and IV to treat apnea of prematurity. For oral administration, the dose should be accurately measured and delivered.4
Caffeine citrate oral solution, USP, is a sterile aqueous solution containing caffeine and citric acid. It contains not less than 90.0% and not more than 110.0% of the labeled amount of caffeine citrate (C14H18N4O9). It contains no bacteriostat or other preservative. The pH of the solution is between 4.2 and 5.2, and it meets the requirements when tested as directed for “Membrane Filtration” under “Test for Sterility of the Product to Be Examined.”1
Potassium sorbate (C6H7O2K, MW 150.22) occurs as a white, crystalline powder with a faint, characteristic odor. It is used as an antimicrobial (antifungal and antibacterial) preservative. It is soluble in water (1 g in 1.72 mL), acetone (1 g in 1,000 mL), 95% alcohol (1 g in 35 mL), and propylene glycol (1 g in 1.8 mL). Potassium sorbate is most effective at pH values of approximately 6 and below; it loses significant efficacy above pH 6. Although its antimicrobial properties are somewhat less than those of sorbic acid, potassium sorbate is used in more products because of its greater water solubility.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 very soluble in boiling water (1 g in 0.6 mL); it is insoluble in alcohol. Sodium citrate is used to adjust the pH of solutions and also as a sequestering agent.6
Sorbitol (D-glucitol, C6H14O6, MW 182.17) is a hexahydric alcohol related to mannose; it is isomeric with mannitol. It occurs as an odorless, white or almost colorless, crystalline powder. Sorbitol has a pleasant, cooling, sweet taste and is approximately 50% to 60% as sweet as sucrose. The pH of a 10% w/v aqueous solution is in the range of 4.5 to 7.0. Sorbitol melts at about 110°C to 112°C. It is a highly hygroscopic powder and should be stored in tight containers.7
1. U.S. Pharmacopeia 35/National Formulary 30. Rockville, MD: U.S. Pharmacopeial Convention, Inc; 2012:2429.
2. Barnes AR, Hebron BS, Smith J. Stability of caffeine oral formulations for neonatal use. J Clin Pharm Ther. 1994;19:391-396.
3. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
4. McEvoy GK, ed. AHFS Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists; 2011:2588-2592.
5. Boxell KE. Potassium sorbate. In: Rowe RC, Sheskey PJ, Cook WG, Fenton ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:659-660.
6. Amidon GE. Sodium citrate dihydrate. In: Rowe RC, Sheskey PJ, Cook WG, Fenton ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:732-734.
7. Shur J. Sorbitol. In: Rowe RC, Sheskey PJ, Cook WG, Fenton ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:776-779.
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