US Pharm. 2019;44(4):Epub.
Method of Preparation: Hold the neck of the bottle containing the omeprazole powder and tap the bottom edges on a hard surface to loosen the powder. Remove the cap from the bottle. Tap the top of the induction seal liner to loosen any powder adhering to the liner. Carefully and slowly peel back the inner foil seal liner from the bottle. Using the enclosed tool, scrape any omeprazole powder from the seal into the bottle. Using the smaller end of the tool, with firm strength loosen any powder from the inside lower edges of the bottle. It is important to ensure that no omeprazole powder remains trapped in the inside lower edges of the bottle. Again using the tool, distribute the omeprazole powder evenly over the bottom surface of the bottle. Shake the FIRST-PPI Suspension bottle for a few seconds. Open the FIRST-PPI Suspension bottle and empty about one-half of its contents into the omeprazole powder bottle. Replace the cap and shake the omeprazole powder bottle for approximately 60 seconds. Shake vigorously. Empty the remaining FIRST-PPI Suspension into the omeprazole powder bottle. Allow the suspension to drain for 10 seconds. Replace the cap and shake the omeprazole powder bottle vigorously for approximately 30 seconds.
Note: As appropriate, dispense the enclosed adapter cap and oral syringe with accompanied instructions for use. Instruct the patient in the use of the suspension with the enclosed adapter cap and oral syringe. The adapter cap is not child resistant.
Use: Omeprazole is a proton pump inhibitor used in the treatment of gastric hyperacidity.
Packaging: Package in the containers in which it is provided and compounded.
Labeling: Keep out of reach of children. Protect from light. Protect from freezing. Shake well before each use. Refrigerate. Discard after ____ [time period].
Stability: A beyond-use date of not more than 30 days when stored at refrigerated temperature may be used.1,2
Quality Control: Quality-control assessment can include weight/volume, pH, specific gravity, active drug assay, color, rheologic properties/pourability, physical observation, and physical stability (discoloration, foreign materials, gas formation, mold growth).3
Discussion: Omeprazole (Prilosec, C17H19N3O3S, MW 345.42) occurs as a white to off-white powder that melts with decomposition at about 155°C; it is a weak base. Omeprazole is very slightly soluble in water (1 g in 8,000 mL) and is sparingly soluble in alcohol (1 g in 25 mL). Omeprazole’s degradation rate increases with decreasing acidic pH values, but it has acceptable stability under alkaline conditions. Commercial solid oral products are available that may or may not be suitable for patients.4
Also available is a FIRST-Omeprazole Compounding Kit that is comprised of omeprazole powder USP and FIRST-PPI (proton pump inhibitor) Suspension containing artificial strawberry flavor, benzyl alcohol, FD&C Red #40, Magnasweet 100 (ammonium glycyrrhizate), poloxamer 188, propylene glycol, purified water, simethicone emulsion, sodium bicarbonate, sodium citrate (dihydrate), sucralose, and xanthan gum. When compounded, the final product provides a homogenous suspension containing 2 mg per mL of omeprazole in FIRST-PPI Suspension comparable to the active ingredient in Simplified Omeprazole Suspension.2
A typical artificial strawberry flavor may contain the following ingredients: amyl acetate, amyl butyrate, amyl valerate, anethol, anisyl formate, benzyl acetate, benzyl isobutyrate, butyric acid, cinnamyl isobutyrate, cinnamyl valerate, cognac essential oil, diacetyl, dipropyl ketone, ethyl acetate, ethyl amyl ketone, ethyl butyrate, ethyl cinnamate, ethyl heptanoate, ethyl heptylate, ethyl lactate, ethyl methylphenylglycidate, ethyl nitrate, ethyl propionate, ethyl valerate, heliotropin, hydroxyphenyl-2-butanone (10% solution in alcohol), alpha-ionone, isobutyl anthranilate, isobutyl butyrate, lemon essential oil, maltol, 4-methylacetophenone, methyl anthranilate, methyl benzoate, methyl cinnamate, methyl heptine carbonate, methyl naphthyl ketone, methyl salicylate, mint essential oil, neroli essential oil, nerolin, neryl isobutyrate, orris butter, phenethyl alcohol, rose, rum ether, gamma-undecalactone, vanillin, and solvent.5
Benzyl alcohol (C7H8O, MW 108.14) is an antimicrobial preservative, disinfectant, and solvent. As an antimicrobial preservative, it is commonly used in concentrations up to 2% in pharmaceutical formulations. 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 and is miscible with ethanol.6
FD&C Red #40 (C18H14N2Na2O8S2 496.42 g·mol–1, Allura Red AC, FD&C Red 40, E129, disodium 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfonatophenyl)diazenyl]naphthalene-2-sulfonate, Food Red 17) is a red azo dye that occurs as a red powder with a melting point of 300°C. It is usually supplied as its red sodium salt, but the calcium and potassium salts may also be used. These salts are soluble in water. In solution, its maximum absorbance lies at about 504 nm. Allura Red AC is a popular dye used worldwide; annual production in 1980 exceeded 2.3 million kg.7
Magnasweet (ammonium glycyrrhizate, C42H65NO16-anhydrous MW 840.08; C42H65NO16.5H2O-pentahydrate, MW 930.04) occurs as a white to yellowish-white or brown, hygroscopic powder with an intensely sweet taste. It is used as a sweetening, flavoring, taste-masking, and emulsifying agent. Magnasweet is slightly soluble in water and very slightly soluble in anhydrous ethanol.8
Poloxamer 188 is a block copolymer of ethylene oxide and propylene oxide that occurs as white-colored, waxy, free-flowing granules that are practically odorless and tasteless. The poloxamers are used as emulsifying, solubilizing, and wetting agents. The poloxamers are stable, and aqueous solutions are stable in the presence of acids, alkalis, and metal ions. Poloxamer 188 is freely soluble in water and alcohol.9
Propylene glycol (C3H8O2) occurs as a clear, colorless, viscous, hygroscopic, practically odorless liquid with a sweet taste somewhat resembling glycerin. It is miscible with acetone, chloroform, 95% ethanol, glycerin, and water.10
Purified water is water that is obtained by distillation, ion exchange, reverse osmosis, or some other suitable process. Water has a specific gravity of 0.9971 at room temperature, a melting point of 0°C, and a boiling point of 100°C. It is miscible with most polar solvents and is chemically stable in all physical states (ice, liquid, and steam).11
Simethicone {CH3[Si(CH3)2.O]nSi(CH3)3, dimethyl silicone fluid, poly(dimethylsiloxane)} is a fluid silicone that occurs as a clear, colorless, odorless liquid that is insoluble in water, alcohol, acetone, and methyl alcohol.12
Sodium bicarbonate (baking soda, sal de Vichy, NaHCO3, MW 84.01) occurs as a white, crystalline powder that is stable in dry air, but it slowly decomposes in moist air. It is soluble in water (1 g in 10-12 mL) but insoluble in alcohol.1,13
Sodium citrate dihydrate (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.14
Sucralose (Unisweet, C12H19Cl3O8, MW 397.64) occurs as a white to off-white, free-flowing, crystalline powder. It is freely soluble in ethanol (95%) and in water (0.283 g/mL). Its sweetening power is about 300 to 1,000 times that of sucrose, and it has no aftertaste.15
Xanthan gum (corn sugar gum) is a high-molecular-weight polysaccharide gum. It occurs as a cream-colored or white, odorless, free-flowing fine powder that is soluble in cold or warm water but is practically insoluble in ethanol and ether. Xanthan gum is used as a stabilizing agent and as a viscosity-increasing agent in suspensions. It is nontoxic, is compatible with most other excipients, and has good stability (in the presence of enzymes, salts, acids, and bases) and viscosity properties over a wide range (pH 3-12).16
REFERENCES
1. U.S. Pharmacopeia/National Formulary [current revision]. Rockville, MD: U.S. Pharmacopeial Convention, Inc; April 2019.
2. FIRST-Omeprazole package insert. Wilmington, MA: Cutis Pharma; October 2016.
3. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
4. Allen LV Jr., ed. Remington: The Science and Practice of Pharmacy. 22nd ed. London, England: Pharmaceutical Press; 2013:1634-1635.
5. Artificial strawberry flavoring. www.feingold.org/strawberry.html. Accessed April 8, 2019.
6. Quinn ME. Benzyl alcohol. In: Sheskey PJ, Cook WG, Cable CG, eds. Handbook of Pharmaceutical Excipients. 8th ed. London, England: Pharmaceutical Press; 2017:108-110.
7. Rappoport Z, ed. The Chemistry of Phenols. Chichester, England: John Wiley & Sons; 2004.
8. Quinn ME. Ammonium glycyrrhizate. In Sheskey PJ, Cook WG, Cable CG, eds. Handbook of Pharmaceutical Excipients. 8th ed. London, England: Pharmaceutical Press; 2017:73-74.
9. Pirjanian A, Alvarez-Nunez F. Poloxamer. In: Sheskey PJ, Cook WG, Cable CG, eds. Handbook of Pharmaceutical Excipients. 8th ed. London, England: Pharmaceutical Press; 2017:688-693.
10. Driver S. Propylene glycol. In: Sheskey PJ, Cook WG, Cable CG, eds. Handbook of Pharmaceutical Excipients. 8th ed. London, England: Pharmaceutical Press; 2017:795-798.
11. Dubash D, Shah U. Water. In: Sheskey PJ, Cook WG, Cable CG, eds. Handbook of Pharmaceutical Excipients. 8th ed. London, England: Pharmaceutical Press; 2017:1012-1016.
12. Sweetman SC, Ed. Martindale: The Complete Drug Reference. 36th ed. London, England: Pharmaceutical Press; 2009:1770-1771.
13. Quinn ME. Sodium bicarbonate. In Sheskey PJ, Cook WG, Cable CG, eds. Handbook of Pharmaceutical Excipients. 8th ed. London, England: Pharmaceutical Press; 2017:846-850.
14. Amidon GE. Sodium citrate dihydrate. In: Sheskey PJ, Cook WG, Cable CG, eds. Handbook of Pharmaceutical Excipients. 8th ed. London, England: Pharmaceutical Press; 2017:858-860.
15. Hutchins A, Mullarney MP. Sucralose. In Sheskey PJ, Cook WG, Cable CG, eds. Handbook of Pharmaceutical Excipients. 8th ed. London, England: Pharmaceutical Press; 2017:937-937.
16. Shah HC, Singh KK. Xanthan gum. In: Rowe RC, Sheskey PJ, Cook WG, Fenton ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. London, England: Pharmaceutical Press; 2012:897-900.
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