US Pharm. 2015;40(10):61-62.

Method of Preparation: Note—This preparation must be compounded in a biological safety cabinet.

Calculate the quantity of each ingredient for the amount to be prepared. Take all supplies into the anteroom of the biological safety cabinet room and don the appropriate personal protective equipment. Take all supplies into the biological safety cabinet room. Inside the biological safety cabinet, place the pazopanib tablets in a disposable mortar and cover with Sterile Water for Irrigation; allow to set until the tablets begin to disintegrate. Carefully mix with a pestle to form a uniform and smooth paste. Geometrically, add the Ora-Sweet and mix well until the mixture is pourable. Transfer the mixture to an amber glass dispensing bottle and verify the final volume. Swirl (not shake) to mix well. Shaking will increase foaming. Label. Properly dispose of the mortar, pestle, spatulas, personal protective equipment, and any other waste in a hazardous-chemical waste bucket.1

Use: This preparation has been used to treat kidney cancer in adults and solid tumors (sarcoma, neuroblastoma, Wilms’ tumor, osteosarcoma, and brain tumor) in children.1,2

Packaging: Package in an amber glass dispensing bottle.1

Labeling: Keep out of reach of children. Discard after ____ [time period]. Refrigerate. Swirl for 30 seconds prior to removing dose from bottle. DO NOT SHAKE. Cytotoxic.1

Stability: A beyond-use date of 35 days when stored in a refrigerator has been used for this preparation.1,3

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).4

Discussion: Pazopanib hydrochloride (Votrient, C21H23N7O2S.HCl, MW 473.98) is an antineoplastic agent. It occurs as a white to slightly yellow solid. Pazopanib hydrochloride is very slightly soluble at pH 1 and practically insoluble above pH 4 in aqueous media. Votrient tablets are for oral administration; each 200-mg tablet contains 216.7 mg of pazopanib hydrochloride, equivalent to 200 mg of pazopanib free base. The inactive ingredients in the tablet include2

• Tablet core—magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate

• Coating (gray film coating)—hypromellose, iron oxide black, macrogol/polyethylene glycol 400, polysorbate 80, titanium dioxide

Sterile Water for Irrigation is water for injection that has been sterilized and suitably packaged; it contains no antimicrobial agent or other added substance. It is packaged in single-dose glass or plastic containers. The container may contain a volume of more than 1 liter and may be designed to empty rapidly. It is labeled “For irrigation only” and “Not for injection.” Water for injection is water that has been purified by distillation or by reverse osmosis; it contains no added substances. Note that water for injection is not prepared by an ion-exchange process. The term water is used to describe potable water from a public water supply that is suitable for drinking and is the beginning point of the official waters; it is a clear, colorless, odorless, and tasteless liquid. 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).3,5

Ora-Sweet syrup vehicle is a flavoring vehicle for oral extemporaneous preparations. It is flavored with a citrus-berry flavor blend and contains glycerin and sorbitol to prevent cap lock, a problem associated with many syrups. Ora-Sweet is buffered to a pH of about 4.2 and has an osmolality of about 3,240 mOsm/kg. Ora-Sweet contains purified water, sucrose, glycerin, sorbitol (5%), flavoring, sodium phosphate, and citric acid as buffering agents and potassium sorbate and methylparaben as preservatives.6

REFERENCES

1. Source of the formulation: Lisa Ashworth, RPh. Children’s Medical Center Dallas, Dallas, Texas.
2. RxList. Votrient. www.rxlist.com/votrient-drug.htm. Accessed September 2, 2015.
3. U.S. Pharmacopeia 38/National Formulary 33. Rockville, MD: U.S. Pharmacopeial Convention, Inc; 2014:559-611,5807.
4. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
5. Dubash D, Shah U. Water. In: Rowe RC, Sheskey PJ, Cook WG, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:880-884.
6. Ora-Sweet product information. Allegan, MI: Perrigo; 2014.

To comment on this article, contact rdavidson@uspharmacist.com.