Method of Preparation: Note: This preparation should be compounded in a biological safety cabinet that is suitable for protecting compounding personnel. Any excess materials should be disposed of according to the hazardous-drugs standard operating procedures of the facility.
Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Thoroughly pulverize the thioguanine tablets to a very fine powder. Add the Ora-Plus in portions, and mix to form a smooth paste. Add the Ora-Sweet in portions to a final volume of 100 mL, and mix well. Package and label.
Use: Thioguanine oral suspension has been used in the treatment of both leukemia and inflammatory bowel syndrome.1
Packaging: Package in tight, light-resistant containers.
Labeling: Shake well before taking. Keep out of the reach of children. Discard after 63 days. Store at room temperature.
Stability: A beyond-use date of up to 63 days may be used for this preparation when tablets are used as the source of the drug.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: The literature has described a thioguanine oral suspension prepared using Cologel (methylcellulose) and a combination of simple syrup and cherry syrup.1 Cologel (Eli Lilly) is no longer available; however, a new stability study has been reported on the use of the Ora family of vehicles, as well as a combination of methylcellulose and simple syrup.1 The preparation given here employs Ora-Plus and Ora-Sweet as the vehicle.
Thioguanine (anhydrous, C5H5N5S.xH2O, MW 167.19) occurs as a pale yellow, odorless or practically odorless crystalline powder. Thioguanine is insoluble in water, in alcohol (1 in 7,700), and in chloroform; it is freely soluble in dilute solutions of alkali hydroxides.2 Thioguanine is an analogue of the naturally occurring purine guanine and is an antimetabolite antineoplastic. Its actions and uses are similar to those of mercaptopurine. Thioguanine is administered orally, usually with other antineoplastic agents. Thioguanine is incompletely and variably absorbed from the gastrointestinal tract, and only about 30% is absorbed after oral administration. It should be stored in airtight containers.2-4
Ora-Plus is an oral suspending vehicle that accepts dilution of up to 50% or more with water, flavoring agents, or syrups while still retaining its suspending properties. It has a pH of approximately 4.2 and an osmolality of about 230 mOsm/kg. Ora-Plus is a thixotropic vehicle with a viscosity of approximately 1,000 cps at 25°C. It contains purified water, microcrystalline cellulose, sodium carboxymethylcellulose, xanthan gum, carrageenan, sodium phosphate, and citric acid as buffering agents, simethicone as an antifoaming agent, and potassium sorbate and methylparaben as preservatives.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. It 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. Aliabadi HM, Romanick M, Somayaji V, et al. Stability of compounded thioguanine oral suspensions. Am J Health Syst Pharm. 2011;68:900-908.
2. USP Pharmacists’ Pharmacopeia. 2nd ed. Rockville, MD: US Pharmacopeial Convention, Inc; 2008:775-779,797-831,1464.
3. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
4. Sweetman SC. Martindale: The Complete Drug Reference. London, England: Pharmaceutical Press; 2011:860-861.
5. Ora-Plus product information. Minneapolis, MN: Paddock Laboratories, Inc; 1992.
6. Ora-Sweet product information. Minneapolis, MN: Paddock Laboratories, Inc; 2004.
To comment on this article, contact rdavidson@uspharmacist.com.
