US Pharm. 2012;37(2):42-43.
Method of Preparation: Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Obtain the required number of thalidomide capsules (twenty 100-mg capsules). Open the capsules and empty the contents into a mortar. Add the Ora-Plus and blend to form a smooth mixture. Add sufficient Ora-Sweet to final volume and mix well. Package and label.
Note: Alternatively, Ora-Blend may be used as the vehicle to replace the combination of Ora-Plus and Ora-Sweet.
Use: Thalidomide oral suspension is used in the treatment of erythema nodosum leprosum (ENL) and, with dexamethasone, for newly diagnosed multiple myeloma.
Packaging: Package in tight, light-resistant containers.
Labeling: Shake well before taking. Keep out of the reach of children. Discard after ____ [time period].
Stability: A beyond-use date of 35 days may be used for this preparation.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: Thalidomide is a synthetic glutamic acid derivative used as an immunomodulatory agent that has anti-inflammatory, antiangiogenic, and sedative and hypnotic activity. It is indicated for the acute treatment of cutaneous manifestations of moderate-to-severe ENL in leprosy patients and for maintenance therapy for prevention and suppression of cutaneous manifestations of ENL recurrence.4
Thalidomide is teratogenic and has a controlled distribution system. In the 1950s, it was marketed in other countries and was even available OTC in some countries; it was used as a sedative and for the treatment of conditions including asthma, hypertension, migraine, and morning sickness. It was not approved in the U.S. because of reports of serious adverse effects and severe and often fatal fetal and neonatal malformations (usually phocomelia) that affected children in 46 countries. It even affected 17 babies in the U.S. born to mothers who received the drug from overseas sources or through premarketing samples distributed by U.S. pharmaceutical representatives. In 1961, it was withdrawn from the world market. However, it is approved by the FDA with restricted distribution for the indications listed above.4
Thalidomide (Thalomid, C13H10N2O4, MW 258.23) occurs as a white to off-white powder that is highly soluble in dimethylformamide and sparingly soluble in acetone, ethanol, ethyl acetate, glacial acetic acid, and water. It should be preserved in tight containers, protected from light, and stored at controlled room temperature. Thalidomide contains not more than 0.5% water. Thalidomide Capsules USP contain not less than 90.0% and not more than 110.0% of the labeled amount of thalidomide (C13H10N2O4).2
Ora-Plus is an oral suspending vehicle that accepts dilution of up to 50% or more with water, flavoring agents, or syrups and still retains its suspending properties. It has a pH of approximately 4.2 and an osmolality of about 230 mOsm/kg. It is a thixotropic vehicle with a viscosity of approximately 1,000 cps at 25°C. Ora-Plus 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. It is buffered to a pH of approximately 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
Ora-Blend is a sweetened oral suspending vehicle used to simplify the process involved in the extemporaneous compounding of oral suspensions. It is an aqueous-based, sweetened vehicle consisting of a synergistic blend of suspending agents that have a high degree of colloidal activity. Ora-Blend is buffered to a slightly acidic pH of approximately 4.2 and has a viscosity of approximately 700 cps at 25°C and an osmolality of 2,107 mOsm/kg. It occurs as an opaque, pinkish liquid with a sweet citrus-berry flavor. It contains purified water, sucrose, glycerin, sorbitol, flavoring, microcrystalline cellulose, carboxymethylcellulose sodium, xanthan gum, carrageenan, citric acid, and sodium phosphate as buffers and simethicone as an antifoaming agent, and it is preserved with methylparaben and potassium sorbate.7
REFERENCES
1. Kraft S, Johnson CE, Tyler RP. Stability of an extemporaneously prepared thalidomide suspension. Am J Health-Syst Pharm. 2012;69:56-58.
2. U.S. Pharmacopia 34/National Formulary 29. Rockville, MD: U.S. Pharmacopeial Convention, Inc; 2011:330-373,1045,4294-4296.
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. AHFS Drug Information 2011. Bethesda, MD: American Society of Health-System Pharmacists; 2011:3661-3672.
5. Ora-Plus product information. Minneapolis, MN: Paddock Laboratories, Inc; 2010.
6. Ora-Sweet product information. Minneapolis, MN: Paddock Laboratories, Inc; 2010.
7. Ora-Blend product information. Minneapolis, MN: Paddock Laboratories, Inc; 2010.
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