US Pharm. 2016;41(10):24-25.
Method of Preparation: Note—The National Institute for Occupational Safety and Health (NIOSH) classifies bosentan as a hazardous medication; this drug should be handled accordingly.
Calculate the quantity of each ingredient for the amount to be prepared. Accurately obtain each ingredient. Thoroughly pulverize the Tracleer (bosentan monohydrate) tablets (as 10 of the 62.5-mg or five of the 125-mg tablets) to a fine powder. Incorporate sufficient glycerin to form a smooth paste. Add sufficient Flavor Plus:Flavor Sweet (1:1) slowly with thorough mixing to final volume, and mix well. Package and label.
Use: This preparation has been used in the treatment of pulmonary arterial hypertension in patients who cannot swallow the oral solid dosage form.
Packaging: Package in tight, light-resistant containers.1
Labeling: Keep out of reach of children. Use only as directed. Shake well. Discard after ____ [time period].
Stability: A beyond-use date of at least 31 days may be used for this preparation when it is stored either at room temperature or at refrigerated temperatures.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: Bosentan is a new drug used in the treatment of pulmonary arterial hypertension, a progressive illness in which the pulmonary arteries and capillaries in the lungs begin to narrow and become blocked because of the proliferation of cells (including smooth-muscle cells and endothelial cells) in this location. It is indicated to improve exercise ability and to slow clinical worsening.
Bosentan monohydrate (Tracleer, C27H29N5O6S.H2O, MW 569.63) occurs as a white to yellowish powder that is poorly soluble in water (1.0 mg/100 mL) and in aqueous solutions at low pH (0.1 mg/100 mL at pH 1.1 and 4.0; 0.2 mg/100 mL at pH 5.0). The solubility increases at higher pH values (43 mg/100 mL at pH 7.5). In the solid state, bosentan is highly stable, is not hygroscopic, and is not light-sensitive. Tracleer is available in film-coated tablets of 62.5 mg and 125 mg for oral administration. It is available only through a restricted-distribution program called the Tracleer REMS Program. The tablets also contain cornstarch, pregelatinized starch, sodium starch glycolate, povidone, glyceryl behenate, magnesium stearate, hydroxypropyl methylcellulose, triacetin, talc, titanium dioxide, iron oxide yellow, iron oxide red, and ethylcellulose. Each 62.5-mg tablet contains 64.541 mg of bosentan, which is equivalent to 62.5 mg of anhydrous bosentan. Each 125-mg tablet contains 129.082 mg of bosentan, which is equivalent to 125 mg of anhydrous bosentan.4
Glycerin (glycerol, 1,2,3-propane triol) occurs as a clear, colorless, odorless, viscous, hygroscopic liquid with a sweet taste about two-thirds as sweet as that of sucrose. It has a specific gravity of about 1.25 and a melting point of 17.8°C; if cooled to crystallization, it will need to be heated to about 20°C in order to melt. Glycerin is miscible with water, methanol, and 95% ethanol; it is practically insoluble in oils and chloroform and slightly soluble in acetone. Glycerin is hygroscopic and should be stored in airtight containers in a cool place.5
Flavor Plus is a unique flavor-free, aqueous-based suspending vehicle used to simplify the process of compounding oral nonsoluble suspensions. It is buffered to an acidic pH, providing a uniform, consistent, and stable vehicle. Flavor Plus is a white, liquid suspension with a pH of 3.5 to 4.0. Its recommended use is as a vehicle for hydrophilic, acid-stable, and hydrophobic actives, and it is ideal for diabetic preparations.6
Flavor Sweet is a cherry-flavored syrup vehicle formulated to simplify the preparation of oral extemporaneous delivery systems. It may be used alone or in conjunction with other agents to give flavor and sweetness while increasing the suspension’s physical stability. Flavor Sweet contains suitable preservatives and is buffered to a slightly acidic pH to provide a dependable and consistent vehicle. Flavor Sweet occurs as a pink-colored, cherry-flavored syrup with a pH of 4.5 to 5.0. Its recommended use is for hydrophilic, acid-stable, and hydrophobic actives.7
1. U.S. Pharmacopeia/National Formulary [current revision]. Rockville, MD: U.S. Pharmacopeial Convention, Inc; September 2016.
2. Malik A, Gorman G, Coward L, Arnold JJ. Stability of an extemporaneously compounded oral suspension of bosentan. Hosp Pharm. 2016;51:389-395.
3. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
4. Tracleer (bosentan) package insert. South San Francisco, CA: Actelion Pharmaceuticals, Inc; December 2015.
5. Alvarez-Nunez FA, Medina C. Glycerin. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. London, England: Pharmaceutical Press; 2009:283-286.
6. Flavor Plus product information. Austin, TX: Humco; 2016.
7. Flavor Sweet product information. Austin, TX: Humco; 2016.
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