US Pharm. 2012;37(5):43-44.
Method of Preparation: Calculate the quantity of each
ingredient for the amount to be prepared. Accurately weigh or measure
each ingredient. Thoroughly pulverize the required number of tadalafil
tablets to a very fine powder. Add a small quantity of Ora-Plus and mix
to obtain a smooth, uniform suspension. Geometrically, add the remainder
of the Ora-Plus and mix well. Add sufficient Ora-Sweet to volume and
mix well. Package and label.
Use: Tadalafil oral suspension may be used to
treat pulmonary hypertension (PH) in patients who are unable to swallow
the solid oral dosage form.
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 91 days may be used for
this preparation when it is stored at room temperature. In the
supporting stability study, a mean of at least 99% of the initial
concentration of tadalafil remained throughout the 91-day study period
in all suspensions. The stability study found no detectable changes in
color, odor, taste, or pH, and no visible microbial growth was observed.1,2
Quality Control: Quality-control assessment may
include weight/volume, pH, specific gravity, active drug assay, color,
rheologic properties/pourability, physical observation, and physical
stability (discoloration, foreign materials, gas formation, mold
Discussion: PH is hypertension in the
pulmonary circuit. It may be primary or secondary to pulmonary or
cardiac disease (e.g., fibrosis of the lung, mitral stenosis). Pulmonary
circulation is somewhat unique owing to the high blood flow, low
pressure, and low resistance. Since this system can distend the blood
vessels of the lung, it can accommodate large increases in blood flow
with only modest elevations in pressure. However, PH occurs when the
pulmonary artery pressure increases to a level inappropriate for a given
cardiac output. Once PH manifests, it is self-perpetuating and can
introduce secondary structural abnormalities in pulmonary vessels.4
Diagnosis of PH can include dyspnea, fatigue, chest pain, and syncope
upon exertion. A narrow splitting of the second heart sound with a loud
pulmonary component may occur, in addition to right ventricular
hypertrophy and cardiac failure in advanced disease. There may also be
other diagnostic parameters. PH may be idiopathic (formerly primary)
or secondary. Treatment of idiopathic PH includes amlodipine,
diltiazem, nifedipine, oxygen, sildenafil, tadalafil, bosentan,
ambrisentan, epoprostenol, iloprost, beraprost, treprostinil, and
diuretics. Therapy for secondary PH consists primarily of treating the
underlying disorder. Early recognition of PH is crucial, as the
self-perpetuating cycle responsible for rapid clinical progression must
Tadalafil (Cialis, C22H19N3O4,
MW 389.40), a selective phosphodiesterase type 5 inhibitor, is a
vasodilating agent. It occurs as a crystalline solid that is practically
insoluble in water and slightly soluble in ethanol. Commercially,
tadalafil is available as 2.5-, 5-, 10-, and 20-mg almond-shaped,
film-coated tablets. Inactive ingredients include croscarmellose,
sodium, hydroxypropyl cellulose, hypromellose, iron oxide lactose
monohydrate, magnesium stearate, microcrystalline cellulose, sodium
lauryl sulfate, talc, titanium dioxide, and triacetin. The tablets
should be stored at 25°C, with excursions permitted to 15°C to 30°C (USP
controlled room temperature). Tadalafil is approved to treat erectile
dysfunction, but it also is effective in the treatment of PH in adult
and pediatric patients.1,2,5
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.6
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
approximately 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.7
1. U.S. Pharmacopeia 34/National Formulary 29. Rockville, MD: U.S. Pharmacopeial Convention, Inc; 2011:330-373.
2. Pettit RS, Johnson CE, Caruthers RL. Stability of an extemporaneously prepared tadalafil suspension. Am J Health Syst Pharm. 2012; 69:592-594.
3. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
4. McPhee SJ, Papadakis MA, Rabow MW, eds. Current Medical Diagnosis and Treatment. New York, NY: McGraw-Hill Medical; 2011:297-299,408-409.
5. Cialis. In: Physicians’ Desk Reference. 61st ed. Montvale, NJ: Thomson PDR; 2007:1838-1843.
6. Ora-Plus product information. Minneapolis, MN: Paddock Laboratories, Inc; 1992.
7. Ora-Sweet product information. Minneapolis, MN: Paddock Laboratories, Inc; 2004.
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