Tadalafil 5 mg/mL Oral Suspension

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 growth).³

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 be interrupted.⁴

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

REFERENCES

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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