Tadalafil 5 mg/mL Oral Suspension

Loyd V. Allen, Jr., PhD

Professor Emeritus
College of Pharmacy, University of Oklahoma
Oklahoma City, Oklahoma


5/22/2012
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 growth).
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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, C
22
H
19
N
3
O
4
, 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 25C, with excursions
permitted to 15C to 30C (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 25C. 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