SPIRIVA HandiHaler consists of a capsule dosage form containing a dry powder formulation
of tiotropium intended for oral inhalation only with the HandiHaler device.
Each light green, hard gelatin SPIRIVA capsule contains 18 mcg tiotropium (equivalent to
22.5 mcg tiotropium bromide monohydrate) blended with lactose monohydrate (which may contain
milk proteins) as the carrier.
The dry powder formulation within the SPIRIVA capsule is intended for oral inhalation only.
The active component of SPIRIVA HandiHaler is tiotropium. The drug substance, tiotropium bromide
monohydrate, is an anticholinergic with specificity for muscarinic receptors. It is chemically
described as (1α, 2ß, 4ß, 5α, 7ß)-7-[(Hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane
bromide monohydrate. It is a synthetic, non-chiral, quaternary ammonium compound. Tiotropium
bromide is a white or yellowish white powder. It is sparingly soluble in water and soluble in
methanol.
The structural formula is:
Tiotropium bromide (monohydrate) has a molecular mass of 490.4 and a molecular formula
of C19H22NO4S2Br • H2O.
The HandiHaler device is an inhalation device used to inhale the dry powder contained in the SPIRIVA capsule.
The dry powder is delivered from the HandiHaler device at flow rates as low as 20 L/min. Under standardized in
vitro testing, the HandiHaler device delivers a mean of 10.4 mcg tiotropium when tested at a flow rate of
39 L/min for 3.1 seconds (2 L total). In a study of 26 adult patients with COPD and severely compromised lung
function [mean FEV1 1.02 L (range 0.45 to 2.24 L); 37.6% of predicted (range 16% to 65%)], the median peak
inspiratory flow (PIF) through the HandiHaler device was 30.0 L/min (range 20.4 to 45.6 L/min). The amount
of drug delivered to the lungs will vary depending on patient factors such as inspiratory flow and peak
inspiratory flow through the HandiHaler device, which may vary from patient to patient, and may vary with
the exposure time of the SPIRIVA capsule outside the blister pack.