Abstract
Ipratropium Bromide is a short-acting (lasting for 6-8 h) anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD). The aim of these three studies was to determine the bioequivalence of test and reference formulations of Ipratropium Bromide HFA pMDI 20 μg/actuation with and without charcoal blockade; and with spacer device. Study-1 was single dose, randomized, 4-period, 2âsequence, laboratory-blinded, crossover, replicate design conducted in 90 healthy volunteers under fasting conditions with concurrent oral charcoal blockade with a washout period of 7-14 days. Study-2 was single dose, randomized, 2-period, 2âsequence, laboratory-blinded, crossover design conducted in 24 healthy volunteers under fasting conditions without concurrent oral charcoal blockade with a washout period of 6 days. Study-3 was single dose, randomized, 2-period, 2âsequence, laboratory-blinded, crossover design conducted in 64 healthy volunteers under fasting conditions with Aero Chamber Plus valved holding chamber with a washout period of 7-10 days. Blood samples were collected up to 24 h postdose for pharmacokinetic profiling. Safety evaluations included monitoring adverse events and vital signs as well as performing clinical laboratory tests. Plasma concentrations of Ipratropium were determined with a validated LCMS/ MS method. The 90% CI of Ipratropium were 91.30-99.91, and 90.42-97.77 for Cmax, and AUC0-t respectively for study-1. The 90% CI of Ipratropium were 87.33-121.30, and 88.94-120.34 for Cmax, and AUC0-t respectively for study-2. The 90% CI of Ipratropium were 87.21-99.83, and 91.66-97.94 for Cmax, and AUC0-t respectively for study-3. Since the 90% CI for Cmax and AUC0-t were within the 80-125% interval, it was concluded that test and reference formulation of Ipratropium Bromide HFA pMDI 20 μg per actuation are bioequivalent in their rate and extent of absorption with and without charcoal blockade; and with spacer device.
Highlights
Chronic obstructive pulmonary disease (COPD) is a lung disease that includes the conditions chronic bronchitis and emphysema
While volunteer was in standing position, a single dose of 4 puffs of the test or the reference product were inhaled by the volunteer as per the randomized sequence in the standing position on four separate treatment days. 50 mL of activated charcoal suspension was given 2 min prior to the 1st puff, immediately after dosing and at 1.00, 2.00 and 4.00 h post-dose as per the method described by Bennett et al [7]
While volunteer was in standing position, a single dose of 4 puffs of the test or the reference product were inhaled by the volunteer as per the randomized sequence in the standing position on two separate treatment days
Summary
Chronic obstructive pulmonary disease (COPD) is a lung disease that includes the conditions chronic bronchitis and emphysema. M2 receptors at cholinergic nerve endings inhibit the release of acetylcholine and act as inhibitory feedback receptors Inhibition of these receptors with ipratropium bromide results in increased acetylcholine release in the airways, which may overcome the blockade of other muscarinic receptors in the muscle [1,2]. The aim of these three studies was to evaluate the rate and extent of absorption of generic formulation of Ipratropium Bromide HFA pMDI 20 μg/actuation against that of innovator formulation (ATROVENT CFC-free (containing ipratropium bromide 20 μg per actuation) marketed by BOEHRINGER INGELHEIM LIMITED, UK), with concurrent oral charcoal blockade, without concurrent oral charcoal blockade and with AeroChamber Plus valved holding chamber under fasting conditions in order to assess bioequivalence. A single dose of Ipratropium Bromide HFA pMDI 40 μg (20 μg/ actuation X 2 puffs) was evaluated in study-3 with AeroChamber Plus valved holding chamber
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