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Bioequivalence of Ipratropium Bromide HFA pMDI 20 μg/actuation in Healthy Volunteers with and without Charcoal Blockade and with Spacer Device

Muneesh Garg, Raghu Naidu, Krishnan Iyer, Ratnakar Jadhav and Amol Kumar Birhade

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, 2‑sequence, 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, 2‑sequence, 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, 2‑sequence, 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.