Calculating the Charcoal Blockade Efficiency for Bioequivalence Study of Inhaled Ipratropium Bromide Using A Model Method

Abstract

Charcoal blockade is a useful approach to block gastrointestinal (GI) absorption of orally inhaled drug products (OIDPs) and therefore can be used effectively to determine drug absorption exclusively via the pulmonary route. Charcoal blockade efficiency (CBE) should be measured to show whether adequate blockade of GI exposure is achieved in bioequivalence (BE) study. The purpose of this study is to employ a model method to calculate the CBE for a pilot pharmacokinetic (PK) BE study of inhaled ipratropium bromide. This model method, based on a convolution integral, is built in-house using MATLAB package. The results demonstrated a full blockade of GI absorption of ipratropium bromide for both test and reference drug products. This study has shown that the model method may provide a useful approach for validation of charcoal blockade method used in PK BE study for OIDPs. The ability to use modeling may simplify human PK studies in general, and is particularly valuable when for ethical, technical or regulatory reasons administration of an orally swallowed form of the drug is not possible.

Keywords: Bioequivalence; Charcoal blockade efficiency; Convolution based pharmacokinetic modelling; In Vitro/In Vivo correlation(s); In silico modelling; Lung drug delivery; Pressurized metered-dose inhaler.