Purpose: The purpose of this study was to evaluate the in vitro lung dissolution of amorphous and crystalline powder formulations of rifampicin in polyethylene oxide (PEO) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), and to predict the in vivo plasma concentration-time profiles using the in vitro data.
Methods: The in vitro dissolution and permeation profiles of respirable rifampicin particles were studied using a custom-made dissolution apparatus. Data from the in vitro dissolution test were used to estimate the parameters to be used as the input for the simulation of in vivo plasma concentration-time profiles using STELLA® software. For prediction of in vivo profiles, a one-compartment model either with a first order elimination or with a Michaelis-Menten kinetics-based elimination was used.
Results: Compared to the crystalline formulation, the amorphous formulation showed rapid in vitro dissolution suggesting their possible faster in vivo absorption and higher plasma concentrations of rifampicin following lung delivery. However, the simulations suggested that both powder formulations would result in similar plasma-concentration time profiles of rifampicin.
Conclusions: Use of an in vitro dissolution test coupled with a simulation model for prediction of plasma-concentration time profiles of an inhaled drug was demonstrated in this work. These models can also be used in the design of inhaled formulations by controlling their release and dissolution properties to achieve desired lung retention or systemic absorption following delivery to the lungs.
Keywords: amorphous and crystalline; dissolution; dry powder inhalers; rifampicin; simulation.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.