Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 188, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejps.2023.106512
Keywords
Dissolution; permeation; Biomimetic in vitro methods; PermeaLoop TM; Structured method development; Absorption forecasting; Enabling formulations
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With the increasing demand for candidate-enabling formulations, there is a need for in vitro bioavailability forecasting. This study presents a PermeaLoopTM based dissolution/permeation assay for evaluating drug release and permeation simultaneously using different Itraconazole (ITZ)-based amorphous solid dispersions (ASD) formulations. The standardized approach described in this study contributes to the development of in vitro preclinical drug product development.
Along with the increasing demand for candidate-enabling formulations comes the need for appropriate in vitro bioavailability forecasting. Dissolution/permeation (D/P) systems employing cell-free permeation barriers are increasingly gaining interest, due to their low cost and easy application as passive diffusion bio-predictive profiling in drug product development, as this accounts for nearly 75% of new chemical entities (NCEs) absorption mechanism.To this end, this study comprises theoretical considerations on the design and experimental work towards the establishment and optimization of a PermeaLoopTM based dissolution/permeation assay to simultaneously evaluate the drug release and permeation using Itraconazole (ITZ)-based amorphous solid dispersions (ASD) formulations, with different drug loads, based on a solvent-shift approach. Alternative method conditions were tested such as: donor medium, acceptor medium and permeation barrier were screened using both PermeaPad & REG; and PermeaPlain & REG; 96-well plates. A range of solubilizers, namely Sodium Dodecyl Sulfate, Vitamin E-TPGS and hydroxypropyl-& beta;-cyclodextrin, were screened as possible solubilizing additives to the acceptor medium, while donor medium was varied between blank FaSSIF (phosphate buffer) and FaSSIF. The method optimization also included the ITZ dose selection, being the ITZ single dose (100 mg) considered the most adequate to be used in further experiments to allow the comparison with in vivo studies.In the end, a standardized approach that may be applied to predict the bioavailability of weakly basic poorly soluble drug-based formulations is described, contributing to strengthening the analytical portfolio of in vitro preclinical drug product development.
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