Miniaturized High-Throughput Amorphous Solid Dispersion Screening via Picoliter Volume 2D-Inkjet Printing of Formulation Microarrays.

Abstract

Many new drug substances exhibit poor physicochemical properties and therefore require significant time and material resources to develop into safe and efficacious medicinal products. This typically involves exploring a large amount of compositional space and may require excessive amounts of drug compounds, which may not be adequate at the early stage of drug development. Scaled-down screening methods have been used as a cost-effective approach to the early-stage formulation. However, even the most material-efficient methods used in product development require milligrams or grams of drug material, which is often not available until relatively late in the lead optimization process. Herein, we report the application of picoliter inkjet printing of drugs and polymers from solution to create addressable formulation microarrays. This allows the efficient screening of drug-polymer compositions while only requiring micrograms or less of the drug substance. A total of eight model compounds, namely, carbamazepine, griseofulvin, saccharin, theophylline, 4-aminobenzoic acid, caffeine, salicylic acid, and benzocaine, were screened against seven commonly used amorphous solid dispersion (ASD) matrix polymers at 5% w/w composition intervals in the range of 5-80% w/w, with five replicates each. Each dispensed spot contains a total of only 1 μg of material (model compound and/or polymer). Across the tested ASD formulations, we ranked the different polymers based on their ability to hinder drug recrystallization across different compositions. Also, we identified distinct physicochemical behaviors in their crystallization kinetics, such as moisture resolubilization. We expect this approach to enable the rapid time- and material-efficient development of new amorphous solid dispersion formulations in an industrial setting.