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Issue: May 2018, Posted Date: 5/1/2018
SOLID FORM SCREENING - Phase Appropriate Strategies for Solid Form Discovery & Development
INTRODUCTION
Solid form screening and selection is an integral part of drug development. Traditionally, it has focused on the search for a crystalline form, such as salts and polymorphs.1-5 In recent years, it has been expanded to include co-crystals and amorphous solid dispersion (ASD) screens for poorly soluble compounds. Solid forms with different properties can be used to overcome various development challenges, such as solubility, stability, or manufacturability.
However, in the early phases of drug development, medicinal chemists and formulators must work together to balance cost, timelines, and quality. The pressure to keep costs down in the early phases, combined with the need to quickly progress development and the high attrition rate of candidates, has led to an increased interest in a phase-appropriate strategy for solid form screening for small molecule candidates.
A phase-appropriate approach is an iterative process, with screening activities becoming more comprehensive as resources become available and technical requirements change. During early development, limited screens are focused on finding a suitable solid form to enable a rapid progression to the next milestone. While later in development, after the clinical proof-of-concept, more material and resources become available, and comprehensive screens may be performed to find all solid forms for intellectual property protection, and identification of the optimal solid form for commercialization.
Poor solubility is a growing issue in drug development, which often leads to unoptimized drugs or increased development timelines.6,7 Utilizing solid form screening to identify a more soluble form, eg, salt or ASD, is a key step for improving the bioavailability and the molecule’s chance of success.1-3,8 For certain molecules, a more soluble solid form can enable preclinical and clinical studies without the use of more advanced enabling formulation technologies.
Throughout the past decade, screening technologies with automated sample preparation and integrated analyses have been developed to support the discovery and evaluation of different solid forms.9,10 These technologies require smaller amounts of material, take less time, and enable the solid form studies to be applied at earlier stages, eg, when comparing pharmacokinetics (PK) of multiple compounds during lead optimization.2 The following describes a rational, fit-for-purpose strategy for solid form screening and selection to...