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Small Molecule

High throughput, low volume solubility measurements

Subvisible Particles Are Important to Small Molecule Drugs

Particle size range chart with accomplanying detection technologies.

Analysis for wide range of particle sizes with BMI.

More Sensitive Kinetic Solubility Measurement

To demonstrate correlation of subvisible particle counts measured on Aura systems to solubility changes, four control compounds with different aqueous solubilities were selected for analysis with BMI. A concentration series for each compound was prepared directly from DMSO stocks, then diluted into PBS, pH 7.4 to 1% DMSO final concentration.

Kinetic solubility range for each compound was reported as the concentration above and below where membrane area coverage by particles exceeded a baseline threshold. The midpoint of this range was assigned as the compound’s estimated solubility.

Ranking of the four test compounds for solubility with the Aura system was identical to ranking by turbidimetry. However, with Aura particle aggregates were detected at 5–10 times lower compound concentration.

The Value of the Unseen

Small scale synthesis of compounds during selection stage can lead to variation of physical form, which can have a dramatic effect on the measured aqueous solubility of compounds. BMI provides high resolution images and digital image analysis of aggregate particles to aid in evaluation of solid-state form.