Pharmaceutical Research

, Volume 24, Issue 5, pp 888–898 | Cite as

Miniaturized Assay for Solubility and Residual Solid Screening (SORESOS) in Early Drug Development

  • Nicole Wyttenbach
  • Jochem Alsenz
  • Olaf Grassmann
Research Paper


The aim was to develop a miniaturized method for solubility and residual solid screening of drug compounds in aqueous and non-aqueous vehicles in early drug development.


Different crystal modifications of caffeine, carbamazepine, and piroxicam were added into 96-well filter plates and solubility was determined in 100 μl of 17 pharmaceutical vehicles. After filtration, drug concentration was determined by Ultra Performance Liquid Chromatography™ (UPLC). Residual solid drug in the filter plates was analyzed by high-throughput (HT) transmission X-ray Powder Diffraction (XRPD).


HT XRPD analysis revealed solid form conversions of all compounds during solubility determination, e.g., formation of hydrates in aqueous vehicles (caffeine, carbamazepine, piroxicam) or conversion of a metastable crystal form to the stable form (caffeine). Drug solubility was strongly dependent on the crystal modifications formed during the solubility assay.


The new assay allows the simultaneous, small scale screening of drug solubility in various pharmaceutical vehicles and identification of changes in solid form. It is useful for the identification of formulations and formulation options in non-clinical and clinical development.

Key words

polymorphism high-throughput solubility ultra performance liquid chromatography (UPLC) X-ray powder diffraction (XRPD) 







differential scanning calorimetry


fasted state simulated intestinal fluid


fed state simulated intestinal fluid


Fourier Transform IR spectroscopy

Mixed micelles (200 mM G/L)

aqueous vehicle containing 200 mM glycocholic acid and 200 mM lecithin


polycarbonate, track-edged




simulated gastric fluid


solubility and residual solid screening


thermo gravimetric analysis


Ultra Performance Liquid Chromatography™


X-ray Powder Diffraction



The authors wish to thank Annunziato Raso for UPLC measurements, Dorothea Held and Sabine Schwarz for standard XRPD analyses, and André Bubendorf for IR spectroscopy studies.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Nicole Wyttenbach
    • 1
  • Jochem Alsenz
    • 1
  • Olaf Grassmann
    • 2
  1. 1.Department of Preclinical ResearchPharma DivisionBasleSwitzerland
  2. 2.Molecular Structure ResearchPharma DivisionBasleSwitzerland

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