Solubility results vary from batch-to-batch? Or you’ve obtained out-of-specification dissolution test results?

Possible checklist:

  • Polymorphism of your drug substance
  • Variation in particle size distribution from batch-to-batch
  • Quality problem due to particle segregation in manufacturing
  • Water-induced phase transformation in the solubility buffer
  • The crystallisation of the amorphous material
  • Precipitation due to salt disproportionation or co-crystal dissociation
  • Instability of suspension formulation due to particle size growth during storage
  • Formation of rubbery state for amorphous drug/excipient or gelatine capsule
  • The thickness of the coating for control release (CR) or modified release (MR) product

Chauhan H, Kuldipkumar A, Barder T, Medek A, Gu C H, Atef E (2014) Correlation of Inhibitory Effects of Polymers on Indomethacin Precipitation in Solution and Amorphous Solid Crystallization Based on Molecular Interaction, Pharm Res 31(2): 500-515.

Jensen LG, Skautrup FB, Müllertz A, Abrahamsson B, Rades T, Priemel PA (2017) Amorphous is not always better—A dissolution study on solid state forms of carbamazepine. Int J Pharm 522(1-2):74-9.

Konno H, Taylor L S (2006) Influence of Different Polymers on the Crystallisation Tendency of Molecularly Dispersed Amorphous Felodipine. J Pharm Sci 95(12): 2692-2705.

Lehto P, Aaltonen J, Tenho M, Rantanen J, Hirvonen J, Tanninen VP, Peltonen L. (2009) Solvent-Mediated Solid Phase Transformations of cArbamazepine: Effects of Simulated Intestinal Fluid and Fasted State Simulated Intestinal Fluid, J Pharm Sci, 98(3): 985-996..

Shevchenko A, Bimbo LM, Miroshnyk I, Haarala J, Jelínková K, Syrjänen K, van Veen B, Kiesvaara J, Santos HA, Yliruusi J. (2012 ) A new co-crystal and salts of itraconazole: comparison of solid-state properties, stability and dissolution behaviour. Int J Pharm 436(1-2):403-409.

Sovago I, Wang W,  Qiu D, Raijada D, Rantanen J, Grohganz H, Rades T, Bond A D, Löbmann K (2016) Properties of the Sodium Naproxen-Lactose-Tetrahydrate Co-Crystal upon Processing and Storage. Molecules 21(4), 509.

Xia D, Wu J X, Cui F, Qu H, Rades T, Rantanen J, Yang M (2012) Solvent-mediated amorphous-to-crystalline transformation of nitrendipine in amorphous particle suspensions containing polymers. Eur J Pharm Sci 46(5): 446-454

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