ADMET & DMPK

Yazarlar: Jernej Štukelj, Mikael Agopov, Jouko Yliruusi, Clare J. Strachan, Sami Svanbäck

Konular:-

DOI:10.5599/admet.839

Anahtar Kelimeler:-

Özet: Poor solubility of crystalline drugs can be overcome by amorphization – the production of high-energy disordered solid with improved solubility. However, the improved solubility comes at a cost of reduced stability; amorphous drugs are prone to recrystallization. Because of recrystallization, the initial solubility enhancement is eventually lost. Therefore, it is important to understand the recrystallization process during storage of amorphous materials and its impact on dissolution/solubility. Here, we demonstrate the use of image-based single-particle analysis (SPA) to consistently monitor the solubility of an amorphous indomethacin sample over time. The results are compared to the XRPD signal of the same sample. For the sample stored at 22 °C/23 % relative humidity (RH), full crystallinity as indicated by XRPD was reached around day 40, whereas a solubility corresponding to that of the γ crystalline form was measured with SPA at day 25. For the sample stored at 22 °C/75 % RH, the XRPD signal indicated a rapid initial phase of crystallization. However, the sample failed to fully crystallize in 80 days. With SPA, solubility slightly above that of the crystalline γ form was measured already on the second day. To conclude, the solubility measured with SPA directly reflects the solid-state changes occurring on the particle surface. Therefore, it can provide vital information – in a straightforward manner while requiring only minuscule sample amounts – for understanding the effect of storage conditions on the dissolution/solubility of amorphous materials, especially important in pharmaceutical science.

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