Pharmaceuticals (Nov 2023)

Influence Mechanism of Drug–Polymer Compatibility on Humidity Stability of Crystalline Solid Dispersion

  • Chunhui Hu,
  • Qiuli Yan,
  • Yong Zhang,
  • Haiying Yan

DOI
https://doi.org/10.3390/ph16121640
Journal volume & issue
Vol. 16, no. 12
p. 1640

Abstract

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This study investigates the influence of humidity on the dissolution behavior and microstructure of drugs in crystalline solid dispersions (CSDs). Using Bifonazole (BFZ) as a model drug, CSDs were prepared through spray drying with carriers such as Poloxamer 188 (P188), Poloxamer 407 (P407), and polyethylene glycol 8000 (PEG8000). The solubilization effect and mechanism were initially evaluated, followed by an examination of the impact of humidity (RH10%) on the dissolution behavior of CSDs. Furthermore, the influence of humidity on the microstructure of CSDs was investigated, and factors affecting the humidity stability of CSDs were summarized. Significant enhancements in the intrinsic dissolution rate (IDR) of BFZ in CSDs were observed due to changes in crystalline size and crystallinity, with the CSD-P188 system exhibiting the best performance. Following humidity treatment, the CSD-P407 system demonstrated the least change in the IDR of BFZ, indicating superior stability. The CSD-P407 system was followed by the CSD-P188 system, with the CSD-PEG8000 system exhibiting the least stability. Further analysis of the microstructure revealed that while humidity had negligible effects on the crystalline size and crystallinity of BFZ in CSDs, it had a significant impact on the distribution of BFZ on the CSD surface. This can be attributed to the water’s potent plasticizing effect, which significantly alters the molecular mobility of BFZ. Additionally, the compatibility of the three polymers with BFZ differs, with CSD-P407 > CSD-P188 > CSD-PEG8000. Under the continuous influence of water, stronger compatibility leads to lower molecular mobility and more uniform drug distribution on the CSD surface. Enhancing the compatibility of drugs with polymers can effectively reduce the mobility of BFZ in CSDs, thereby mitigating changes caused by water and ultimately stabilizing the surface composition and dissolution behavior of drugs in CSDs.

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