Nano and micro dispersions of two-phase amorphous-amorphous drug formulations as strategy to enhance solubility of pharmaceuticals Academic Article in Scopus uri icon

abstract

  • © 2019 Elsevier Ltd. All rights reserved.Preparation of amorphous solid dispersions (ASD) has been widely used as a strategy to improve the solubility of poorly watersoluble active pharmaceutical ingredients (API). However, immiscibility between a drug and an excipient has been the basis for dismissal of some systems to produce ASDs, because it was believed that phase separation might induce undesired crystallization. In a recent study, we reported that immiscibility between a drug and an excipient matrix can actually be used as an advantage to reduce the particle size of the dispersed drug, thus improving its distribution in the excipient to obtain thermally stable two-phase amorphous-amorphous solid dispersions (AASD) increasing the API's solubility. This preparation focused on a single API; therefore, with the purpose to prove that this novel strategy can be extended to other drugs, in the present work, new amorphous-amorphous simvastatin-glucose (SVS-GLU) solid dispersion were prepared by the melt-quenching technique assisted by ultrasound. This work demonstrates that the application of ultrasound during the preparation of AASD reduces the API's particle size and produces a homogeneous distribution of the drug in the matrix, enhancing SVS's aqueous solubility almost four times, compared with its crystalline form. Furthermore, the amorphous state of the formulation was found to be stable under storage conditions, as evaluated by powder X-ray diffraction. These studies give rise to formulations that can be introduced as novel alternatives to produce thermally stable systems and enhance the solubility of poorly water-soluble drugs.

publication date

  • January 1, 2019