Stability Challenges of Amorphous Solid Dispersions of Drugs: A Critical Review on Mechanistic Aspects

Abstract

The most common drawback of the existing and novel drug molecules is their low bioavailability because of their low solubility. One of the most important approaches to enhance the bioavailability in the enteral route for poorly hydrophilic molecules is amorphous solid dispersion (ASD). The solubility of compounds in amorphous form is comparatively high because of the availability of free energy produced during formulation. This free energy results in the change of crystalline nature of the prepared ASD to the stable crystalline form leading to the reduced solubility of the product. Due to the intrinsic chemical and physical uncertainty and the restricted knowledge about the interactions of active molecules with the carriers making, this ASD is a challenging task. This review focused on strategies to stabilize ASD by considering the various theories explaining the free-energy concept, physical interactions, and thermal properties. This review also highlighted molecular modeling and machine learning computational advancement to stabilize ASD.

Investigation of the Influence of Anti-Solvent Precipitation Parameters on the Physical Stability of Amorphous Solids

“…Therefore, the experimental findings suggested that elevating the agitation speed to 500 rpm resulted in the formation of a more physically stable amorphous solid in the present investigation. 2 represents the goodness of fit, while the Q 2 represents the goodness of prediction). The crystalline Form A was used as a reference sample; the feeding rate was fixed at 5 mL/min, and the aging time was fixed at 10 min.…”

“…These thermal effects can significantly impact the physical stability of amorphous solids. Consequently, the DSC analysis 2 represents the goodness of fit, while the Q 2 represents the goodness of prediction). The crystalline Form A was used as a reference sample; the feeding rate was fixed at 5 mL/min, and the aging time was fixed at 10 min.…”

“…This transition involves the reduction of amorphous solids' molecule mobility and the enhancement of intermolecular interactions, potentially leading to improved physical stability [46]. Additionally, aging time facilitates the struc- 2 represents the goodness of fit, while the Q 2 represents the goodness of prediction). The crystalline Form A was used as a reference sample; the feeding rate was fixed at 5 mL/min, and the agitation speed was fixed at 500 rpm.…”

“…Recently, there has been significant attention given to amorphous solids due to their enhanced solubility and dissolution rates in comparison with their low aqueous solubility crystalline form [ 1 , 2 ]. However, amorphous solids are unstable and can transform into a crystalline form, reducing the solubility and bioavailability of active pharmaceutical ingredients (APIs) [ 3 , 4 ].…”

“…Figure 7. The influence of aging time on the formation of nilotinib free base amorphous solids: (a) PXRD patterns; (b) PDF trace (the NNN represents the next nearest neighbor atoms in the nilotinib free base solid samples); (c) G NNN value; (d) PCA scores plot (the R2 represents the goodness of fit, while the Q 2 represents the goodness of prediction). The crystalline Form A was used as a reference sample; the feeding rate was fixed at 5 mL/min, and the agitation speed was fixed at 500 rpm.…”