The potential of amorphous solid dispersions to improve the solubility, dissolution rate and bioavailability of poorly water soluble drugs is well known. However, the number of formulations that have made it through to the market is limited because of the unstable nature of the amorphous form, which often results in recrystallization of the drug with the subsequent loss of the solubility and dissolution advantages. Thus, ensuring the stability constitutes a major challenge in the development of amorphous solid dispersions.
Lipid-based drug delivery systems have become a popular approach for the delivery of poorly water-soluble drugs. The limitations associated with this formulation strategy have been the drug solubility in the delivery systems and the lack of characterization techniques predicting the in vivo performance. Solid state characterization of the in vitro digestion products has provided new insights that scrutinize current paradigms in the development of lipid-based drug delivery systems.
Formulation of co-amorphous drug systems
Using the amorphous form of a drug, instead of its crystalline counterpart is one way to enhance the bioavailability of poorly water-soluble drugs. However, in order to fully benefit from the solubility advantages of amorphous drugs, one needs to overcome phyisco-chemical limitations including poor physical stability associated with the amorphous form. Co-amorphous drug formulations are a novel and one of the most promising formulation approaches in this context, where the drug in its amorphous form is stabilized through strong intermolecular interactions with its co-amorphous low molecular weight partner molecule.
The major challenge during preformulation is to gain the greatest possible knowledge about candidate drug compounds with minimal use of resources. Therefore, rapid approaches are proposed for identifying critical conditions for existence of various solid forms so that sudden appearance of new forms and unpredictable stability issues can be avoided during later stages of product development.