A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development.

Several literature publications have described the potential application of active pharmaceutical ingredient (API)-polymer phase diagrams to identify appropriate temperature ranges for processing amorphous solid dispersion (ASD) formulations via the hot-melt extrusion (HME) technique. However, systematic investigations and reliable applications of the phase diagram as a risk assessment tool for HME are non-existent. Accordingly, within AbbVie, an HME risk classification system (HCS) based on API-polymer phase diagrams has been developed as a material-sparing tool for the early risk assessment of especially high melting temperature APIs, which are typically considered unsuitable for HME.

Crystallization Risk Assessment of Amorphous Solid Dispersions by Physical Shelf-Life Modeling: A Practical Approach.

Amorphous solid dispersions (ASDs) of a poorly water-soluble active pharmaceutical ingredient (API) in a polymer matrix can enhance the water solubility and therefore generally improve the bioavailability of the API. Although examples of long-term stability are emerging in the literature, many ASD products are kinetically stabilized, and inhibition of crystallization of a drug substance within and beyond shelf life is still a matter of debate, since, in some cases, the formation of crystals may impact bioavailability. In this study, a risk assessment of API crystallization in packaged ASD drug products and a mitigation strategy are outlined.

Assessment of the amorphous solid dispersion erosion behavior following a novel small-scale predictive approach.

In general, the erosion rate of copovidone-based amorphous solid dispersions (ASDs) in contact with water diminishes with increasing drug load, causing poor drug release from the final drug product. A new easy-to-use tool with low material- and time-consumption, the microscopic erosion time test (METT), was established to allow prediction of the API-specific drug load threshold between an eroding and a non-eroding ASD. This API-specific drug load value is further described as the drug load dispersibility limit (DDL) and is the highest drug load at which an eroding ASD was still observed.

Optically pure, monodisperse cis-oligodiacetylenes: aggregation- induced chirality enhancement.

Conformational changes in the conjugated backbone of poly- and oligodiacetylenes (PDAs and ODAs) play an important role in determining the electronic properties of these compounds. At the same time, conformational changes can also result in a folded structure that shows helical chirality. Using d-camphor as a chiral building block, we have designed a high-yielding, iterative synthesis of monodisperse, optically pure cis-oligodiacetylenes (ODAs).