(694c) Particle Engineering Approaches to Enhance Dissolution Rate & Ensure Redispersibility

With increasing molecular weight and hydrophobicity of small molecule active pharmaceutical ingredients (APIs), achieving a high bioavailability has become more challenging. These Biopharmaceutics Classification System (BCS) class II drugs have high permeability but low solubility in bio-relevant media and require enabling formulations such as amorphous solid dispersions (ASD) to increase their solubility. However, screening for the right polymer and excipients combination for achieving a stable ASD can require extensive efforts. Moreover, these ASDs usually have a low drug load and consequently result in a higher pill burden.

Crystalline formulations with micronized API that can lead to a higher dissolution rate, present a viable alternative since most APIs are isolated as a crystalline solid. Particle size control in the final API crystallization then becomes critical and can be achieved via either a top-down (dry or wet milling of larger crystals) or bottom-up (crystallizing small particles) approach. Irrespective of the approach, very small particles tend to agglomerate during drying, and the agglomerated crystals do not redisperse to their original small size, resulting in a lower dissolution rate.In this work, both top-down and bottom-up approaches were explored for the micronization of a poorly water-soluble API and their dissolution performance was compared. The challenges associated with preserving the nanocrystals obtained from the bottom-up approach were addressed by employing different drying strategies, including the use of excipients to reduce API-API crystal interactions. This work presents a reliable strategy that can be leveraged to obtain nanocrystals that can redispersed to their original size in aqueous media.

Disclosure:

Akshay Korde, Kartik Kamat, Anura Indulkar, Miki Yu, Manish Kelkar, Aaron Featherston, Troy Reynolds and Nandkishor Nere are employees of AbbVie. All authors may own AbbVie stock. AbbVie sponsored and funded the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication.