(68b) Particle Engineering at the Drug Substance, Drug Product Interface – Inherently Continuous Processes Yielding Advantageous Material Properties

Results will be presented on a three tiered approach to achieve advanced drug product intermediates addressing the inherently challenging properties of poorly soluble API’s. These include:

1) the incorporation of excipients during particle formation and subsequent isolation and drying of drug substance processing, which has historically been a vastly underrepresented area of development in the pharmaceutical industry

2) the use of a novel, high shear mixing device to allow a revised approach to precipitation to achieve either nano crystalline materials or amorphous solid dispersions

3) subsequent particle isolation utilizing a thin film evaporator, which yields additional capability to modify individual particle (i.e. surface characteristics and local dissolution rates) and bulk level (powder flow and compressbility) properties through selection of process parameters and/or further incorporation of excipients.

Ultimately this allows for the design of complex materials using a continuous, volumetrically productive process. Additionally, the drug product intermediates afford streamlined drug product processing, including continuous direct compression. Work will be presented for multiple component systems achieving high drug load intermediates comprised of 1) co-precipitated amorphous solid dispersions (cPAD) and 2) nano crystalline API.