Formulating High Drug Load Amorphous Dispersions Through Co-Precipitation

One of the limitations with an amorphous solid dispersion (ASD) formulation strategy is low drug loading. As the drug load in ASD formulations increases, there is often a corresponding decline in release performance. Moreover, low drug load formulations result in larger, harder-to-swallow dosage forms, particularly when high doses are required. In this presentation, we will explore co-precipitation in a high-shear environment as a particle engineering strategy to prepare high drug load ASDs without compromising dissolution performance. While high-shear rotor–stator mixers are widely used in the pharmaceutical industry to reduce particle size and standardize the physical properties of active pharmaceutical ingredients, their application in the manufacturing of drug product intermediates, such as ASDs, remains less explored. We will discuss the innovative use of rotor-stator wet mills for producing high drug load ASDs. The presentation will begin with an overview of the state of the art in co-precipitation technology, focusing specifically on ASD manufacturing, and will highlight the benefits and challenges associated with this approach. Following this, we will present a case study using grazoprevir, a BCS Class IV drug, and hypromellose acetate succinate as the polymer. The case study will include mechanistic studies examining the effects of excipient selection, miscibility, surface composition, and wettability on drug release behavior. Additionally, we will cover key considerations related to processing parameters and scalability. Together, these studies will demonstrate the potential of co-precipitation technology as an advanced solvent-based processing technique to manufacture high drug load ASDs. The presentation will conclude with a discussion of the challenges in ASD manufacturing, particularly for new chemical entities that have increasingly high melting and glass transition temperatures, and how co-precipitation could serve as a next-generation, greener solvent-based technology for ASD manufacturing.