Related Experiment Video
Updated: Aug 5, 2026

Flash NanoPrecipitation for the Encapsulation of Hydrophobic and Hydrophilic Compounds in Polymeric Nanoparticles
Published on: January 7, 2019
Impact of mixing method on amorphous solid dispersions fabricated via vacuum compression molding: dissolution and
Shuaiqian Men1, James E Polli1
1Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
Abstract:
Amorphous solid dispersions (ASD) melting-based methods such as hot-melt extrusion (HME) provide effective mixing during processing, whereas vacuum compression molding (VCM) lacks intrinsic mixing. Cryo-milling (CM) is commonly employed prior to VCM to enhance powder mixing; however, it remains unclear what particle size characteristics are required to ensure sufficiently homogeneous, single-phase ASDs. This study evaluated the impact of mixing methods on dissolution performance of ritonavir (RTV)/poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) ASD discs fabricated by VCM, comparing physical blending (PB) and CM. Solid-state properties were characterized. Discs with 5-50% drug loadings (DLs) were analyzed by microscope-enabled disc dissolution system (MeDDiS). Although attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) and pigment tests indicated similar bulk mixing uniformity, dissolution behavior of PB and CM discs differed significantly. CM discs showed a distinct "cliff" near 30% DL, while PB discs were generally inferior, showing progressively reduced release. ATR- FTIR further revealed that PB led to localized amorphous drug-rich domains, whereas CM promoted more uniform dispersion. Collectively, these findings highlight that effective ASD performance was governed not only by powder mixing, but also by the extent of microstructural fusion achieved during molding as a result of improved spatial proximity between drug and polymer within pre-VCM powder.
Related Concept Videos
Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
In Vitro Drug Dissolution: Alternative Methods
In Vitro Drug Dissolution: Compendial Testing Models I
Factors Affecting Dissolution: Particle Size and Effective Surface Area
In Vitro Drug Dissolution: Compendial Testing Models II
Polymer Classification: Crystallinity
Crystalline domains are the regions where polymer chains are aligned in an orderly manner and held together in proximity by intermolecular forces. For example, chains in the crystalline domains of polyethylene and nylon are bound together by van der Waals...
