Related Experiment Video
Updated: Dec 27, 2025

A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
Amorphous solid dispersions containing residual crystallinity: Influence of seed properties and polymer adsorption on
Dana E Moseson1, Andrew S Parker2, Stephen P Beaudoin2
1Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN 47907, United States.
Abstract:
The solubility advantage of amorphous solid dispersions (ASDs) is contingent upon supersaturation being generated and maintained. If crystals are present within an ASD, these crystals directly result in lost solubility advantage, and may also seed crystal growth leading to desupersaturation. The goal of this study was to evaluate the impact of residual crystals on ASD supersaturation profiles. Indomethacin-copovidone (PVPVA) ASDs with different levels of residual crystallinity were manufactured by hot melt extrusion (HME). PVPVA at 5 and 50 µg/mL was found to be a highly effective nucleation and crystal growth inhibitor of indomethacin at high supersaturation. Evidence of polymer adsorption onto indomethacin crystals was observed by atomic force microscopy and scanning electron microscopy. HME ASDs containing 0-25% residual crystallinity demonstrated lost solubility advantage, along with minimal desupersaturation during non-sink dissolution testing. While bulk seeds did not properly represent the impact of residual crystals, extensive polymer adsorption onto residual seed crystals resulted in poisoned crystal growth, limiting the potential dissolution performance consequences. Several risk factors related to the presence of residual crystallinity were identified: polymeric crystal growth inhibition effectiveness, seed properties, and supersaturation conditions.
More Related Videos
11:42Synthesis of Monodisperse Cylindrical Nanoparticles via Crystallization-driven Self-assembly of Biodegradable Block Copolymers
Published on: June 20, 2019
05:08Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
Published on: September 20, 2017
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...
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...
Factors Influencing Drug Absorption: Pharmaceutical Parameters
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
Factors Affecting Dissolution: Particle Size and Effective Surface Area
Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence