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Related Concept Videos

Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism01:21

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Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
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Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
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Slurry Conversion: A General Method for Formulating Amorphous Solid Dispersions and Fully Integrating Drug and

Amy Lan Neusaenger1, Caroline Fatina1, Yichun Shen1

  • 1University of Wisconsin, School of Pharmacy, Madison, Wisconsin 53705, United States.

Molecular Pharmaceutics
|June 13, 2025
PubMed
Summary

Slurry conversion is a versatile, low-cost, and green method for creating amorphous solid dispersions (ASDs) for poorly soluble drugs. This technique offers a scalable alternative to traditional methods, ensuring drug-polymer integration and improved stability.

Keywords:
X-ray photoelectron spectroscopyamorphous drug–polymer saltsamorphous solid dispersiondegree of salt formationpoly(acrylic acid)slurry conversion

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Area of Science:

  • Materials Science
  • Pharmaceutical Technology
  • Chemical Engineering

Background:

  • Amorphous solid dispersions (ASDs) enhance the solubility and bioavailability of poorly soluble drugs.
  • Conventional ASD manufacturing methods like hot melt extrusion and spray drying have limitations.
  • Slurry conversion offers a solvent-sparing approach to ASD preparation.

Purpose of the Study:

  • To evaluate slurry conversion as a general method for preparing amorphous solid dispersions (ASDs) for 18 poorly soluble drugs.
  • To assess the impact of drug loading and formulation type (binary/ternary) on ASD preparation.
  • To compare slurry conversion with conventional methods regarding efficiency, scalability, and product quality.

Main Methods:

  • Solid mixtures of drugs and poly(acrylic acid) (PAA) were stirred in a minimal amount of ethanol-dichloromethane solvent at room temperature.
  • ASDs were prepared at 25% and 50% drug loadings.
  • Ternary ASDs containing two drugs were also formulated.
  • The process was scaled up by 60-fold to assess industrial applicability.

Main Results:

  • ASDs were successfully prepared for 16 out of 18 drugs at 25% loading and 11 at 50% loading.
  • Complete dissolution and amorphization were indicated by slurry "clearing" for most drugs.
  • Solvent-mediated conversion resulted in fully amorphous products even without clearing.
  • Drug protonation by PAA correlated with drug basicity, indicating thermodynamic equilibrium.
  • Ternary ASDs for combination therapies were successfully prepared.
  • Scale-up to 60-fold showed no adverse effects on product structure or properties.

Conclusions:

  • Slurry conversion is a general, effective, and green method for producing ASDs from a wide range of poorly soluble drugs.
  • The method allows for thermodynamic equilibrium, leading to stable amorphous forms.
  • It is suitable for both binary and ternary formulations, including combination therapies.
  • Slurry conversion is a scalable and cost-effective alternative to conventional ASD manufacturing techniques.