Molecular structure of ketoprofen-polyvinylpyrrolidone solid dispersions prepared by different amorphization methods

Area of Science:

• Materials Science
• Pharmaceutical Science
• Physical Chemistry

Background:

• Amorphous solid dispersions (ASDs) enhance the bioavailability of poorly water-soluble drugs.
• Understanding the influence of processing methods on ASD molecular structure is limited.

Purpose of the Study:

• To investigate how different amorphization techniques affect the molecular structure of ketoprofen/polyvinylpyrrolidone (KTP/PVP) ASDs.
• To compare the molecular mixing and stability of ASDs prepared by various methods.

Main Methods:

• Preparation of KTP/PVP ASDs using five techniques: melt quenching, rotary evaporation, spray drying, and acoustic levitation (premixed and co-sprayed solutions).
• Structural analysis of ASDs using high-energy X-ray total scattering.
• Comparison of X-ray pair distribution functions and structure factors.

Main Results:

• Intramolecular structures were similar across most ASDs of the same composition.
• X-ray structure factors revealed varying degrees of molecular mixing depending on the amorphization route.
• Melt quenching, spray drying, and premixed levitation showed some molecular mixing; co-sprayed levitation resulted in structures similar to physical mixtures.

Conclusions:

• Processing methods demonstrably influence the molecular arrangement and mixing within ASDs.
• X-ray total scattering is effective for benchmarking amorphous forms produced by different techniques.
• The extent of molecular mixing correlates with the stability of ASDs against crystallization.