Evaluation of drug-polymer miscibility in amorphous solid dispersion systems

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Amorphous solid dispersions (ASDs) are crucial for improving the solubility and bioavailability of poorly soluble drugs.
• Understanding drug-polymer miscibility is key to designing stable and effective ASDs.
• Various analytical techniques are employed to characterize the interactions within ASDs.

Purpose of the Study:

• To investigate the drug-polymer miscibility behavior in four distinct amorphous solid dispersion systems.
• Systems studied include felodipine-poly(vinyl pyrrolidone) (PVP), nifedipine-PVP, ketoconazole-PVP, and felodipine-poly(acrylic acid) (PAA).

Main Methods:

• Amorphous solid dispersion samples were prepared at varying drug-to-polymer ratios.
• Analysis involved differential scanning calorimetry (DSC), mid-infrared (IR) spectroscopy, and powder X-ray diffractometry (PXRD).
• Principal components analysis (PCA) aided IR spectra interpretation, while Pair Distribution Functions (PDFs) and Pure Curve Resolution Method (PCRM) were used with PXRD data.

Main Results:

• Complete molecular-level mixing was confirmed for nifedipine-PVP and felodipine-PVP systems.
• Felodipine-PAA exhibited drug-polymer immiscibility at 30-70% polymer, with partial mixing indicated at 10% and 90% polymer concentrations.
• Ketoconazole-PVP showed suspected partial miscibility, with unambiguous one-phase ASD confirmed only at higher polymer concentrations.

Conclusions:

• Differential scanning calorimetry, IR spectroscopy, and PXRD collectively enhance the assessment of drug-polymer miscibility in ASDs.
• IR spectroscopy and PXRD are particularly valuable for detecting local chemical and structural changes, aiding miscibility elucidation.
• These techniques provide complementary insights, especially when DSC results are ambiguous or variable.