Surface Characterization as a Tool for Identifying the Factors Affecting the Dissolution Rate of Amorphous Solid...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Amorphous solid dispersions (ASDs) are crucial for improving the dissolution of poorly soluble drugs.
• Selecting optimal polymers and drug loadings for ASDs can be challenging and time-consuming.
• Surface properties, including composition and wetting, critically influence ASD tablet dissolution rates.

Purpose of the Study:

• To investigate the relationship between surface characteristics and the dissolution rate of ASD tablets.
• To identify key surface properties that govern the dissolution behavior of itraconazole-HPMCAS ASDs.
• To establish surface characterization as a tool for early-stage formulation screening of ASDs.

Main Methods:

• Preparation of ASDs using spray drying with itraconazole and three grades of hypromellose acetate succinate (HPMCAS) at various drug loadings (10-50%).
• Fabrication of ASD tablets with two different porosities.
• Surface characterization via contact angle measurements (Drop Shape Analyzer) to determine surface free energy, disperse, and polar fractions.
• Analysis of ASD tablets using Near-Infrared (NIR) spectroscopy and dissolution testing.
• Chemometric analysis including Principal Component Analysis (PCA) and Partial Least Squares (PLS) modeling.

Main Results:

• Contact angles, surface free energy, and polar fraction were identified as significant factors influencing the dissolution rate of ASD tablets.
• PLS modeling correlated NIR spectral data and wetting properties with dissolution rates.
• The study elucidated the interplay between surface properties and drug dissolution from ASD tablets.

Conclusions:

• Surface characterization techniques provide valuable insights into the dissolution behavior of ASD tablets.
• Wetting properties (contact angles, surface free energy, polar fraction) are critical determinants of dissolution rate.
• Surface characterization can serve as an effective tool for screening and optimizing ASD formulations and compaction processes during early drug development.