Spatial characterization of hot melt extruded dispersion systems using thermal atomic force microscopy methods: the...

Area of Science:

• Pharmaceutical Science
• Materials Science
• Analytical Chemistry

Background:

• Hot melt extrusion (HME) is a key technique for creating amorphous solid dispersions.
• Understanding phase separation in drug delivery systems is crucial for efficacy.
• Cyclosporine A in Eudragit EPO presents challenges in achieving stable, single-phase formulations.

Purpose of the Study:

• To evaluate nano-scale localized thermal analysis (LTA) and transition temperature microscopy (TTM) as a combined approach.
• To investigate phase separation in cyclosporine A (CsA) dispersions prepared by HME and spin coating.
• To compare these novel nanothermal techniques with conventional methods like MTDSC and FTIR.

Main Methods:

• Preparation of dispersions using HME (110°C and 150°C, 5 and 15 min) and spin coating.
• Analysis using modulated temperature differential scanning calorimetry (MTDSC) and FTIR spectroscopy.
• Application of nano-scale localized thermal analysis (nano-LTA) and transition temperature microscopy (TTM).

Main Results:

• Spin-coated samples indicated molecular dispersion.
• HME samples at 110°C showed inhomogeneity via MTDSC/FTIR; samples at 150°C appeared homogeneous by MTDSC.
• Nanothermal methods detected phase-separated CsA even at higher HME temperatures, with TTM mapping compositional variations.

Conclusions:

• Transition temperature microscopy (TTM) is a valuable new method for detecting phase separation.
• Phase separation in HME dispersions can be missed or underestimated by conventional bulk analytical techniques.
• Nano-LTA and TTM provide critical insights into the micro-heterogeneity of solid dispersions.