Microstructure of an Immiscible Polymer Blend and Its Stabilization Effect on Amorphous Solid Dispersions

• Published in: Molecular pharmaceutics Vol. 10; no. 7; pp. 2767 - 2780
• Main Authors: Yang, Ziyi, Nollenberger, Kathrin, Albers, Jessica, Craig, Duncan, Qi, Sheng
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.07.2013
• Subjects: Crystallization; Hydrophobic and Hydrophilic Interactions; Polymers - chemistry; Spectroscopy, Fourier Transform Infrared; polymer; crystallization; phase separation; amorphous; surface
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/mp400209w

This study proposes use of the phase separation of immiscible polymer blends as a formulation approach to improve the stabilization and solubilization of amorphous molecular dispersions of poorly soluble drugs. This approach uses the phase separation and different drug solubilization properties of the two immiscible polymers in the blend to optimize drug loading and stabilization. The model system tested in this study is a EUDRAGIT E PO-PVP-VA 50/50 (w/w) blend loaded with felodipine via hot melt extrusion. The phase separation behavior of the polymer blend and drug loaded polymer blend formulations were characterized using a range of thermal (MTDSC), spectroscopic (ATR-FTIR), and imaging (AFM and thermal transition mapping) techniques. The polymer blend formulations demonstrated superior performance in drug release as well as stabilization against stressed temperature, stressed humidity, and mechanical milling in comparison to the drug–polymer binary systems. This is attributed to the configuration of the phase separated microstructure of the polymer blend formulations where the hydrophilic polymer domains host high concentrations of molecularly dispersed drug which are protected from moisture induced recrystallization on aging by the hydrophobic polymer domains. Additionally drug incorporation as a molecular dispersion in different polymer phases reduces the drug recrystallization tendency on aging under high temperatures and during milling.