Hot-melt extruded hydroxypropyl methylcellulose acetate succinate based amorphous solid dispersions: Impact of polymeric combinations on supersaturation kinetics and dissolution performance

Nucleation inhibition and maintenance of drug supersaturation over a prolonged period are desirable for improving oral absorption of amorphous solid dispersions. The present study investigates the impact of binary and ternary amorphous solid dispersions on the supersaturation kinetics of nifedipine using the polymers hydroxypropylmethylcellulose acetate succinate (HPMCAS) LG, and HG, Eudragit® RSPO, Eudragit® FS100, Kollidon® VA64 and Plasdone™ K-29/32. The amorphous solubility, nucleation induction time, and particle size analysis of nifedipine in a supersaturated solution were performed with and without the presence of polymers, alone or in combination.

The HPMCAS-HG and HPMCAS-HG + LG combinations showed the highest nifedipine amorphous solubility of 169.47, 149.151 µg/mL, respectively and delay in nucleation induction time up to 120 min compared to other polymeric combinations. The solid dispersions prepared via hot melt extrusion showed the transformation of crystalline nifedipine to amorphous form. The in-vitro non-sink dissolution study revealed that although the binary nifedipine/HPMCAS-LG system had shown the greater supersaturation concentration of 66.1 µg/mL but could not maintain a supersaturation level up to 360 min.

A synergistic effect emerged for ternary nifedipine/HPMCAS-LG/HPMCAS-HG, and nifedipine/HPMCAS-LG/Eudragit®FS100 systems maintained the supersaturation level with enhanced dissolution performance, demonstrating the potential of polymeric combinations for improved amorphous solid dispersion performance.

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Article information: Arun Butreddy, Sandeep Sarabu, Mashan Almutairi, Srinivas Ajjarapu, Praveen Kolimi, Suresh Bandari, Michael A. Repka, Hot-melt extruded hydroxypropyl methylcellulose acetate succinate based amorphous solid dispersions: Impact of polymeric combinations on supersaturation kinetics and dissolution performance, International Journal of Pharmaceutics, Volume 615, 2022. https://doi.org/10.1016/j.ijpharm.2022.121471.


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