Effect of supercritical CO₂plasticization on the degradation and residual crystallinity of melt-extruded spironolactone

Abstract

Immediate-release solid dispersions of a slowly dissolving active pharmaceutical ingredient, spironolactone, were prepared by supercritical-CO 2 -assisted melt extrusion (a solvent-free and continuous manufacturing technology) using Eudragit E as matrix. Through optimizing process parameters (i.e. temperature, melt throughput, pressure and CO 2 flow), stable foams with high porosity, homogeneous structure and thin (even submicronic) walls could be prepared, as revealed by scanning electron microscopy. The samples were found to be rigid enough to mill, enabling further processing, as is necessary to formulate tablets. The influence of extrusion temperature and melt throughput on residual drug crystallinity was measured using non-invasive confocal Raman mapping coupled with chemometric analysis, while the influence on the degree of drug degradation was determined using high performance liquid chromatography. The plasticizing effect of supercritical CO 2 was shown to reasonably improve the purity of the prepared solid dispersions by enabling high-yield production at lower temperature ranges. At the same time, shorter residence time and lower temperature slightly increased residual drug crystallinity. The obtained foamy structures ensured immediate drug dissolution in an acidic medium.

Extrusion assisted by supercritical CO 2 : A review on its application to biopolymers

“…1. Schematic of the single-screw extruder used by Fages et al [15,[19][20][21][22][23]. (Reprinted with permission from [15], © 2014 Elsevier).…”

Application of Vibrational Spectroscopy to Study Solid-state Transformations of Pharmaceuticals

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Elucidation and visualization of solid-state transformation and mixing in a pharmaceutical mini hot melt extrusion process using in-line Raman spectroscopy

“…This throughput can be reduced somewhat by using supercritical CO2 as a diluent (Verreck et al, 2006;Vigh et al, 2014b). A mini extruder consists of co-rotating conical twin-screws and an internal recirculation channel to achieve (complete) mixing of the raw materials (drug substance + matrix).…”