Effect of supercritical CO2 plasticization on the degradation and residual crystallinity of melt-extruded spironolactone

Tamás Vigh, Martial Sauceau, Jacques Fages, Elisabeth Rodier, István Wagner, Péter L. Sóti, G. Marosi, Zsombor K. Nagy

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Immediate-release solid dispersions of a slowly dissolving active pharmaceutical ingredient, spironolactone, were prepared by supercritical-CO2-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 CO2 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 CO2 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.

Original languageEnglish
Pages (from-to)1135-1144
Number of pages10
JournalPolymers for Advanced Technologies
Volume25
Issue number10
DOIs
Publication statusPublished - Oct 1 2014

Fingerprint

Spironolactone
Degradation
Dispersions
Pharmaceutical Preparations
Extrusion
Throughput
Temperature
High performance liquid chromatography
Drug products
Foams
Dissolution
Porosity
Tablets
Scanning electron microscopy
Processing

Keywords

  • Amorphization
  • Degradation
  • Foaming
  • Immediate release
  • Supercritical-fluid extrusion

ASJC Scopus subject areas

  • Polymers and Plastics

Cite this

Effect of supercritical CO2 plasticization on the degradation and residual crystallinity of melt-extruded spironolactone. / Vigh, Tamás; Sauceau, Martial; Fages, Jacques; Rodier, Elisabeth; Wagner, István; Sóti, Péter L.; Marosi, G.; Nagy, Zsombor K.

In: Polymers for Advanced Technologies, Vol. 25, No. 10, 01.10.2014, p. 1135-1144.

Research output: Contribution to journalArticle

Vigh, Tamás ; Sauceau, Martial ; Fages, Jacques ; Rodier, Elisabeth ; Wagner, István ; Sóti, Péter L. ; Marosi, G. ; Nagy, Zsombor K. / Effect of supercritical CO2 plasticization on the degradation and residual crystallinity of melt-extruded spironolactone. In: Polymers for Advanced Technologies. 2014 ; Vol. 25, No. 10. pp. 1135-1144.
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