Ternary Phase Diagrams of Naproxen with Soluplus® and Chloroform or Ethyl Acetate

This poster has been presented at the 15th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, which took place in Prague, Czech Republic.

Ternary Phase Diagrams of Naproxen with Soluplus® and Chloroform or Ethyl Acetate

Introduction

• Understanding the miscibility behavior of drug-polymer-solvent systems is essential for the design and optimisation of amorphous solid dispersions (ASD).
• Ternary phase diagrams provide valuable insight into the molecular interactions governing solubility, stability, and phase separation [1].
• In this work, ternary phase diagrams were constructed to describe the phase behavior of naproxen, Soluplus®, and selected organic solvents relevant to spray drying/coating of ASDs [2].
• The aim of this study was to construct ternary phase diagrams for naproxen-Soluplus® solvent ternary systems with the combination of theoretical models and experimental results.

Materials

• Naproxen (Biosynth, Slovakia)
• Soluplus® (BASF SE, Germany)
• Ethyl Acetate and Chloroformwere of Pharmacopeia grade and used as received

Methods

• Theoretical Modeling: The ternary Gordon-Taylor equation was applied for the theoretical calculation of the Tg line (glassy region) of the ternary systems (drug, polymer, and solvent) and compare with experimental results.
• Differential Scanning Calorimetry was employed to determine the binary Tg between naproxen and Soluplus®, providing experimental validation for the phase diagram.
• Soluplus® and naproxen were manually milled using a pestle and mortar until a particle size of <50 μm was achieved (verified by optical microscopy).
• Dynamic Vapor Sorption (DVS Advantage, Surface Measurement Systems, UK) measurements were performed on pure naproxen and Soluplus® to obtain binary Tg points on the ternary phase diagram.
• The moisture content of the milled Soluplus® was determined using a Loss on Drying (LOD) method with a (HX204; Mettler Toledo AG, Switzerland) instrument according to standard procedure.
• Phase separation of various naproxen-Soluplus® -solvent mixtures were investigated at 25°C via the film-casting method and subsequent pXRD (Rigaku Co., Japan), and the unstable design space was approximated.

Results

• The apparent solubility of naproxen in Soluplus® was determined to be 68.5 wt.% (Fig. 1).
• The DVS isotherm plot of Soluplus® using chloroform and ethyl acetate show that Soluplus® absorbs chloroform quicker and in a greater quantity than ethyl acetate at 25 ℃ (Fig. 2). The absorption of both solvents by naproxen was negligible at the shown partial pressures.
• The pXRD results of various film-casted naproxen-Soluplus®-solvent mixtures show that the mixtures with a greater quantity of naproxen are more stable with chloroform (Fig. 3) as the solvent. The drying path of these mixtures are presented in the ternary phase diagrams (Fig. 4 and 5) as black dashed lines.
• The ternary phase diagrams show the approximate unstable design space (pXRD-crystallised) at 25 °C (shaded grey area area) (Fig. 4 and 5).

Discussion & Conclusion

• The apparent solubility of naproxen in Soluplus® may be greater than the actual solubility due to kinetic stabilisation (Fig. 1,4 and 5).
• The smaller unstable design space with chloroform (Fig. 5) compared to ethyl acetate (Fig. 4) can be partially explained by the DVS results (Fig. 2) due to the higher affinity of chloroform to Soluplus®, stabilising the system to a greater degree.

See the full poster on Ternary Phase Diagrams of Naproxen with Soluplus®and Chloroform or Ethyl Acetate here

(click the picture to download the poster)

Source: Horváth ZM, Gurkina K, Bērziņš A, Viter R, Mohylyuk V. Ternary phase diagrams of naproxen with Soluplus® and chloroform or ethyl acetate. 15th PBP; Prague, Czech Republic, 2026.03.23-26; DOI: 10.13140/RG.2.2.35480.56320.

Enjoy also the other interesting poster on PBP World Meeting 2026 here: