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Analysis of Mechanisms for PVP-Active-Agent Formulation as in Supercritical Antisolvent Spray Process

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Abstract

Supercritical antisolvent technology can precipitate polyvinylpyrrolidone (PVP) particles and crystallize paracetamol (PCM) crystals first separately and then together in the form of a solid dispersion. Supercritical carbon dioxide (scCO2) is used as an antisolvent. For PVP particle generation, ethanol, acetone, and mixtures of ethanol and acetone are used as solvents. The initial concentration of PVP in the solution was varied between 0.5 and 5 wt%, the operation pressure between 10 and 30 MPa, and the composition of ethanol/acetone solvent mixtures between 100 and 0 wt% of ethanol at a constant temperature of 313 K. An increase in the content of the “poor” solvent acetone in the initial solution leads to a significant decrease in mean particle size. Fully amorphous PVP powder always precipitates for all the parameters investigated.

For PCM powder generation, ethanol, acetone, and mixtures of ethanol and acetone are used as solvents. The initial PCM concentration in the solution was varied between 0.5 and 5 wt% and the operation pressure between 10 and 16 MPa. A variation of these parameters leads to a manipulation of the size and the morphology of the crystallized PCM crystals. Irrespective of parameters such as pressure or concentration, the same polymorphic form of paracetamol is always produced for pure solvents. When generating PCM particles from mixtures of ethanol and acetone, two different crystal forms were detected depending on the ratio between the solvents.

The solid dispersions were generated at different ratios of PVP to PCM. These solute mixtures were also dissolved in pure ethanol and pure acetone as well as in different mixtures of these two solvents. Fully amorphous solid dispersions consisting of PCM and PVP together were generated at different ratios of PVP to PCM. All influences of parameters were investigated and discussed in detail.

The mechanisms that control the final particle properties are discussed taking into account two different models for “ideal” and “nonideal” solutes. Furthermore, the study of “unconventional” supercritical antisolvent (SAS) process parameters such as the solvation power of the solvent shows that these parameters qualify to tailor polymer particle properties via SAS processing. In addition, investigating the behavior of both solutes separately, fully amorphous solid dispersions consisting of PCM and PVP together were generated. The crystalline structure and solid dispersions of the particles was analyzed using X-ray and their morphology was analyzed using scanning electron microscopy (SEM).

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Authors and Affiliations

  1. Erlangen Graduate School in Advanced Optical Technologies (SAOT), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany

    Matthias Rossmann, Daniel Bassing & Andreas Braeuer

  2. Lehrstuhl für Prozessmaschinen und Anlagentechnik (iPAT), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany

    Matthias Rossmann, Daniel Bassing & Eberhard Schlücker

  3. Department of Industrial Engineering, University of Salerno, Salerno, Italy

    Iolanda De Marco, Valentina Prosapio & Ernesto Reverchon

  4. Lehrstuhl für Technische Thermodynamik (LTT), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany

    Andreas Braeuer

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  1. Matthias Rossmann
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  3. Iolanda De Marco
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Correspondence to Andreas Braeuer .

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  1. Institute of Materials Science, University of Bremen, Bremen, Germany

    Udo Fritsching

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Rossmann, M. et al. (2016). Analysis of Mechanisms for PVP-Active-Agent Formulation as in Supercritical Antisolvent Spray Process. In: Fritsching, U. (eds) Process-Spray. Springer, Cham. https://doi.org/10.1007/978-3-319-32370-1_24

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