The effect of the molecular weight of polyvinylpyrrolidone and the model drug on laser-induced in situ amorphization

Nele Johanna Hempel, Padryk Merkl, Matthias Manne Knopp, Ragna Berthelsen, Alexandra Teleki, Anders Kragh Hansen, Georgios A. Sotiriou, Korbinian Löbmann*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Laser radiation has been shown to be a promising approach for in situ amorphization, i.e., drug amorphization inside the final dosage form. Upon exposure to laser radiation, elevated temperatures in the compacts are obtained. At temperatures above the glass transition temperature (Tg) of the polymer, the drug dissolves into the mobile polymer. Hence, the dissolution kinetics are dependent on the viscosity of the polymer, indirectly determined by the molecular weight (Mw) of the polymer, the solubility of the drug in the polymer, the particle size of the drug and the molecular size of the drug. Using compacts containing 30 wt% of the drug celecoxib (CCX), 69.25 wt% of three different Mw of polyvinylpyrrolidone (PVP: PVP12, PVP17 or PVP25), 0.25 wt% plasmonic nanoaggregates (PNs) and 0.5 wt% lubricant, the effect of the polymer Mw on the dissolution kinetics upon exposure to laser radiation was investigated. Furthermore, the effect of the model drug on the dissolution kinetics was investigated using compacts containing 30 wt% of three different drugs (CCX, indomethacin (IND) and naproxen (NAP)), 69.25 wt% PVP12, 0.25 wt% PN and 0.5 wt% lubricant. In perfect correlation to the Noyes–Whitney equation, this study showed that the use of PVP with the lowest viscosity, i.e., the lowest Mw (here PVP12), led to the fastest rate of amorphization compared to PVP17 and PVP25. Furthermore, NAP showed the fastest rate of amorphization, followed by IND and CCX in PVP12 due to its high solubility and small molecular size.

Original languageEnglish
Article number4035
Issue number13
Number of pages13
Publication statusPublished - 1 Jul 2021

Bibliographical note

Funding Information:
Funding: All authors gratefully acknowledge funding from NordForsk (Nordic University Hub project No. 85352; Nordic POP). The authors N.H., M.M.K., R.B. and K.L., would like to thank the Independent Research Fund Denmark for financial support (Grant No. DFF-7026-00052B). G.A.S. acknowledges funding received from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (ERC Grant agreement No. 758705), the Swedish Foundation for Strategic Research (FFL18-0043) and from the Swedish Research Council (2016-03471). The Science for Life Laboratory is gratefully acknowledged for financial support by A.T.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Amorphous solid dispersion
  • Dissolution kinetics
  • In situ amorphization
  • Near-IR laser radiation
  • Plasmonic photothermal nanoparticles


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