The Effect of the Molecular Weight of Polyvinylpyrrolidone and the Model Drug on Laser-Induced In Situ Amorphization

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 13; p. 4035
• Main Authors: Hempel, Nele-Johanna, Merkl, Padryk, Knopp, Matthias Manne, Berthelsen, Ragna, Teleki, Alexandra, Hansen, Anders Kragh, Sotiriou, Georgios A., Löbmann, Korbinian
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.07.2021; MDPI
• Subjects: Amorphization; amorphous solid dispersion; Celecoxib; Compacts; Dissolution; dissolution kinetics; Drugs; Exposure; Glass; Glass transition temperature; High temperature; in situ amorphization; Indomethacin; Investigations; Kinetics; Laser radiation; Lasers; Medicin och hälsovetenskap; Molecular weight; Naproxen; near-IR laser radiation; plasmonic photothermal nanoparticles; Polymers; Polyvinylpyrrolidone; Radiation; Rapid prototyping; Solubility; Temperature; Transition temperatures; Viscosity
• ISSN: 1420-3049; 1431-5157; 1420-3049
• DOI: 10.3390/molecules26134035

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.