Effect of Polymer Molecular Weight on the Crystallization Behavior of Indomethacin Amorphous Solid Dispersions

Abstract

The influence of the molecular weight of polyvinylpyrrolidone (PVP) on the molecular mobility and physical stability of indomethacin (IMC)–PVP solid dispersions was investigated over a wide temperature range in the supercooled state. As the polymer molecular weight increased, there was a decrease in molecular mobility as evident from the longer α-relaxation times. Inhibition of IMC crystallization also increased as a function of polymer molecular weight. The extent of H-bonding interaction between drug and polymer, quantified by ssNMR, was independent of polymer molecular weight. Over a polymer concentration range of 5–20% w/w, the temperature dependence of mobility and viscosity was reasonably similar for different grades of PVP. It was concluded that the increase in effectiveness in crystallization inhibition as a function of polymer molecular weight is due to the increased viscosity, which slows down the mobility of these systems.

Influence of the Polymer Glass Transition Temperature and Molecular Weight on Drug Amorphization Kinetics Using Ball Milling

“…In this regard, it is important to emphasize that it has been shown that the polymer M w does not influence the equilibrium solubility of the drug in the polymer at ambient temperature [14]. On the other hand, it has been shown that an ASD comprising the drug IND together with PVP of a higher M w (K30) showed increased physical stability as a result of overall reduced molecular mobility compared to an ASD with PVP of lower M w (K12) [8]. In other words, whilst a higher M w is more efficient at preventing crystallization, it also requires longer milling times to achieve a fully amorphous solid dispersion.…”

“…In this regard, it has been shown that increasing the polymer chain length/molecular weight (M w ) increases the physical stability of an ASD of indomethacin (IND) in polyvinylpyrrolidone (PVP) as a result of overall reduced molecular mobility [8]. Furthermore, the M w of the polymer has also been shown to affect the dissolution rate and performance of the drug from an ASD.…”

Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions

“…Additionally, polymers with a high T g may cause difficulties in processing. For instance, the use of such high T g polymers in hot melt extrusion (HME), one of the most popular preparation methods for ASDs, usually requires the aid of plasticizers, which in turn will reduce the systemic T g [30,31]. Polymers that interact with APIs through hydrogen bonds and ionic interactions have been shown to restrict the molecular mobility of ASD systems in addition to their contribution in thermodynamic stability [11,32].…”

Compression Effects on Structural Relaxation Process of Amorphous Indomethacin

“…In experiments, the structural relaxation time, τ α , is typically measured by the broadband dielectric spectroscopy (BDS) technique [14][15][16]. The global atomic rearrangement causes a prominent, broad, and asymmetry α-peak on the dielectric loss spectra.…”

“…The global atomic rearrangement causes a prominent, broad, and asymmetry α-peak on the dielectric loss spectra. From these, one can capture a dramatic growth of τ α upon isobaric cooling or isothermal squeezing [14][15][16]. When τ α reaches 10 2 s, amorphous pharmaceutical systems undergo the glass transition and fall out of equilibrium.…”