Applications of Dynamic Mechanical Analysis in the Engineering of Amorphous Solid Dispersions

Abstract

<jats:title>Abstract</jats:title><jats:p>Dynamic mechanical analysis (DMA) offers several advantages over prevailing methods in the characterization of amorphous solid dispersions (ASDs) typically used for improving the delivery of poorly water-soluble drugs. This method of analysis, though underutilized in the study of pharmaceutical systems, is particularly attuned to rheological investigations of thermal and mechanical properties of solids such as ASDs. Its ability to determine the viscoelastic properties of systems across a wide range of temperatures and shear conditions provides useful insight for the development and processing of ASDs. The response of materials to an imposed stress, captured by DMA, can help identify proper conditions for preparing homogenous extrudates of the polymer and active pharmaceutical ingredient through hot melt extrusion (HME). As HME continues to gain utility within the pharmaceutical industry, the ability to tailor process conditions will become increasingly important for the efficient design and production of ASD products for poorly water-soluble drugs. Furthermore, DMA can be used to probe molecular mobility and its link to physical stability of ASDs. Establishing the link between molecular mobility and crystallization kinetics is central to predicting the physical stability of ASDs. Therefore, increasing the understanding of material properties through DMA will enable the successful development of more stable amorphous drug products. This review summarizes current characterization tools for ASDs and discusses the potential of utilizing DMA as a robust alternative to traditional methods.</jats:p>

Amorphous Solid Dispersions (ASDs): The Influence of Material Properties, Manufacturing Processes and Analytical Technologies in Drug Product Development

“…The Dynamic Mechanical Analyzer (DMA) is commonly used for this purpose. Small cycling loads are applied on the samples enabling determination of viscous and elastic components of the complex modulus and by simultaneous temperature variation an exact T g value can be obtained [ 68 , 85 ]. The technique can also be adapted with a chamber for relative humidity variation which enables assessment of humidity and its plasticizing effects.…”

“…The technique can also be adapted with a chamber for relative humidity variation which enables assessment of humidity and its plasticizing effects. DMA is ideally suited for evaluation of HME extrudates [ 85 ], but also used for thin film ASD prepared by solvent evaporation. DMA can be used for identification of proper HME process parameters to obtain homogenous extrudates and to assess molecular mobility which can be linked to ASD physical stability [ 85 ].…”

Complementarity of mDSC, DMA, and DRS Techniques in the Study of Tg and Sub-Tg Transitions in Amorphous Solids: PVPVA, Indomethacin, and Amorphous Solid Dispersions Based on Indomethacin/PVPVA

“…It has been found that DMA is able to detect amorphous phase domains as small as 10 nm, and thus, it is a useful technique to characterize solid dispersions . Moreover, in terms of controlling measurement conditions such as humidity, temperature, and frequency, DMA is more flexible than other conventional techniques, such as traditional rheology, to study ASDs . Earlier, using DMA to study the molecular relaxations in ASDs had some problems: (i) it is difficult to mount powder; (ii) it needs a special sample geometry; (iii) ASDs with high drug loadings are brittle and hence inappropriate for DMA analysis. , However, the DMA analyzer with a novel powder sample holder used in the present study helps us to completely eliminate these bottlenecks.…”