Rapid Assessment of Homogeneity and Stability of Amorphous Solid Dispersions by Atomic Force Microscopy—From Bench to Batch

Abstract

PurposeTo verify the robustness and fundamental value of Atomic Force Microscopy (AFM) and AFM-based assays to rapidly examine the molecular homogeneity and physical stability of amorphous solid dispersions on Hot-Melt-Extrudates.MethodsAmorphous solid dispersions were prepared with a Hot-Melt Extruder (HME) and profiled by Raman Microscopy and AFM following a sequential analytical routine (Multi-Scale-Imaging-of-Miscibiliy (MIMix)). Extrudates were analyzed before and after incubation at elevated temperature and humidity. The data were compared with published results as collected on miniaturized melt models. The value of molecular phase separation rates for long term stability prediction was assessed.ResultsData recorded on the extrudates are consistent with those published, and they can be compared side by side. Such direct data comparisons allow the identification of possible sources of extrudate heterogeneities. The surface roughness analysis of fracture-exposed interfaces is a novel quantitative way to trace on the nanometer scale the efficiencies of differently conducted HME-processes. Molecular phase separation rates are shown to be relevant for long term stability predictions.ConclusionsThe AFM-based assessment of API:excipient combinations is a robust method to rapidly identify miscible and stable solid dispersions in a routine manner. It provides a novel analytical tool for the optimization of HME processes.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-013-1045-0) contains supplementary material, which is available to authorized users.

Assessing Mixing Quality of a Copovidone-TPGS Hot Melt Extrusion Process with Atomic Force Microscopy and Differential Scanning Calorimetry

“…For example, Lauer et al have used AFM to characterize the homogeneity of drug-polymer mixtures prepared using a microhot melt extruder (16) and compared the data to dispersions prepared using a screening method involving solvent casting. Qi and Craig have utilized AFM coupled with local thermal analysis as well as photothermal Fourier-transform infrared (PT-FTIR) microspectroscopy to characterize their drug-loaded hot melt extrudates (25).…”

“…The technique has been used widely in the polymer field (5) over the past two decades for evaluating systems such as polymer blends (6,7), block copolymers (8,9), and nanocomposites (10,11). Beyond the polymer and plastic industries, the technique has been gaining popularity within the pharmaceutical field for the characterization of amorphous solid dispersions (12)(13)(14)(15)(16).…”

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