Nanoscale Mid-Infrared Imaging of Phase Separation in a Drug–Polymer Blend

Eerdenbrugh, Bernard Van; Lo, Michael; Kjoller, Kevin; Marcott, Curtis; Taylor, Lynne S.

doi:10.1002/jps.23099

Cited by 82 publications

(89 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For amorphous solid dispersions, where an amorphous drug is intimately mixed with a polymeric carrier, formation of miscible systems is desired as it increases the physical stability of the system. Two model systems for polymer-polymer 43 and drug-polymer 44 miscibility were examined and are reviewed below. Dextran-Poly(vinylpyrrolidone) Blends.…”

Section: Miscibility In Pharmaceutical Blend Formulationsmentioning

confidence: 99%

“…As local topography and mechanical properties can also influence the spectroscopic intensities measured in single-wavelength images, it is good practice to confirm the interpretation by generating ratio images. 43,44 When the ratio image of 1280:1350 cm -1 (shown in Fig. 20D) is compared with the topographical image in Fig.…”

Section: Miscibility In Pharmaceutical Blend Formulationsmentioning

confidence: 99%

“…In addition, the state of drug dispersion can change over time, either during storage or on drug release. 44 A model drug-polymer blend system composed of felodipine and poly(acrylic acid) (PAA) was examined with AFM-IR. 44 When prepared as an amorphous solid by solvent evaporation, felodipine has relatively low crystallization tendency; 47,48 therefore, it serves as a good model compound to evaluate drugpolymer miscibility, because it can be assumed that the drug will remain amorphous.…”

Section: Miscibility In Pharmaceutical Blend Formulationsmentioning

confidence: 99%

“…21. 44 The average thickness of the film was approximately 570 nm. Locations where spectra were taken are marked on the images and correspond to discrete domains (1-4, marked in red) and the continuous phase (5-8, marked in green).…”

Section: Miscibility In Pharmaceutical Blend Formulationsmentioning

confidence: 99%

See 3 more Smart Citations

AFM–IR: Combining Atomic Force Microscopy and Infrared Spectroscopy for Nanoscale Chemical Characterization

Dazzi

Prater²,

Hu³

et al. 2012

Appl Spectrosc

Self Cite

474

444

View full text Add to dashboard Cite

Polymer and life science applications of a technique that combines atomic force microscopy (AFM) and infrared (IR) spectroscopy to obtain nanoscale IR spectra and images are reviewed. The AFM–IR spectra generated from this technique contain the same information with respect to molecular structure as conventional IR spectroscopy measurements, allowing significant leverage of existing expertise in IR spectroscopy. The AFM–IR technique can be used to acquire IR absorption spectra and absorption images with spatial resolution on the 50 to 100 nm scale, versus the scale of many micrometers or more for conventional IR spectroscopy. In the life sciences, experiments have demonstrated the capacity to perform chemical spectroscopy at the sub-cellular level. Specifically, the AFM–IR technique provides a label-free method for mapping IR-absorbing species in biological materials. On the polymer side, AFM–IR was used to map the IR absorption properties of polymer blends, multilayer films, thin films for active devices such as organic photovoltaics, microdomains in a semicrystalline polyhydroxyalkanoate copolymer, as well as model pharmaceutical blend systems. The ability to obtain spatially resolved IR spectra as well as high-resolution chemical images collected at specific IR wavenumbers was demonstrated. Complementary measurements mapping variations in sample stiffness were also obtained by tracking changes in the cantilever contact resonance frequency. Finally, it was shown that by taking advantage of the ability to arbitrarily control the polarization direction of the IR excitation laser, it is possible to obtain important information regarding molecular orientation in electrospun nanofibers.

show abstract

Section: Miscibility In Pharmaceutical Blend Formulationsmentioning

confidence: 99%

Section: Miscibility In Pharmaceutical Blend Formulationsmentioning

confidence: 99%

Section: Miscibility In Pharmaceutical Blend Formulationsmentioning

confidence: 99%

Section: Miscibility In Pharmaceutical Blend Formulationsmentioning

confidence: 99%

See 2 more Smart Citations

AFM–IR: Combining Atomic Force Microscopy and Infrared Spectroscopy for Nanoscale Chemical Characterization

Dazzi

Prater²,

Hu³

et al. 2012

Appl Spectrosc

Self Cite

474

444

View full text Add to dashboard Cite

show abstract

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

Abstract. Atomic force microscopy (AFM) and modulated differential scanning calorimetry (mDSC) were used to evaluate the extent of mixing of a hot melt extrusion process for producing solid dispersions of copovidone and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS 1000). In addition to composition, extrusion process parameters of screw speed and thermal quench rate were varied. The data indicated that for 10% TPGS and 300 rpm screw speed, the mixing was insufficient to yield a singlephase amorphous material. AFM images of the extrudate cross section for air-cooled material indicate round domains 200 to 700 nm in diameter without any observed alignment resulting from the extrusion whereas domains in extrudate subjected to chilled rolls were elliptical in shape with uniform orientation. Thermal analysis indicated that the domains were predominantly semi-crystalline TPGS. For 10% TPGS and 600 rpm screw speed, AFM and mDSC data were consistent with that of a single-phase amorphous material for both thermal quench rates examined. When the TPGS concentration was reduced to 5%, a single-phase amorphous material was achieved for all conditions even the slowest screw speed studied (150 rpm).

show abstract

Solid‐State Characterization of Amorphous Dispersions

Vogt¹

2015

Pharmaceutical Sciences Encyclopedia

View full text Add to dashboard Cite

This chapter reviews established and emerging analytical and physical techniques for the characterization of amorphous solid dispersions. The thermal analysis methods used in most reported studies of amorphous solid dispersions include differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and isothermal microcalorimetry (ITC). Many of the commonly used polymers in amorphous solid dispersions are hydrophilic in nature and contain polar functional groups, and can absorb moisture from the atmosphere. In the pharmaceutical sciences, vibrational spectroscopic methods are generally used to probe molecular vibrations and phonon modes in crystalline substances. Solid‐state nuclear magnetic resonance (SSNMR) analysis of mobility in amorphous solid dispersions is complementary to thermal analysis and dielectric spectroscopy techniques. Scanning electron microscopy (SEM) is widely used in the characterization of amorphous solid dispersions. Effective characterization plays a critical role in the development of pharmaceutical amorphous solid dispersions.

show abstract

Nanoscale Mid-Infrared Imaging of Phase Separation in a Drug–Polymer Blend

Cited by 82 publications

References 31 publications

AFM–IR: Combining Atomic Force Microscopy and Infrared Spectroscopy for Nanoscale Chemical Characterization

AFM–IR: Combining Atomic Force Microscopy and Infrared Spectroscopy for Nanoscale Chemical Characterization

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

Solid‐State Characterization of Amorphous Dispersions

Contact Info

Product

Resources

About