Selective Detection and Quantitation of Organic Molecule Crystallization by Second Harmonic Generation Microscopy

Wanapun, Duangporn; Kestur, Umesh S.; Kissick, David J.; Simpson, Garth J.; Taylor, Lynne S.

doi:10.1021/ac100564f

Cited by 68 publications

(85 citation statements)

References 48 publications

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“…Typical nonphase-matchable forward coherence lengths in APIs considering just dispersion alone are on the order of ∼5− 10 μm, 13 which is comparable to the depth of field. Under these conditions, the neglect of phase-matching could result in an error in the analysis of approximately an order of magnitude [i.e., ∼(20 μm/7 μm) 2 ].…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Ab Initio Prediction of the Diversity of Second Harmonic Generation from Pharmaceutically Relevant Materials

Toth

Schmitt

Snyder

et al. 2015

Crystal Growth & Design

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A model for predicting the anticipated second harmonic generation (SHG) activity of crystalline active pharmaceutical ingredients (APIs) was developed based on combining time-dependent Hartree−Fock calculations of the molecular building block with analytical theory for the predicted intensity from the lattice. Predicted trends agreed well overall with experimental measurements for 18 representative APIs. Inspection of the SHG images suggests that outliers from the predicted trends likely arose from the presence of trace SHG-active metastable crystal forms not considered in the predictions. The success of this relatively simple computational approach suggests a route for reliably predicting the anticipated SHG activities of API target molecules, which in turn can serve to indicate their potential compatibility with analysis by SHG.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Ab Initio Prediction of the Diversity of Second Harmonic Generation from Pharmaceutically Relevant Materials

Toth

Schmitt

Snyder

et al. 2015

Crystal Growth & Design

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“…The signals were amplified with Ortec 9305 amplifiers, directed into photon-counting cards (PMS− 400A, Becker and Hickl GmbH). The acquisition software utilized Labview, and the images acquired were analyzed using ImageJ software 35,36 . Five z-planes were acquired for each field of view of 600 × 600 µm with a 10×objective (Nikon 0.3 NA).…”

Section: Methodsmentioning

confidence: 99%

Water–solid interactions in amorphous maltodextrin-crystalline sucrose binary mixtures

Ghorab¹,

Toth

Simpson

et al. 2013

Pharmaceutical Development and Technology

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Amorphous and crystalline solids are commonly found together in a variety of pharmaceutical and food products. In this study, the influence of co-formulation of amorphous maltodextrins (MDs) and crystalline sucrose (S) on moisture sorption, deliquescence, and glass transition (Tg) properties of powder blends was investigated. Individual components and binary mixtures of four different molecular weight MDs with sucrose in 1:1 w/w ratios were exposed to various relative humidity (RH) environments and their equilibrium and dynamic moisture contents were monitored. The deliquescence point (RH0) and dissolution behavior of sucrose alone and in blends was also monitored by polarized light microscopy and second harmonic generation imaging. In S:MD blends, the deliquescence RH of sucrose was lower than the RH0 of sucrose alone, and synergistic moisture sorption also occurred at RHs lower than the RH0. Intimate contact of sucrose crystals with the amorphous MDs resulted in complete dissolution of sucrose at RH < RH0. When blends were stored at conditions exceeding the Tg of the individual MDs (25 °C and 60%, 49% and 34%RH for MD21, MD29 and MD40, respectively), the Tg of the blends was lower than that of individual MDs. Thus, co-formulation of amorphous MDs with crystalline sucrose sensitizes the blend to moisture, potentially leading to deleterious changes in the formulation if storage conditions are not adequately controlled.

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“…It is a useful tool for the examination of crystalline samples, allowing for high signal-to-noise measurements, with low limits of detection. 22–24 SHG involves the frequency-doubling of light upon interaction with certain classes of noncentrosymmetric crystals. 23 It has recently been applied to quantify crystallinity without the need for any additional sample processing.…”

Section: Resultsmentioning

confidence: 99%

Drop printing of pharmaceuticals: Effect of molecular weight on PEG coated‐naproxen/PEG 3350 solid dispersions

et al. 2015

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Solid dispersions have been used to enhance the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, the solid state phase, compositional uniformity, and scale-up problems are issues that need to be addressed. To allow for highly controllable products, the Drop Printing (DP) technique can provide precise dosages and predictable compositional uniformity of APIs in two/three dimensional structures. In this study, DP was used to prepare naproxen (NAP)/polyethylene glycol 3350 (PEG3350) solid dispersions with PEG coatings of different molecular weights (MW). A comparison of moisture-accelerated crystallization inhibition by different PEG coatings was assessed. Scanning electron microscopy (SEM), second harmonic generation (SHG) microscopy, and differential scanning calorimetry (DSC) analysis were performed to characterize the morphology and quantify the apparent crystallinity of NAP within the solid dispersions. Thermogravimetric analysis (TGA) was employed to measure the water content within each sample. The results suggest that the moisture-accelerated crystallization inhibition capability of the PEG coatings increased with increasing MW of the PEG coating. Besides, to demonstrate the flexibility of DP technology on manufacturing formulation, multilayer tablets with different PEG serving as barrier layers were also constructed, and their dissolution behavior was examined. By applying DP and appropriate materials, it is possible to design various carrier devices used to control the release dynamics of the API.

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Selective Detection and Quantitation of Organic Molecule Crystallization by Second Harmonic Generation Microscopy

Cited by 68 publications

References 48 publications

Ab Initio Prediction of the Diversity of Second Harmonic Generation from Pharmaceutically Relevant Materials

Ab Initio Prediction of the Diversity of Second Harmonic Generation from Pharmaceutically Relevant Materials

Water–solid interactions in amorphous maltodextrin-crystalline sucrose binary mixtures

Drop printing of pharmaceuticals: Effect of molecular weight on PEG coated‐naproxen/PEG 3350 solid dispersions

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