Partial Characterization of Different Mixtures of Solids by Measuring the Optical Nonlinear Response

Nonlinear Optical Imaging for Sensitive Detection of Crystals in Bulk Amorphous Powders

“…The high sensitivity of SONICC for detection of crystallinity relative to the other techniques is further highlighted by the ability to detect crystals even in the presence of 99.9% polymer. This observation is in agreement with the work of Rades and coworkers,21 who showed that for PVP–enalapril maleate form II mixtures, the ensemble‐averaged limit of detection was calculated to be 0.12% (1.2 parts per thousand). By using femtosecond laser sources and optimizing imaging instrumentation targeting this application, SONICC has significantly improved on those detection limits 33.…”

“…The second‐order nonlinear optical process has been of some interest in the pharmaceutical sciences for protein screening and chiral crystallization 18–20. There have been limited studies focused on exploring the utility of SHG for characterization of pharmaceutical solids 21–25. Rades and coworkers21–23 used SHG to distinguish and quantify polymorphism with the limit of detection calculated to be <5%.…”

“…There have been limited studies focused on exploring the utility of SHG for characterization of pharmaceutical solids 21–25. Rades and coworkers21–23 used SHG to distinguish and quantify polymorphism with the limit of detection calculated to be <5%. In addition, the researchers also used SHG to quantify crystallinity in binary mixtures of polyvinylpyrrolidone (PVP) with enalapril maleate and ranitidine hydrochloride with high sensitivity.…”

Relevance of the Second Harmonic Generation to Characterize Crystalline Samples

“…First-order squaric acid [45] 2,3-dichloroquinizarin [46] HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) [47] TATB (1,3,5-triamino-2,4,6-trinitrobenzene) [48] [(H 3 N(CH 2 )2SS(CH 2 )2NH 3 )PbI 5 ]ÁH 2 O [49] [C(NH2) 3 ]4Cl 2 SO 4 [50] (H 3 N(CH 2 ) 2 -S-S(CH 2 )2NH 3 )BiI 5 [51] 3-hydroxybenzoic acid [33,38] Orderdisorder triglycine sulfate [52] triazoyl ketone derivatives [53] P-SHG in-situ study of crystallization in a 390-mL stirring batch [54] quantification of structural and chemical purity [55,56] quantification of API in powdered and tableted samples [57] monitoring of pressure-induced transition [58] SHGM determination of the 3D orientation of organic nanocrystals embedded in a sol-gel matrix and distinction between monocrystalline and polycrystalline domains [59] determination of the degree of crystallinity in polymer mixtures; observation of the solid microstructure [60] detection of a metastable non-centrosymmetric polymorphic form in a chiral material; monitoring of nucleation and crystal growth; combination of several microscopic techniques [61,62] imaging of a pharmaceutical system involving several nonlinear optical processes [63] study of crystallinity and crystallization in an API/polymer mixture or in a pure API [64,65] selective imaging of API in powdered blends [66] crystallographic point group determination [67,68] study of growth-induced polarity formation [69] detection of a metastable non-centrosymmetric polymorphic form in a chiral material; confirmation of Ostwald's rule of stages; determination of the structural purity [70] development of SHGM at video rate [71] study of the organization of crystalline organic material inside an organic matrix [72] prediction of nonlinear optical responses from organic molecules [73,…”

Towards characterization and identification of solid state pharmaceutical mixtures through second harmonic generation

“…The relevant aspects of nonlinear optical theory are not repeated here but can be found in a previous paper,12 which describes work earlier performed in our group using the nonlinear optical technique. In this paper, we report on a new and enhanced, computer‐automated device, which has the ability to perform nonlinear optical measurements with improved speed and limits of detection.…”