Evaluation of Effects of Pharmaceutical Processing on Structural Disorders of Active Pharmaceutical Ingredient Crystals Using Nanoindentation and High-Resolution Total Scattering Pair Distribution Function Analysis

Chen, Shuang; Sheikh, Ahmad Y.; Ho, Raimundo

doi:10.1002/jps.24178

Cited by 27 publications

(23 citation statements)

References 43 publications

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“…This was evaluated using the synchrotron-based high resolution total scattering pair distribution function analysis. No structural disorders were observed under typical milling and compaction conditions for the hard and brittle compound 1, whereas soft crystals of compound 2 exhibited obvious disorders even under mild milling and compaction conditions (103). It was recently reported that H can be used as an effective parameter that correlates well with the solubility of compounds.…”

Section: Mechanical Properties Of Molecular Crystalsmentioning

confidence: 99%

Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients

2016

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Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients # Nanoindentation allows quantitative determination of a material's response to stress such as elastic and plastic deformation or fracture tendency. Key instruments that have enabled great advances in nanomechanical studies are the instrumented nanoindenter and atomic force microscopy. The versatility of these instruments lies in their capability to measure local mechanical response, in very small volumes and depths, while monitoring time, displacement and force with high accuracy and precision. This review highlights the application of nanoindentation for mechanical characterization of pharmaceutical materials in the preformulation phase (primary investigation of crystalline active ingredients and excipients). With nanoindentation, mechanical response can be assessed with respect to crystal structure. The technique is valuable for mechanical screening of a material at an early development phase in order to predict and better control the processes in which a material is exposed to stress such as milling and compression.

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Section: Mechanical Properties Of Molecular Crystalsmentioning

confidence: 99%

Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients

2016

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“…Pharmaceutical manufacturing of drug products containing crystalline active pharmaceutical ingredients (APIs) involve multiple unit operations, including crystallization, filtration, drying, milling, blending, granulation and compression, to name but some. In each of these unit operations, energy is imparted on the crystals in various forms most prominently as mechanical and thermal energy (Chen et al, 2014). It is well documented that the pharmaceutical unit processes can generate various types of defects in API crystals (Dialer & Kuesner, 1973;Saleki-Gerhardt et al, 1994;Ward & Schultz, 1995;Koivisto et al, 2006;Chan & Doelker, 1985).…”

Section: Stress-induced Transformations In the Context Of Pharmaceutimentioning

confidence: 99%

Polymorphism and surface diversity arising from stress-induced transformations – the case of multicomponent forms of carbamazepine

Rauber¹,

Arhangelskis²,

Bond³

et al. 2021

Acta Crystallogr B Struct Sci Cryst Eng Mater

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Stress-induced transformations of labile multicomponent organic solids may have a significant impact on industrial manufacturing processes, for example, in the pharmaceutical field. This study considers 15 carbamazepine (CBZ) multicomponent crystal forms, with the aim of identifying the structural and surface features that drive the outcome of thermal stress-induced transformations. Analysis of the crystal structures, and specifically the degree of similarity with the CBZ polymorphs produced by desolvation-like processes, identifies some degree of correlation between structural features. In particular, mutually exclusive supramolecular motifs identified previously within CBZ crystal structures are frequently (but not invariably) preserved, and thereby provide some indication of the anticipated polymorphic outcome. This is broadly consistent with established models relating reactant and product crystal phases. Some of the CBZ multicomponent materials show surface modifications indicative of the formation of a liquid intermediate phase, which provides an alternative dissolution/recrystallization mechanism and different polymorphic outcomes compared to the direct solid–solid transformation pathway. Other cases show intermediates of varying stoichiometry and instances of chemical decomposition. Hence, the product of thermal decomposition is frequently affected by the physical properties of the coformer, such as boiling point and reactivity. This can lead to a dependence on experimental conditions, especially when events such as recrystallization, chemical decomposition of the coformer, solubilization and peritectic melting occur concomitantly. This study highlights that the overall picture is complex, even within this series of closely related materials.

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“…In analysis of synchrotron-derived data, PCA is most widely used in X-ray absorption spectroscopies (XAS) (Fernandez-Garcia et al, 1995;Coulston et al, 1997;Wasserman et al, 1996Wasserman et al, , 1999Wasserman, 1997), although in two recent examples it was applied to assess phase separation pharmaceuticals using PDF data (Chieng et al, 2013;Chen et al, 2014). In XAS, it is routinely used to determine the number and/or relative concentration of discrete species (e.g.…”

Section: Introductionmentioning

confidence: 99%

Applications of principal component analysis to pair distribution function data

2015

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Developments in X‐ray scattering instruments have led to unprecedented access to in situ and parametric X‐ray scattering data. Deriving scientific insights and understanding from these large volumes of data has become a rate‐limiting step. While formerly a data‐limited technique, pair distribution function (PDF) measurement capacity has expanded to the point that the method is rarely limited by access to quantitative data or material characteristics – analysis and interpretation of the data can be a more severe impediment. This paper shows that multivariate analyses offer a broadly applicable and efficient approach to help analyse series of PDF data from high‐throughput and in situ experiments. Specifically, principal component analysis is used to separate features from atom–atom pairs that are correlated – changing concentration and/or distance in concert – allowing evaluation of how they vary with material composition, reaction state or environmental variable. Without requiring prior knowledge of the material structure, this can allow the PDF from constituents of a material to be isolated and its structure more readily identified and modelled; it allows one to evaluate reactions or transitions to quantify variations in species concentration and identify intermediate species; and it allows one to identify the length scale and mechanism relevant to structural transformations.

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Evaluation of Effects of Pharmaceutical Processing on Structural Disorders of Active Pharmaceutical Ingredient Crystals Using Nanoindentation and High-Resolution Total Scattering Pair Distribution Function Analysis

Cited by 27 publications

References 43 publications

Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients

Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients

Polymorphism and surface diversity arising from stress-induced transformations – the case of multicomponent forms of carbamazepine

Applications of principal component analysis to pair distribution function data

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