Investigation of Solid Phase Composition on Tablet Surfaces by Grazing Incidence X-ray Diffraction

Koradia, Vishal; Tenho, Mikko; Diego, Heidi Lopez de; Ringkjøbing-Elema, Michiel; Møller-Sonnergaard, Jørn; Salonen, Jarno; Lehto, Vesa‐Pekka; Rantanen, Jukka

doi:10.1007/s11095-011-0520-8

Cited by 14 publications

(10 citation statements)

References 42 publications

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“…This process will be facilitated by the intrinsic nature of the lubricant. , As a result of compression, PioHCl and MgSt particles come into intimate physical contact, increasing the interface between particles. In addition, compression can introduce significant lattice disorder. , The sorption of water in these “disordered regions” can cause pronounced plasticization, resulting in increased molecular mobility, and will enhance the reaction rate.…”

Section: Results and Discussionmentioning

confidence: 99%

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Investigation of Spatial Heterogeneity of Salt Disproportionation in Tablets by Synchrotron X-ray Diffractometry

2017

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Tablets which were binary mixtures of pioglitazone hydrochloride (PioHCl) with magnesium stearate (MgSt), croscarmellose sodium (CCS), microcrystalline cellulose, or lactose monohydrate were prepared. Two sets of experiments, using intact tablets, were performed. (i) Tablets containing PioHCl (90% w/w) and MgSt were exposed to 25 or 40 °C and 75% RH in a custom-built temperature/humidity chamber. In situ spatiotemporal mapping of disproportionation was performed by transmission-mode synchrotron X-ray diffractometry (SXRD; Argonne National Laboratories). Tablets were scanned in radial direction starting from the top edge of the tablet and moving, in increments of 300 μm, toward the center. There was evidence of disproportionation after 10 min (at 40 °C). The reaction was initiated on the tablet surface and progressed toward the core. (ii) SXRD of tablets stored for a longer time (up to 15 days) enabled the simultaneous quantification of the reactants and products of disproportionation and provided insight into the reaction progression. The influence of sorbed water and microenvironmental acidity on the disproportionation reaction was investigated. The most pronounced reaction was observed in the presence of MgSt followed by CCS. The transformation was solution-mediated, and the spatial heterogeneity in disproportionation could be explained by the migration of sorbed water. There was a good correlation between microenvironmental acidity (pH) and extent of PioHCl disproportionation.

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Section: Results and Discussionmentioning

confidence: 99%

“…In addition, compression can introduce significant lattice disorder. 30,31 The sorption of water in these "disordered regions" can cause pronounced plasticization, resulting in increased molecular mobility, and will enhance the reaction rate.…”

Section: Molecular Pharmaceuticsmentioning

confidence: 99%

Investigation of Spatial Heterogeneity of Salt Disproportionation in Tablets by Synchrotron X-ray Diffractometry

2017

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“…At compression pressures relevant to commercial tablet manufacture, partial amorphization was observed in tablets of theophylline, nitrofurantoin, and amlodipine besylate. 8 On the other hand, compression of amorphous drugs such as indomethacin, sucrose, celecoxib caused its crystallization. [9][10][11] Crystallization was most pronounced on the radial tablet surface, which comes in contact with die wall and was attributed to die wall friction.…”

Section: Introductionmentioning

confidence: 99%

Compression-Induced Polymorphic Transformation in Tablets: Role of Shear Stress and Development of Mitigation Strategies

Thakral

Stephenson

et al. 2019

Journal of Pharmaceutical Sciences

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a b s t r a c tOur goals were to evaluate the effects of (i) hydrostatic pressure alone and (ii) its combined effect with shear stress during compaction, on the polymorphic transformation (form C / A) of a model drug, chlorpropamide. The powder was either subjected to hydrostatic pressure in a pressure vessel or compressed in a tablet press, at pressures ranging from 25 to 150 MPa. The overall extent of phase transformation was determined by powder X-ray diffractometry, whereas 2D-X-ray diffractometry enabled quantification of the spatial distribution of phase composition in tablets. Irrespective of the pressure, the extent of transformation following compaction was higher than that because of hydrostatic pressure alone, the difference attributed to the contribution of shear stress experienced during compaction. At a compression pressure of 25 MPa, there was a pronounced gradient in the extent of phase transformation when monitored from radial tablet surface to core. This gradient decreased with increase in compression pressure. Four approaches were attempted to minimize the effect of compression-induced phase transformation: (a) site-specific lubrication, (b) use of a viscoelastic excipient, (c) ceramic-lined die, and (d) use of cavity tablet. The ceramic-lined die coupled with site-specific lubrication was most effective in minimizing the extent of compression-induced phase transformation.

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“…For a given tablet formulation composition, the incident angle of the X-rays (with the tablet surface) will dictate the depth of penetration. Thus, by modulating the incident angle, it is possible to characterize different regions (depths) from the tablet surface (glancing angle X-ray diffractometry). − A microdiffractometer fitted with a two-dimensional area detector is well suited for this purpose. , Data collection time with this setup is usually several orders of magnitude shorter than with conventional instruments. Second, since a substantial part of the diffraction ring is collected, errors due to preferred orientation can be significantly reduced.…”

Section: Introductionmentioning

confidence: 99%

Spatial Distribution of Trehalose Dihydrate Crystallization in Tablets by X-ray Diffractometry

Thakral

Yamada²,

Stephenson

et al. 2015

Mol. Pharmaceutics

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Crystallization of trehalose dihydrate (C12H22O11·2H2O) was induced by storing tablets of amorphous anhydrous trehalose (C12H22O11) at 65% RH (RT). Our goal was to evaluate the advantages and limitations of two approaches of profiling spatial distribution of drug crystallization in tablets. The extent of crystallization, as a function of depth, was determined in tablets stored for different time-periods. The first approach was glancing angle X-ray diffractometry, where the penetration depth of X-rays was modulated by the incident angle. Based on the mass attenuation coefficient of the matrix, the depth of X-ray penetration was calculated as a function of incident angle, which in turn enabled us to "calculate" the extent of crystallization to different depths. In the second approach, the tablets were split into halves and the split surfaces were analyzed directly. Starting from the tablet surface and moving toward the midplane, XRD patterns were collected in 36 "regions", in increments of 0.05 mm. The results obtained by the two approaches were, in general, in good agreement. Additionally, the results obtained were validated by determining the "average" crystallization in the entire tablet by using synchrotron radiation in the transmission mode. The glancing angle method could detect crystallization up to ∼650 μm and had a "surface bias". Being a nondestructive technique, this method will permit repeated analyses of the same tablet at different time points, for example, during a stability study. However, split tablet analyses, while a "destructive" technique, provided comprehensive and unbiased depth profiling information.

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Investigation of Solid Phase Composition on Tablet Surfaces by Grazing Incidence X-ray Diffraction

Abstract: With GIXD measurements, it was possible to probe the solid form composition at the different depths of the tablet surfaces and to obtain depth-dependent information on the compaction-induced amorphization, crystal disordering and dehydration.

Cited by 14 publications

References 42 publications

Investigation of Spatial Heterogeneity of Salt Disproportionation in Tablets by Synchrotron X-ray Diffractometry

Investigation of Spatial Heterogeneity of Salt Disproportionation in Tablets by Synchrotron X-ray Diffractometry

Compression-Induced Polymorphic Transformation in Tablets: Role of Shear Stress and Development of Mitigation Strategies

Spatial Distribution of Trehalose Dihydrate Crystallization in Tablets by X-ray Diffractometry

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