TY - JOUR
T1 - Spatial distribution of trehalose dihydrate crystallization in tablets by x-ray diffractometry
AU - Thakral, Naveen K.
AU - Yamada, Hiroyuki
AU - Stephenson, Gregory A.
AU - Suryanarayanan, Raj
N1 - Publisher Copyright:
© 2015 American Chemical Society.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2015/10/5
Y1 - 2015/10/5
N2 - 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.
AB - 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.
KW - Amorphous
KW - Crystallization
KW - Physical characterization
KW - Tablet
KW - X-ray powder diffractometry
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U2 - 10.1021/acs.molpharmaceut.5b00567
DO - 10.1021/acs.molpharmaceut.5b00567
M3 - Article
C2 - 26332906
AN - SCOPUS:84986626881
VL - 12
SP - 3766
EP - 3775
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 10
ER -