Journal article
Investigation of Spatial Heterogeneity of Salt Disproportionation in Tablets by Synchrotron X‑ray Diffractometry
Molecular pharmaceutics, Vol.14(4), pp.1133-1144
04/03/2017
DOI: 10.1021/acs.molpharmaceut.6b01052
PMID: 28195490
Abstract
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 (pHeq) and extent of PioHCl disproportionation.
Details
- Title: Subtitle
- Investigation of Spatial Heterogeneity of Salt Disproportionation in Tablets by Synchrotron X‑ray Diffractometry
- Creators
- Sampada Koranne - Department of Pharmaceutics, College of PharmacyRamprakash Govindarajan - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of PharmacyRaj Suryanarayanan - Department of Pharmaceutics, College of Pharmacy
- Resource Type
- Journal article
- Publication Details
- Molecular pharmaceutics, Vol.14(4), pp.1133-1144
- Publisher
- American Chemical Society
- DOI
- 10.1021/acs.molpharmaceut.6b01052
- PMID
- 28195490
- ISSN
- 1543-8384
- eISSN
- 1543-8392
- Grant note
- DOI: 10.13039/100004343, name: 3M; name: William and Mildred Peters Endowment Fund
- Language
- English
- Date published
- 04/03/2017
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984065697802771
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