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Impact of alternative solid state forms and specific surface area of high-dose, hydrophilic active pharmaceutical ingredients on tabletability
Paluch, Krzysztof J. Tajber, L. Corrigan, O.I. Healy, A.M.
Paluch, Krzysztof J.
Tajber, L.
Corrigan, O.I.
Healy, A.M.
Publication Date
2013-08
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This document is the Accepted Manuscript version of a Published Work
that appeared in final form in Molecular Pharmaceutics, copyright © 2013 American Chemical
Society after peer review and technical editing by the publisher. To access the final edited and
published work see http://dx.doi.org/10.1021/mp400124z
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openAccess
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2013-08-20
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Abstract
In order to investigate the effect of using different
solid state forms and specific surface area (TBET) of active
pharmaceutical ingredients on tabletability and dissolution
performance, the mono- and dihydrated crystalline forms of
chlorothiazide sodium and chlorothiazide potassium (CTZK)
salts were compared to alternative anhydrous and amorphous
forms, as well as to amorphous microparticles of chlorothiazide
sodium and potassium which were produced by spray drying and
had a large specific surface area. The tablet hardness and tensile
strength, porosity, and specific surface area of single-component,
convex tablets prepared at different compression pressures were characterized. Results confirmed the complexity of the
compressibility mechanisms. In general it may be concluded that factors such as solid-state form (crystalline vs amorphous), type
of hydration (presence of interstitial molecules of water, dehydrates), or specific surface area of the material have a direct impact
on the tabletability of the powder. It was observed that, for powders of the same solid state form, those with a larger specific
surface area compacted well, and better than powders of a lower surface area, even at relatively low compression pressures.
Compacts prepared at lower compression pressures from high surface area porous microparticles presented the shortest times to
dissolve, when compared with compacts made of equivalent materials, which had to be compressed at higher compression
pressures in order to obtain satisfactory compacts. Therefore, materials composed of nanoparticulate microparticles (NPMPs)
may be considered as suitable for direct compaction and possibly for inclusion in tablet formulations as bulking agents, APIs,
carriers, or binders due to their good compactibility performance
Version
Accepted manuscript
Citation
Paluch KJ, Tajber L, Corrigan OI et al (2013) Impact of alternative solid state forms and
specific surface area of high-dose, hydrophilic active pharmaceutical ingredients on tabletability.
Molecular Pharmaceutics. 10(10): 3628-3639.
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Article