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- Title
Effect of ball milling on the physicochemical properties of atorvastatin calcium sesquihydrate: the dissolution kinetic behaviours of milled amorphous solids.
- Authors
Kobayashi, Makiko; Hattori, Yusuke; Sasaki, Tetsuo; Otsuka, Makoto
- Abstract
Objectives The purposes of this study were to clarify the amorphization by ball milling of atorvastatin calcium sesquihydrate ( AT) and to analyse the change in dissolution kinetics. Methods The amorphous AT was prepared from crystal AT by ball milling and analysed in terms of the changes of its physicochemical properties by powder X-ray diffraction analysis ( XRD), thermal analysis and infrared spectroscopy ( IR). Moreover, to evaluate the usefulness of the amorphous form for pharmaceutical development, intrinsic solubility of the ground product was evaluated using a dissolution kinetic method. Key findings The XRD results indicated that crystalline AT was transformed into amorphous solids by more than 30-min milling. The thermal analysis result suggested that chemical potential of the ground AT are changed significantly by milling. The IR spectra of the AT showed the band shift from the amide group at 3406 cm−1 with an intermolecular hydrogen bond to a free amide group at 3365 cm−1 by milling. The dissolution of amorphous AT follows a dissolution kinetic model involving phase transformation. Conclusions The initial dissolution rate of the ground product increased with the increase in milling time to reflect the increase in the intrinsic solubility based on the amorphous state.
- Subjects
ATORVASTATIN; CALCIUM; DISSOLUTION (Chemistry); X-ray diffraction; ANALYTICAL mechanics
- Publication
Journal of Pharmacy & Pharmacology, 2017, Vol 69, Issue 1, p15
- ISSN
0022-3573
- Publication type
Article
- DOI
10.1111/jphp.12636