title: Thermal Analysis by Structural Characterization as a Method for Assessing Heterogeneity in Complex Solid Pharmaceutical Dosage Forms.
abstract: Characterizing inter- and intrasample heterogeneity of solid and semisolid pharmaceutical products is important both for rational design of dosage forms and subsequent quality control during manufacture; however, most pharmaceutical products are multicomponent formulations that are challenging in this regard. Thermal analysis, in particular differential scanning calorimetry, is commonly used to obtain structural information, such as degree of crystallinity, or identify the presence of a particular polymorph, but the results are an average over the whole sample; it cannot directly provide information about the spatial distribution of phases. This study demonstrates the use of a new thermo-optical technique, thermal analysis by structural characterization (TASC), that can provide spatially resolved information on thermal transitions by applying a novel algorithm to images acquired by hot stage microscopy. We determined that TASC can be a low cost, relatively rapid method of characterizing heterogeneity and other aspects of structure. In the examples studied, it was found that high heating rates enabled screening times of 3-5 min per sample. In addition, this study demonstrated the higher sensitivity of TASC for detecting the metastable form of polyethylene glycol (PEG) compared to conventional differential scanning calorimetry (DSC). This preliminary work suggests that TASC will be a worthwhile additional tool for characterizing a broad range of materials.
authors.affiliation: School of Pharmacy, University of East Anglia , Norwich, Norfolk, United Kingdom , NR4 7TJ.|College of Pharmacy, University of Basrah , Basrah, Iraq.
authors.forename: Muqdad
authors.initials: M
authors.lastname: Alhijjaj
authors.affiliation: Department of Chemical Sciences, University of Huddersfield , Queensgate, Huddersfield, United Kingdom , HD1 3DH.
authors.forename: Mike
authors.initials: M
authors.lastname: Reading
authors.affiliation: School of Chemistry, University of East Anglia , Norwich, Norfolk United Kingdom , NR4 7TJ.
authors.forename: Peter
authors.initials: P
authors.lastname: Belton
authors.affiliation: School of Pharmacy, University of East Anglia , Norwich, Norfolk, United Kingdom , NR4 7TJ.
authors.forename: Sheng
authors.initials: S
authors.lastname: Qi
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004304:Dosage Forms; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D004304:Dosage Forms; D004364:Pharmaceutical Preparations