Stability of indomethacin with relevance to the release from amorphous solid dispersions studied with ATR-FTIR spectroscopic imaging

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

“…Some of the reasons given for excipient selection included reliance on previous reports of the use of similar excipients and their historical applicability in ASDs and oral dosage forms (100–125); the physicochemical properties and functions of the excipient, possible interactions between the compound and the excipient, and the miscibility/immiscibility of the compound and excipient (105–108,111,112,114,126–148); the processability or suitability of the excipient for the preparation method (73,105,119,127,149–152); and the possibility of designing a controlled-release profile and/or pH-dependent release of the compound from the amorphous formulation (99,100,107,123,153–156). An attempt to tailor and customize excipients by modifying the functional groups which could be potentially used in ASD formulations has also been reported (157).…”

The Combined Use of Imaging Approaches to Assess Drug Release from Multicomponent Solid Dispersions

“…To this end, it is beneficial to combine standard USP-type dissolution tests with chemically specific, spectroscopic imaging-based analytical approaches such as attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic imaging (21–24), magnetic resonance imaging (MRI) (25,26), UV imaging (27,28) and Raman imaging (29,30). These techniques allow the visualization of dynamic physico-chemical processes within a tablet under dissolution conditions, making it possible to elucidate phenomena that could not be easily identifiable from the USP release curve.…”

Comparison of pharmaceutical formulations: ATR-FTIR spectroscopic imaging to study drug-carrier interactions

“…For example, the spectral band used for indomethacin is 1250-1200 cm À1 which is characteristic of the amorphous form. Under certain experimental conditions indomethacin can recrystallize to its preferable lower energetic state g-or a-form (Ewing et al, 2014). As a result, an absorption band for the a-crystalline form was identified at 1760-1720 cm À1 .…”

“…ATR-FTIR spectroscopic imaging provides chemically specific information about the tablet compacts as well as spatially resolved spectroscopic images showing the distribution of the individual components within the measured area (Chan and Kazarian, 2004;Kazarian and Chan, 2003;Kazarian and Ewing, 2013). This spectroscopic imaging approach has proven a versatile tool for the study of fast dynamic systems providing information about physical and structural changes to the measured samples (Ewing et al, 2014;Kimber et al, 2014). In situ tablet dissolution experiments have previously been demonstrated using this approach where spectroscopic images were recorded as the experiment progressed (Kazarian and Ewing, 2013;van der Weerd and Kazarian, 2005).…”

“…Changing the physical state of indomethacin to the amorphous form is commonly employed as a means to increase the rate of release of the drug into the system and factors that prevent crystallisation and stabilise the amorphous form are of great interest (Ewing et al, 2014;Kaminska et al, 2014;Karmwar et al, 2011;Surwase et al, 2013). Indomethacin has been used as a model poorly watersoluble drug in a number of investigations where co-complexes between the drug and carrier have been achieved via hydrogen bonded interactions (Majumder et al, 2013;Maruyoshi et al, 2012).…”