Better understanding of dissolution behaviour of amorphous drugs by in situ solid-state analysis using Raman spectroscopy

Monitoring the recrystallisation of amorphous xylitol using Raman spectroscopy and wide-angle X-ray scattering

“…Ueda et al (2014) found that the rate of crystallization of amorphous indomethacin was faster when measured using Raman compared with XRPD. They found that Raman has a lower level of detection than XRPD, possibly due to nano-crystalline material and crystal nuclei appearing amorphous using XRPD but are detectable using Raman, as also described by Savolainen et al (2009). Also Tian et al (2007) reported underestimation of the level of crystallinity of amorphous carbamazepine compacts using XRPD compared to Raman spectroscopy.…”

Formation, Physical Stability, and Quantification of Process-Induced Disorder in Cryomilled Samples of a Model Polymorphic Drug

“…12 This process represents an effective method of reducing the risk of recrystallisation of any amorphous materials produced due to the lower process temperatures involved compared to milling at ambient or higher temperatures, and it is often a more efficient way to prepare an amorphous API for those compounds which are disordered by milling. [13][14][15][16][17] Amorphous drugs are important as their greater surface area and surface activity can lead to higher bioavailability 18,19 and attempts have also been made to use the amorphous form of a drug to circumvent patents which apply to a crystalline form. 20 However, due to the metastable nature of amorphous drugs, the amorphous regions or crystal defects created by milling are unstable and under a range of circumstances such as elevated temperature or relative humidity, they undergo structural changes or revert to the original form or to other stable crystalline forms.…”

Stabilisation of amorphous furosemide increases the oral drug bioavailability in rats

“…At those temperatures, the molecular mobility of the drug is very low and therefore, the physical stability is high at these temperatures (Newman et al, 2011). The glass solution used in this study seemed stable during storage, but devitrification is often observed during dissolution (Kanaujia et al, 2011;Savolainen et al, 2009). In previous studies, it has been problematic to keep the ASSF in its amorphous form during dissolution at pH 6.5 (Nielsen et al, 2013b(Nielsen et al, , 2013c, and therefore, it is essential to investigate the solid state form of furosemide in the glass solution also during dissolution.…”