Polymorph Transformation in Paracetamol Monitored by In-line NIR Spectroscopy During a Cooling Crystallization Process

Abstract

The reliable in-line monitoring of pharmaceutical processes has been regarded as a key tool toward the full implementation of process analytical technology. In this study, near-infrared (NIR) spectroscopy was examined for use as an in-line monitoring method of the paracetamol cooling crystallization process. The drug powder was dissolved in ethanol-based cosolvent at 60°C and was cooled by 1°C/min for crystallization. NIR spectra acquired by in-line measurement were interpreted by principal component analysis combined with off-line characterizations via X-ray diffraction, optical microscopy, and transmission electron microscopy. The whole crystallization process appeared to take place in three steps. A metastable form II polymorph of paracetamol was formed and transformed into the stable form I polymorph on the way to the growth of pure form I by cooling crystallization. These observations are consistent with a previous focused beam reflectance method-based study (Barthe et al., Cryst Growth Des 8:3316-3322, 2008).

Optimization of process parameters by Taguchi robust design method for the development of nano‐crystals of sirolimus using sonication based crystallization

“…12). This finding supports the findings Wang et al [52] for paracetamol where they have studied the impact of cooling on crystallization process.…”

Prediction of Polymorphic Transformations of Paracetamol in Solid Dispersions

“…The vibrational band due to the SOL in this region was flat indicating that it was not affecting the PMOL vibrational bands. It has been reported in previous NIR studies that the two polymorphs of PMOL (Form I and Form II) exhibit different vibrational band profiles. Similarly, from the data in Figure b, it can be seen that the second derivative NIR spectra showed a significant band shift, notably between 4900 and 4950 cm −1 , indicating that the polymorphic transformation of PMOL from its most stable Form I to the relatively less stable Form II takes place during the HME process at 120°C.…”

“…The vibrational band due to the SOL in this region was flat indicating that it was not affecting the PMOL vibrational bands. It has been reported in previous NIR studies 35,36 that the two polymorphs of PMOL (Form I and Form II) exhibit different vibrational band profiles. Similarly, from the data in Figure 5b, it can be seen that the second derivative NIR spectra showed a significant band shift, notably between 4900 and 4950 cm −1 , indicating that the polymorphic transformation of PMOL from its most stable Form I to the relatively less stable Form II takes place during the HME process at 120 • C. From the results obtained, it can be concluded that the band shifts between the NIR spectra of PMOL Form I and the extrudates (PMOL/SOL 40%-60%) support the findings from the VTXRPD data with regard to the predictions of the polymorphic transformation of PMOL (from its Form I to Form II) during HME.…”

Spectroscopic Techniques for Nondestructive Quality Inspection of Pharmaceutical Products: A Review

“…The PLS models showed accurate quantification with a high correlation coefficient (0.99) and lower standard errors (1.73%) for crystallinity determination. In addition, several works have been reported for the detection of crystallinity in various pharmaceutical substances such as polymorph A, glycine, paracetamol, miokamycin, and indomethacin using NIR spectroscopy Blanco et al, 2003;Bai et al, 2004;Otsuka et al, 2007;Wang et al, 2011;).…”