Insights into phase stability of anhydrous/hydrate systems: a Raman‐based methodology

Abstract

FT-Raman spectroscopy turns out to be a powerful technique to evaluate the amount of polymorphic and pseudopolymorphic forms in crystalline samples -which is particularly relevant in pharmaceutical sciences. This paper presents a methodology that allows successful quantitative evaluation of the solid-state hydration and dehydration processes, using FT-Raman spectroscopy. All the steps required for a reliable evaluation of the hydration/dehydration process are illustrated for the caffeine system, a particularly challenging system presenting limited spectral differences between the pseudopolymorphs. The hydration process of caffeine was found to occur in a single-step process with a half-life time of ca 13 h, while the dehydration occurs through a two-step mechanism. The critical relative humidity was found to be at ca 81 and 42% for anhydrous and hydrate caffeine forms, respectively.

Recent advances in linear and nonlinear Raman spectroscopy. Part V

“…FT‐Raman spectroscopy is a powerful technique to evaluate the amount of polymorphic and pseudopolymorphic forms in crystalline samples – which is particularly relevant in pharmaceutical sciences. In a paper by Nolasco et al ., a methodology is presented that allows successful quantitative evaluation of solid‐state hydration and dehydration processes by using FT‐Raman spectroscopy . The use of Raman spectroscopy for the qualitative and quantitative analysis of dilute aqueous solutions is of interest to the biopharmaceutical manufacturing sector; however, the inherent weakness of the Raman effect, coupled with spectral variability due to spurious signals from sample holders, can produce significant problems for chemometric‐based high‐throughput assays.…”

On the Relevance of Considering the Intermolecular Interactions on the Prediction of the Vibrational Spectra of Isopropylamine

“…This approach assumes that the effects of the individual intermolecular interactions, in which a given molecular entity is involved in, are pairwise additive. Application of the method has been used with success in the assignment of the vibrational spectra of several solid pharmaceutical drugs known to present polymorphic forms [48][49][50][51]. However, that accuracy evaluation was conditioned by the fact that, according to the X-ray data available for those drugs, none of the systems presented a molecular group involved in multiple hydrogen bonds.…”

Solvomorphs of tyraminium 5,5-diethylbarbiturate: a rare example of the barbiturateR33(12) hydrogen-bond motif and a crystal structure withZ′ = 4

“…Interest in the development of novel polymorphic and solvomorphic forms has increased rapidly in the last two decades, especially in the field of pharmaceuticals and materials sciences (Vishweshwar et al, 2006;Powell et al, 2015;Almarsson & Zaworotko, 2004). The study of pseudopolymorphism (or solvomorphism) has focused industrial attention as the addition of solvent molecules to a crystal structure affects the macroscopic properties of a crystal, such as hardness, hygroscopicity and melting point, and also the pharmacokinetic and pharmacodynamic properties of a drug (Karpinski, 2006;Nolasco et al, 2010;Gutierrez et al, 2011;Kato et al, 2008;Bechtloff et al, 2001;Singhal & Curatolo, 2004;Rodríguez-Spong et al, 2004). The scientific research has focused on finding all possible polymorphic/solvomorphic forms of a given system and on improving the physical and chemical properties (e.g.…”