Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

Abstract

Objectives Solid-state transformations may occur during any stage of pharmaceutical processing and upon storage of a solid dosage form. Early detection and quantification of these transformations during the manufacture of solid dosage forms is important since the physical form of an active pharmaceutical ingredient can significantly influence its processing behaviour, including powder flow and compressibility, and biopharmaceutical properties such as solubility, dissolution rate and bioavailability. Key findings Vibrational spectroscopic techniques such as infrared, near-infrared, Raman and, most recently, terahertz pulsed spectroscopy have become popular for solidstate analysis since they are fast and non-destructive and allow solid-state changes to be probed at the molecular level. In particular, Raman and near-infrared spectroscopy, which require no sample preparation, are now commonly used coupled to fibreoptic probes and are able to characterise solid-state conversions in-line. Traditionally, uni-or bivariate approaches have been used to analyse spectroscopic data sets; however, recently the simultaneous detection of several solid-state forms has been increasingly performed using multivariate approaches where even overlapping spectral bands can be analysed. Summary This review discusses the applications of different vibrational spectroscopic techniques to detect and monitor solid-state transformations possible for crystalline polymorphs, hydrates and amorphous forms of pharmaceutical compounds. In this context, the theoretical basis of solid-state transformations and vibrational spectroscopy and common experimental approaches are described, including recent methods of data analysis.

Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation

“…FTIR was employed to investigate the potential interactions between L-leucine and azithromycin at the molecular level in the co-spray dried formulations (57). First, IR spectra of the Azithromycin-SD and the raw azithromycin (dihydrate) were compared (Fig.…”

The mechanism of porosity formation during solvent-mediated phase transformations

“…Since Cardew & Davey (1985) presented the first analysis of the kinetics of 'solvent-mediated phase transformations', it has become clear that such transformations play a key role in the mineralogical evolution of the Earth's crust, as well as in a wide range of industrial processes, including control of cement hydration (Tzschichholz et al 1996) and production of nano-structured devices (Sun & Xia 2004;Xia et al 2009). Pharmaceuticals and explosives often exhibit polymorphism, and they may transform from one crystal structure to another during storage and/or processing (Haleblian & McCrone 1969;Achuthan & Jose 1990;Rodriguez-Hornedo & Murphy 1999;Dharmayat et al 2008;Heinz et al 2009). This is important because the solubility, rate of dissolution, bioavailability, melting point and chemical stability of pharmaceuticals depend on the physical form and the crystal structure of the pharmaceutical, and because the processing behaviour, including compressibility and granular flow, varies from polymorph to polymorph.…”

Co-Amorphization of Ibuprofen by Paracetamol for Improved Processability, Solubility, and In vitro Dissolution

“…Such strong adhesive molecular interactions might have lead to band shifts in the IR spectra. 47,48 These shifts are also observed when a crystalline drug is converted into its amorphous form. 48 Here, molecular interaction between PA and IB were confirmed due to shift of phenolic C=O stretch, N-H stretch (amide) of PA and C=O stretch, O-H stretch (carboxylic acid) of IB.…”