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Rifaximin is a locally acting antibiotic practically insoluble in water. It presents several crystal phases characterized by different degrees of hydration. The aim of this work is to investigate the dissolution behaviour of rifaximin α, β, and amorphous forms in relation to their relative thermodynamic stability to contribute to clarifying possible solvent- or humidity-mediated conversion patterns. Kinetic and intrinsic solubility were investigated along with particle size distribution, specific surface area, and external morphology. The solution and moisture mediated conversion from metastable α and amorphous forms to stable β form were elucidated by coupling intrinsic dissolution test with chemometric analysis as well as by dynamic vapour sorption measurements. The dissolution behaviour of the α form stems mainly from the transition to β form that occurs upon exposition to relative humidity higher than 40%. The α form converted more rapidly than the amorphous form due to the smaller supersaturation ratio. It can be concluded that, due to its marked tendency to transform into β form, the dissolution test for the α form, even if conducted according to compendial procedures, needs to be accompanied by a panel of further tests that allow to uniquely identify the solid phase under investigation.

Rifaximin, a semisynthetic, rifamycin-based non-systemic antibiotic is used in the treatment of acute and chronic gastrointestinal disorders. The aim of this study was the elucidation of the molecular structure of the 802 Dalton impurity which was found in Rifaximin industrial batches and reported with an erroneous structure in European Pharmacopoeia 6.5 (2009) [7] monograph as Rifaximin Impurity H. This impurity was isolated from Rifaximin by preparative HPLC and purified by column chromatography. The molecular structure was evidenced by means of (1)H and (13)C NMR spectroscopy, mass spectrometry and FT-IR.

The enantiomers of iopanoic acid were purified by crystallization and characterized by optical rotation, DSC, IR spectra, X-ray powder diffraction, and chiral HPLC. (-R)-enantiomer: [α]20D = −6.1°, mp. = 165.4°C; (+S)-enantiomer: [α]20D = + 6.2°, mp. = 165.6°C. The IR spectra and X-ray patterns are fingerprints. Chiral HPLC (isocratic method, mobile phase: ethanol/n-hexane, 2/98 with 0.5% acetic acid) gave a resolution = 0.98 and a 99.6% recovery. From X-ray and thermal analyses the racemate Form I, mp. = 153.8°C, resulted to be a racemic compound. The binary phase diagram between the enantiomers and the racemic compound was constructed from the phase transition temp. obtained by DSC heating curves of appropriate mixtures. At a given enantiomer ratio (71/29) a eutectic compound, mp. = 144.7°C, is formed. In the range 88–100% a solid solution between the components is observed. Weitere Charakterisierung der festen Formen der Iopansaure und ihrer Enantiomeren Die Enantiomeren der Iopansaure wurden durch Umkristallisieren gereinigt und durch optische Rotation, Differentialscanningkalorimetrie, IR Spektrum, Rontgenpulverdiffraktion und chirale HPLC charakterisiert. (-R)-Enantiomer: [α]20D = −6.1°, Schmp. = 165.4°C; (+S)-Enantiomer: [α]20D = +6.2°, Schmp. = 165.5°C. Das IR-Spektrum und das Rontgenmuster sind Fingerabdrucke. Chirale Hochdruckflussigkeitschromatographie (isokratisch; mobile Phase: Ethanol/n-Hexan, 2/98 mit 0.5% Essigsaure) gab eine Trennung (0.98) mit 99.6% Ausbeute. Rontgenspektrum und thermischen Analyse bewiesen, daβ die Form I mit Schmp. 153.8°C ein Racemat ist. Das Zweiphasendiagramm zwischen den Enantiomeren und dem Racemat wurde aus den Phasenubergangstemperaturen konstruiert, die durch DSC Erhitzungkurven von geeigneten Mischungen erhalten wurden. Beim Isomerengemisch 71/29 liegt ein Eutektikum Schmp. 144.7°C. Im Bereich 88-100% liegen die Komponenten als feste Losung vor.

The determination of enantiomeric purity by Differential Scanning Calorimetry (DSC) was applied in the case of (1R,2R)-2-amino-1-(4-nitrophenyl)-1,3-propanediol. In the range of enantiomeric excess (greater than 95%), the direct and indirect methods gave identical results. Calorimetrische Bestimmung der Enantiomerenreinheit von (1R,2R)-2-Amino-1-(4-nitrophenyl)-1,3-propandiol Die Enantiomerenreinheit von (1R,2R)-2-Amino-1-(4-nitrophenyl)-1,3-propandiol wurde mit der Differential Scanning Calorimetry (DSC) bestimmt. Bei einem Enantiomerenuberschus von > 95% lieferten die direkten und indirekten Methoden die gleichen Ergebnisse.