Quantification of drug amorphous fraction by DSC

The processes of production of drugs and dosage forms in the solid state often cause unwanted transformation of portions of the substances into amorphous state, with significant changes of properties such as stability and bio-availability. When this amorphous fraction is of the order of a few percent, it usually goes unnoticed, but it should be accurately determined within a quality control system. In this work, we consider a model drug, perphenazine, where partial amorphisation may be induced by standard mechanical treatments. We show that Differential Scanning Calorimetry (DSC) leads to consistent estimations of the amorphous fractions induced by the treatment. Furthermore, DSC also yields the expected amounts of amorphous perphenazine when analysing known mixtures of perfectly crystalline samples (untreated) and partially amorphous samples (treated). We show that even amorphous fractions of the order of 1% are accurately estimated by our method.     

Evolution strategy optimization for adiabatic pulses in MRI.

We propose a new type of adiabatic pulses for uniform inversion of the magnetization in magnetic resonance imaging. We produced these pulses with an evolution strategy optimization, by which the search of the "best solution" has been made more efficient than by deterministic algorithms. The pulse parametrization takes into account an "offset-independent adiabaticity condition," which guarantees insensitivity to RF inhomogeneities. The RF pulse power (both peak and mean) contributes to the cost to be minimized, as well as the error function does: in this way we obtain solutions that require lower energy than the well-known hyperbolic-secant pulse, with no loss of quality in the response profile.     

Drug-excipient compatibility studies by physico-chemical techniques; The case of Indomethacin

This work exemplifies a general method of studying the drug excipient interactions, with the aim of predicting rapidly and inexpensively the long term stability of their mixtures. We study the physico-chemical properties of a drug (indomethacin) in the solid state and in different combinations with several excipients (PVP=polyvinylpyrrolidone, MGST=magnesium stearate, Avicel^©). We compare the properties of pure compounds (untreated, or moisture/temperature conditioned) with those of binary mixtures drug:excipient which underwent the same treatment. The purpose is to find indications of interactions within the mixtures, which means a potential incompatibility of the excipient. Both morphological and thermal properties are sensitive to interactions which leave mostly unmodified the IR spectra and the X-rays patterns. In particular, we find that indomethacin does interact with PVP and MGST, but is certainly compatible with Avicel^©.     

Drug-excipient compatibility studies by physico-chemical techniques; The case of Atenolol

We apply a range of techniques (thermal methods, microscopy, X-ray diffraction, IR spectroscopy) to characterize a drug (atenolol), several excipients (PVP=polyvinylpyrrolidone, MGST=magnesium stearate, Avicel©) and drug-excipients mixtures either as prepared, annealed, and exposed to moisture. We compare the data of the mixtures with those computed from a weighted average of similarly treated pure compounds to find evidence of drug properties modified by the interaction with the excipient. We find that thermal response is by far the most sensitive indicator of interaction while IR is the least sensitive one. Avicel© has essentially no interaction with atenolol, while MGST modifies significantly only the thermal response of the drug in the MGST-rich mixtures. PVP interacts strongly with atenolol, and this interaction appears to be mediated by the substantial amount of hydration water the excipient brings in its mixtures with a water-free drug.     

Physico-chemical characterization of anhydrous <Emphasis Type="Italic">D</Emphasis>-mannitol

In this work the solid-state characterization of anhydrous D-mannitol has been performed: α and β modifications can be distinguished only by XRPD and FTIR as they show melting temperature and enthalpy that are the same within the standard deviation. The understanding of the thermal behaviour of the δ form (obtained by re-crystallization in acetone) has required XRPD experiments performed at variable temperature. This form during heating undergoes a solid phase transition to α modification. By cooling a melted sample, under a wide range of experimental conditions, a very fast crystallization occurs. Independently of the starting crystal form (β or δ form), the re-crystallization of D-mannitol from melt always leads to α form.     

Evolution Strategy Optimization for Selective Pulses in NMR

We present a first set of improved selective pulses, obtained with a numerical technique similar to the one proposed by Geen and Freeman. The novelty is essentially a robust and efficient “evolution strategy” which consistently leads, in a matter of minutes, to “solutions” better than those published so far. The other two ingredients are a “cost function,” which includes contributions from peak and average radiofrequency power, and some understanding of the peculiar requirements of each type of pulse. For example, good solutions for self-refocusing pulses and “negative phase excitation pulses” (which yield a maximum signal well after the end of the pulse) are found, as may have been predicted, among amplitude modulated pulses with 270° tip angles. Emphasis is given to the search for solutions with low RF power for selective excitation, saturation, and inversion pulses. Experimental verification of accuracy and power requirements of the pulses has been performed with a 4.7 T Sisco imager.     

Study of the copper effect in iron-gall inks after artificial ageing

Iron-gall inks consist of a mixture of vitriols (sulphates of certain metals), gall nut extracts and arabic gum. The association of the iron(II) sulphate present in vitriols, and the gallic acids present in the gall nut extracts induces, after exposure to oxygen, the formation of dark coloured compounds of ink. In addition to iron, this kind of inks contains other metals, such as copper, zinc, and nickel. Among them, copper could be considered the most important because, owing to its catalytic ability, it can be involved in the processes concerning formation and stability of iron complexes, which are responsible for the ink dark colour. For this purpose, four different iron-gall inks containing increasing amounts of copper sulphate were prepared according to a traditional receipt and applied on paper supports. The ink-stained paper specimens were subjected to an intense analytical program to investigate their chemical and physical modifications after artificial ageing (both temperature/humidity and ultraviolet light ageing). The role of copper in the iron-gall inks was evaluated using optical microscopy, colorimetric measurements, X-ray fluorescence (XRF), X-ray diffraction analysis (XRD), scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM–EDX) and Fourier transform infrared spectroscopy (FTIR). For the evaluation of the oxidation state of iron and copper, X-ray absorption spectroscopy (XANES) was used. All results indicate that the presence of copper in iron-gall ink causes colour variation, affects the migratory behaviour of iron in the paper, increases the formation of secondary products particularly when ageing process based on temperature/humidity variations is considered.     

Solvent suppression by post-processing

A post-processing solvent-suppression technique is illustrated which eliminates the dispersive component by symmetrizing the time-data, and the absorption component by filtering in the frequency domain.