French Roadmap for complex Systems 2008-2009

This second issue of the French Complex Systems Roadmap is the outcome of the Entretiens de Cargese 2008, an interdisciplinary brainstorming session organized over one week in 2008, jointly by RNSC, ISC-PIF and IXXI. It capitalizes on the first roadmap and gathers contributions of more than 70 scientists from major French institutions. The aim of this roadmap is to foster the coordination of the complex systems community on focused topics and questions, as well as to present contributions and challenges in the complex systems sciences and complexity science to the public, political and industrial spheres

Novel gamma crystalline form of perindopril tert-butylamine salt, preparation method, and pharmaceutical compositions containing same.

The invention concerns a η crystalline form of a compound of formula (I) characterised by its X-ray diffraction pattern on powder. The invention is applicable to medicines

Novel "beta" crystalline form of perindopril tert-butylamine salt, preparation method, and pharmaceutical compositions containing same

The invention concerns the β crystalline form of the compound of formula (I), characterised by its X-ray diffraction pattern on powder. The invention is useful for preparing medicine

Detection of low-dose of piroxicam polymorphs in pharmaceutical tablets by surface-enhanced Raman chemical imaging and multivariate analysis

In the pharmaceutical industry, the detection and the identification of polymorphic forms of an active pharmaceutical ingredient (API) is an important concern during the drug development and the manufacturing process. The necessity to detect polymorphic forms especially at low concentrations is an area of particular interest in pharmaceutical applications due the difference of physico-chemical properties exhibited by the polymorphs. The polymorphic behavior of drugs can affect the therapeutic efficacy of the drug substance and can also have an impact from an intellectual property (IP) standpoint. Indeed, much effort are expended by the regulatory authorities to determine if the polymorph present in the final product is covered by a patent for IP rights aspects. Various analytical techniques can be used for polymorph detection and characterization such as X-ray powder diffraction (XRPD), solid-state nuclear magnetic resonance spectroscopy (ssNMR) and vibrational spectroscopy. Despite low sensitivity and long image acquisition times, Raman microscopy is well suited to the analysis of polymorphic forms since it enables the acquisition of spectral and spatial information at the same time. This technique can be combined with surface-enhanced Raman scattering (SERS), resulting in surface-enhanced Raman chemical imaging (SER-CI). SER-CI is a promising tool for the detection and the visualization of low-dose compounds or impurities in tablets taking account of the high sensitivity of this technique. Consequently, we firstly focused on the development of a reproducible spray-coating method to control the deposition of SERS nanoparticles on pharmaceutical samples in order to fully exploit the potential of SER-CI. Besides, this spraying technique, coupled with SER-CI, was applied to model tablets consisting of one excipient and a 10% (w/w) API concentration. Piroxicam, a non-steroidal anti-inflammatory drug which presents three polymorphic forms was used as a model API. The model formulation was a binary mixture of the form β and the form α2 polymorphs of piroxicam. Using SER-CI and multivariate analysis, it was possible to detect the β form polymorph in these model tablets below 1% (w/w) while reducing the image acquisition time. To conclude, the combination of the spray-coating method and SER-CI enabled the detection of low-dose of piroxicam polymorphs in model pharmaceutical formulations. This approach can serve as a potential way for the development of methods validation for semi-quantitative and quantitative analyse

Application of surface-enhanced Raman chemical imaging (SER-CI) to quantification in pharmaceutical tablets

Since its discovery, the application of Surface-Enhanced Raman Spectroscopy (SERS) has extended to various areas, including the pharmaceutical field, facing up challenges in the SERS substrate and sample preparation. This paper will present how beneficially SERS can be applied to the quantification of low-dose compounds in pharmaceutical tablets, focusing on the determination of 4-aminophenol, a toxic impurity, in acetaminophen tablets

Chemical imaging: An essential mechanism to assess pharmaceutical (Part 1)

This article is intended to make known the contribution of chemical imaging to the professions of pharmacy, biopharmacy or cosmetics, whether in the research phase of an active substance (experimental pharmacology), in the development of a formulation or in quality control, or even as an additional tool for solving quality-related problems in industrial production. It has been written for an uninitiated audience to provide the latter with the methodological basics and key points that will help it better understand the concept. Chemical imaging is currently the only tool that allows us to visualise, without labelling, the spatial distribution of chemical (or biochemical) species within a sample. This is an essential added value compared to optical microscopy.his article is intended to make known the contribution of chemical imaging to the professions of pharmacy, biopharmacy or cosmetics, whether in the research phase of an active substance (experimental pharmacology), in the development of a formulation or in quality control, or even as an additional tool for solving quality-related problems in industrial production. It has been written for an uninitiated audience to provide the latter with the methodological basics and key points that will help it better understand the concept. Chemical imaging is currently the only tool that allows us to visualise, without labelling, the spatial distribution of chemical (or biochemical) species within a sample. This is an essential added value compared to optical microscopy

Towards a spray-coating method for the detection of low-dose compounds in pharmaceutical tablets using surface-enhanced Raman chemical imaging (SER-CI)

Surface-enhanced Raman chemical imaging (SER-CI) is a highly sensitive analytical tool recently used in the pharmaceutical field owing to the possibility to obtain high sensitivity along with spatial information. However, the covering method of the pharmaceutical samples such as tablets with metallic nanoparticles is a major issue for SER-CI analyses due to the difficulty to obtain a homogeneous covering of tablet surface with the SERS substrates. In this context, a spray-coating method was proposed in order to fully exploit the potential of SER-CI. A homemade apparatus has been developed from an electrospray ionization (ESI) probe in order to cover the pharmaceutical tablets with the colloidal suspension in a homogeneous way. The silver substrate was pulled through the airbrush by a syringe pump which was then nebulized into small droplets due to the contact of the solution with the gas flow turbulence. A robust optimization of the process was carried out by adjusting experimental parameters such as the liquid flow rate and the spraying time. Besides, the performances of this spraying technique were compared with two others covering methods found in the literature which are drop casting and absorption coating. A homogeneity study, conducted by SER-CI and matrix assisted laser desorption/ ionization mass spectrometry imaging (MALDI-MSI) applied to the different covering techniques was performed. The influence of the metallic nanoparticles deposit on soluble compounds was also investigated in order to highlight the advantages of using this new spray coating approach

Critical review of surface-enhanced Raman spectroscopy applications in the pharmaceutical field

Surface-enhanced Raman spectroscopy (SERS) is a sensitive analytical tool used in the pharmaceutical field in recent years. SERS keeps all the advantages of classical Raman spectroscopy while being is more sensitive allowing its use for the detection and the quantification of low-dose substances contained in pharmaceutical samples. However, the analytical performance of SERS is limited due to the difficulty to implement a quantitative methodology correctly validated. Nevertheless, some studies reported the development of SERS quantitative methods especially in pharmaceutical approaches. In this context, this review presents the main concepts of the SERS technique. The different steps that need to be applied to develop a SERS quantitative method are also deeply described. The last part of the present manuscript gives a critical overview of the different SERS pharmaceutical applications that were developed for a non-exhaustive list of pharmaceutical compounds with the aim to highlights the validation criteria for each application