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Dive into the research topics where Cyrille Andrès is active.

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Featured researches published by Cyrille Andrès.


International Journal of Pharmaceutics | 2002

Dry powder inhaler: influence of humidity on topology and adhesion studied by AFM

V Bérard; E Lesniewska; Cyrille Andrès; D Pertuy; C Laroche; Y. Pourcelot

In the dry powder inhalers (DPIs), the adhesion results of the interactions between the active substance and the excipient. The carrier and the micronized drug particle morphologies are believed to affect the delivery of the drug. In this work, the couple studied was the lactose monohydrate and micronized zanamivir, used for the treatment of influenza. In a first approach, observations by scanning electron microscopy (SEM) have shown that the relative humidity (RH) greatly influenced the zanamivir amount fixed on the lactose monohydrate surface. This paper deals with the direct measurement in controlled atmosphere by atomic force microscopy (AFM) of the forces and the interaction ranges between a zanamivir probe and a lactose substrate. Selected zanamivir crystals were attached to the standard AFM probe. Different RH have been used in order to determine influent parameters permitting to identify the nature of adhesion forces between them. This study demonstrated that the increase of RH modified progressively the surface topology of the two components and increased the adhesion force.


International Journal of Pharmaceutics | 2002

Affinity scale between a carrier and a drug in DPI studied by atomic force microscopy

V Bérard; E Lesniewska; Cyrille Andrès; D Pertuy; C Laroche; Y. Pourcelot

The dry powder inhalers (DPIs) consist, in the most cases, of ordered mixture where the particles adhesion results of interactions between the drug and the carrier. Generally, one step of production process is the micronization of the drug particles in order to reduce the size for ordered mixing optimization. But this operation is known to partially create an amorphous surface. In this case, surrounding storage conditions, like relative humidity (RH), are able to modify the percentage of amorphous drug surface. The aim of this study was to investigate surface reactivity, surface energy and direct force measurements by atomic force microscopy (AFM) between lactose (carrier) and zanamivir (drug) crystals references in various conditions of RH. Secondly, an amorphization of the drug surface was induced by humidity relative treatment in order to evaluate the consequences of the transition from crystal to amorphous phase. The study demonstrated that the amorphization of drug surface induces an increase of drug affinity with the carrier surface. Ex situ and in situ amorphization of zanamivir tend to reach the affinity measured between raw materials: carrier and micronized drug particles. AFM allowed adhesion force discrimination between the different forms of the drug particles and demonstrated the potential for investigating adhesion properties in DPI formulation.


International Journal of Pharmaceutics | 2001

The spray drying of acetazolamide as method to modify crystal properties and to improve compression behaviour

Piera Di Martino; Mara Scoppa; E. Joiris; Giovanni Filippo Palmieri; Cyrille Andrès; Y. Pourcelot; Sante Martelli

Acetazolamide shows a very poor compression ability and tablets must usually be produced through a wet granulation process. However, the possibility to obtain pure acetazolamide for direct compression could be interesting for industrial application. With the scope to obtain a material for direct compression, three different crystallisation methods were chosen, with respect to acetazolamide solvent solubility. (a) Acetazolamide was dissolved in an ammonia solution and then spray dried. It was possible to characterise the spherical particles as a mixture of two polymorphic forms, I and II by Powder X-ray diffraction study. (b) Pure form I was obtained by slowly cooling to room temperature a boiling water solution. (c) Pure form II, the marketed form, was obtained by neutralisation of an ammonia solution. Their compression behaviour was investigated firstly by a rotary press. Whilst pure polymorphic forms I and II could not be compressed, the spray dried particles showed very good compression properties. In fact, tablets were obtained only by spray dried particles, which show very good properties under compression and the absence of capping tendency. On the other hand, it was impossible to obtain tablets from polymorphic forms I and II, whatever compression pressures were used. In order to explain their densification mechanism, a single-punch tablet machine, equipped for the measurement of the upper punch displacement in the die, was used. From calculated Heckels parameters, it was demonstrated that the spray dried material shows a greater particle rearrangement in the initial stage of compression due to its spherical habit and minor wrinkledness of particle surface. The crystalline structure due to the presence of polymorphic forms I and II concur to lowering the intrinsic elasticity of the material. This fact avoids the risk of the rupturing the interpaticulate bonds, which are formed during the compression, concurring to the consolidation of the tablet.


International Journal of Pharmaceutics | 2003

Comparative study of the lubricant performance of Compritol 888 ATO either used by blending or by hot melt coating.

V. Jannin; V Bérard; A. N’Diaye; Cyrille Andrès; Y. Pourcelot

Compritol 888 ATO is used as a lubricant in oral solid dosage formulations. It can also be used as a hot melt coating agent sprayed onto a powder. In this study, we compare the lubricant performance of Compritol 888 ATO either used by classical blending or by hot melt coating onto Lactopress by compression tests. In physical mix, the Compritol concentration does not affect the compressibility. The same compressibility is obtained with lactose coated by 0.5 or 1% of Compritol, but a higher compressibility can be observed with 2 and 3%. Cohesiveness of lactose depends on the process: hot melt coating induces a decrease of tablet tensile strength. In terms of forces transmission during compression phase and axial ejection pressures, Compritol used by hot melt coating allows for a concentration of 0.5% to directly obtain the lubricant performance of 3% of Compritol used by blending. These results suggest that the hot melt coating process induces an homogeneous repartition of the lubricant on the lactose surface, contrary to classical blending procedure. Thus, lubrication by hot melt coating seems to be a very efficient procedure. It could be used specifically for large surface area particulate systems producing a lot of friction.


International Journal of Pharmaceutics | 2001

On the difficulty of assessing the specific surface area of magnesium stearate

Cyrille Andrès; Pierre Bracconi; Y. Pourcelot

The water content of as-received commercial magnesium stearate batches from animal and vegetable sources have been modified by ageing in humid air at room temperature or by vacuum treatment. The complete adsorption-desorption isotherms of nitrogen and krypton vapours by samples of these as received and modified materials have been measured at liquid nitrogen temperature after standardised vacuum degassing. They are greatly affected by the initial water content of the material. In particular: (a) the BET surface area values computed from the adsorption branch vary widely and is increasing with increasing water content; (b) anomalous hysteresis of varying amplitude is observed in all cases except adsorption of krypton on the material with the lowest water content; (c) the hysteresis loops extend down to very low desorption pressure values and cannot be accounted for by capillary condensation. Lastly, the surface area value of a given material computed from nitrogen and krypton adsorption may differ by a factor as high as six. Accordingly, the very significance of BET surface area values obtained from routine adsorption experiments should be regarded as questionable, at least until the mechanisms of adsorption are fully clarified.


International Journal of Pharmaceutics | 2003

Comparative study of the lubricant performance of Compritol HD5 ATO and Compritol 888 ATO: effect of polyethylene glycol behenate on lubricant capacity.

A. N’Diaye; V. Jannin; V Bérard; Cyrille Andrès; Y. Pourcelot

The aim of this paper is to study the lubricant capacity of Compritol HD5 ATO, a glyceryl and polyethylene glycol dibehenate, obtained by atomization. This material is compared to Compritol 888 ATO, constituted only by glyceryl dibehenate. First, this study verifies that Compritol HD5 ATO and Compritol 888 ATO present the same granular characteristics and that their mixes with Lactopress present no structural differences. Secondly, in term of compressibility and cohesiveness, the use of Compritol 888 ATO or Compritol HD5 ATO with Lactopress does not involve any significant modification. Finally, the minor difference of lubricant capacity between Compritol HD5 ATO and Compritol 888 ATO has no consequence in compression practice. The presence of polyethylene glycol behenate does not decrease the glyceryl dibehenate compression functionality. This study concludes that Compritol HD5 ATO could be a very interesting excipient because it associates the glyceryl dibehenate lubricant capacity with the polyethylene glycol behenate-specific capacity in terms of dissolution enhancement.


International Journal of Pharmaceutics | 2003

Structural properties of magnesium stearate pseudopolymorphs: effect of temperature.

Pierre Bracconi; Cyrille Andrès; Augustin Ndiaye

A thorough review of the relevant literature reveals that the interaction between water vapour and magnesium stearate, in contrast to many other metal soaps, is not properly understood. The structural modifications associated with the up-take or loss of water of vegetable-derived commercial magnesium stearate powders exposed to humid air or vacuum at room temperature are investigated using standard powder X-ray diffractometry. It is found that in such conditions magnesium stearate reacts reversibly with the vapour phase with structural consequences very similar to the high temperature transition between the crystalline and rotator phases of other anhydrous metal soaps. When temperature is increased under dry nitrogen the diffraction band characteristic of the rotator phase shifts towards higher angle values and the corresponding lattice spacing increases at the rate of 6.9x10(-4)C(-1). Melting takes place gradually above 100 degrees C as revealed by the collapse of the diffraction band and the growth of the broader diffusion band characteristic of the liquid state. Full clarification of the structure of the hydrated and dried phases proves impossible based on powder diffraction spectra obtained with conventional high resolution X-ray diffraction equipment.


International Journal of Pharmaceutics | 1996

Particle-size distribution of a powder : comparison of three analytical techniques

Cyrille Andrès; P. Réginault; M.H. Rochat; B. Chaillot; Y. Pourcelot

The purpose of this study is to compare two diffraction techniques (particle in air, PIA and particle in liquid, PIL) to an image analysis (IA), on spherical standard powders, applied to two different samples as a matter of particle size distribution (P52 and P260). We show by a direct qualitative comparison of the distribution curves that PIA and PIL give the same results in all cases, and that IA and diffraction methods can be considered as similar, excepted for P52 number analysis. The statistical layout demonstrates that the two diffraction methods give very close results. IA and laser methods provide us with different results except in the case of P260 in volume. In IA, there is a critical number of particles to be counted; this number is influenced by the width of the distribution. PIA and PIL are also influenced by the breadth of the distribution, depending on the principle of working. We show the importance of choice and complementarity of these techniques to measure the distribution size.


International Journal of Pharmaceutics | 1998

Assessing the particle size of a broadly dispersed powder by complementary techniques

Cyrille Andrès; Pierre Bracconi; P. Réginault; P Blouquin; M.H. Rochat; Y. Pourcelot

The experimental determination of reliable particle size distribution curves and statistical parameters of broad distributions is known to be a difficult task. This problem is addressed here in an attempt to characterize the granularity of three distinct batches of a pharmaceutical powder (fenofibrate from Fournier Laboratories). The methodology consists in comparing the results, expressed in terms of surface based mean diameter, as obtained by three complementary techniques, namely optical microscopy image analysis, laser light low angle diffraction and surface area measurement by krypton physisorption. These techniques are applied in parallel to the material of interest and to a certified reference material, a nearly spherical and narrowly distributed glass powder.


Journal of Pharmaceutical Sciences | 2010

New binary solid dispersion of indomethacin with surfactant polymer: From physical characterization to in vitro dissolution enhancement

Aurélien Sivert; Véronique Bérard; Cyrille Andrès

This article investigated preparation of solid dispersions containing a poor water-soluble drug, indomethacin (IND), and a new surfactant polymer, polyoxyethylene 32 distearate (POED). Solid dispersions were prepared by the melting method and characterized by DSC, hot-stage microscopy (HSM), X-ray diffraction (XRD) and scanning electron microscopy (SEM). DSC and HSM analyses performed on IND/POED physical mixtures indicated that IND could dissolve in liquid POED. The materials showed complete miscibility at liquid state. Combination of DSC, XRD, and SEM revealed that these materials had limited miscibility at the solid state. Up to 20% w/w IND in POED, we did not detect significant modification of physical properties of the polymer. It supports the formation of a solid solution of IND in solid POED. Above 20% w/w, the solid dispersions presented particular behavior upon heating (recrystallization of IND) and at the solid state (presence of some IND crystallites). Under 3-month storage at 25 degrees C/53% RH, the solid dispersions demonstrated a good stability of the samples. Finally, in vitro dissolution studies showed that IND release was greatly improved (5.5-12 times as fast) by formation of solid dispersion. This enhancement was principally attributed to the high dispersion of IND in POED and to the polymer surfactant properties.

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V Bérard

University of Burgundy

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B. Chaillot

University of Burgundy

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M.H. Rochat

University of Burgundy

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