0000000000213010
AUTHOR
C. Andrès
Structural properties of magnesium stearate pseudopolymorphs: effect of temperature.
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 i…
On the difficulty of assessing the specific surface area of magnesium stearate
Abstract 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…
LIM Kinases: new anticancer therapeutic targets
International audience
Comparative study of the lubricant performance of Compritol® HD5 ATO and Compritol® 888 ATO: effect of polyethylene glycol behenate on lubricant capacity
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 n…
Thermal analyses of commercial magnesium stearate pseudopolymorphs
Abstract Two commercial magnesium stearate powders in two well-characterised structural states are investigated using DSC and coupled TGA–DTA under dry nitrogen flow. They consist of either a mixture of crystalline hydrates or a poorly crystallised so-called anhydrate. Following the degassing of unbound water, 1 or 3 weight-loss peaks are observed below about 100 °C, each associated with one heat loss peak at the same temperature. The present results and a review of graphical data from literature show that the so-called anhydrate always contains a significant amount of water. At the beginning of the dehydration process, the heat loss is the same as the standard heat of vaporisation of water…
Comparative study of the lubricant performance of Compritol 888 ATO either used by blending or by hot melt coating.
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 compres…
New binary solid dispersion of indomethacin with surfactant polymer: From physical characterization to in vitro dissolution enhancement
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 modifica…
Study of Morphology of Reactive Dissolution Interface Using Fractal Geometry
J. Pharm. Sci. ISI Document Delivery No.: VF662 Times Cited: 7 Cited Reference Count: 15 Tromelin, A Gnanou, JC Andres, C Pourcelot, Y Chaillot, B; International audience; The determination of reactive fractal dimension was carried out using two forms of the Noyes-Whitney equation, -dQ/dt = K(Q/Q(0))(DR/3) and -d Q/dt = K' R(DR-3) using the Richardson plot on the basis of previous data obtained by dissolution of an orthoboric acid powder. The correlation of the results provided by the two ways of calculation allows proposal of the hypothesis that dissolution begins on a specific population of reactive sites and probably promotes the formation of microporous volumes or cracks.
Assessing the particle size of a broadly dispersed powder by complementary techniques
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…
Influence of the parameters molecular structure and granularity on the compactibility of a powder
Drug Dev. Ind. Pharm. ISI Document Delivery No.: RP128 Times Cited: 3 Cited Reference Count: 14 Andres, c ndiaye, a thomas, c tromelin, a chaillot, b pourcelot, y; International audience; The aim of this study was to determine whether it is possible to obtain better characterization of materials in order to find out if these one are suitable in Quality Assurance for direct tableting. We tried to show that a methodological approach combining chemical, physical and technological aspects could control the direct compression process. We chose orthoboric acid as a study model for the direct compression. From a chemical point of view, our findings show only one crystalline molecular structure (RX…
Preformulation: Effect of Moisture Content on Microcrystalline Cellulose (Avicel PH-302) and Its Consequences on Packing Performances
This study evaluates the influence of moisture content on the packing performances of a new grade of microcrystalline cellulose (MCC) (Avicel PH-302) either by classical method or by an unconventional compression technique (constant volume reduction of powder bed). An increase in moisture content decreases the apparent density of the powder bed, resulting from interparticulate friction enhancement. This modification of apparent density seems to be the main effect caused by the presence of humidity, which explains the variations of compression properties, like an increase of powder plasticity generally observed in the experimental conditions.
Affinity scale between a carrier and a drug in DPI studied by atomic force microscopy.
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 (dr…
Functional characterisation of powders consisting of mixtures of glyceryl behenate and a non-ionic surfactant applied by hot-melt coating: lubricant performance
Solid-phase lubricants are routinely used in tablet manufacturing to reduce friction during the densification and ejection phases. However, two main challenges are commonly observed: a) poor blending of the lubricant with the other components; b) increased hydrophobicity of the mix. Hot-melt coating, wherein the substrate is coated with a composite lubricant consisting of glyceryl behenate and a non-ionic surfactant (polyethylene glycol behenate), offers a solution to these challenges. Comparative studies were undertaken using the composite lubricant in a hot-melt coating process and in a ‘standard’ physical blending method. This study shows that the addition of a surfactant to glyceryl beh…
Relationship between particle size and dissolution rate of bulk powders and sieving characterized fractions of two qualities of orthoboric acid
Drug Dev. Ind. Pharm. ISI Document Delivery No.: VN279 Times Cited: 1 Cited Reference Count: 22 Tromelin, A Habillon, S Andres, C Pourcelot, Y Chaillot, B; International audience; We have carried out a study of the particle size distribution and aqueous dissolution rate of two commercially available qualities of orthoboric acid, labeled ''crystal'' (ABC) and ''powder'' (ABP). In a previous work, we have shown that the two commercial qualities of orthoboric acid chosen as model compound (''powder'' and ''crystal'') are related to the same crystal network in spite of their different names. However, these two qualities have very different size particle distributions, as previously determined b…