Claire Bordes

Determination of poly(ɛ-caprolactone) solubility parameters: Application to solvent substitution in a microencapsulation process

The evolution of regulation on chemical substances (i.e. REACH regulation) calls for the progressive substitution of toxic chemicals in formulations when suitable alternatives have been identified. In this context, the method of Hansen solubility parameters was applied to identify an alternative solvent less toxic than methylene chloride used in a microencapsulation process. During the process based on a multiple emulsion (W/O/W) with solvent evaporation/extraction method, the solvent has to dissolve a polymer, poly(epsilon-caprolactone) (PCL), which forms a polymeric matrix encapsulating or entrapping a therapeutic protein as the solvent is extracted. Therefore the three partial solubility parameters of PCL have been determined by a group contribution method, swelling experiments and turbidimetric titration. The results obtained allowed us to find a solvent, anisole, able to solubilize PCL and to form a multiple emulsion with aqueous solutions. A feasibility test was conducted under standard operating conditions and allowed the production of PCL microspheres.

Spray-drying Nanocapsules in Presence of Colloidal Silica as Drying Auxiliary Agent: Formulation and Process Variables Optimization Using Experimental Designs

PurposeSpray-drying process was used for the development of dried polymeric nanocapsules. The purpose of this research was to investigate the effects of formulation and process variables on the resulting powder characteristics in order to optimize them.Materials and MethodsExperimental designs were used in order to estimate the influence of formulation parameters (nanocapsules and silica concentrations) and process variables (inlet temperature, spray-flow air, feed flow rate and drying air flow rate) on spray-dried nanocapsules when using silica as drying auxiliary agent. The interactions among the formulation parameters and process variables were also studied. Responses analyzed for computing these effects and interactions were outlet temperature, moisture content, operation yield, particles size, and particulate density. Additional qualitative responses (particles morphology, powder behavior) were also considered.ResultsNanocapsules and silica concentrations were the main factors influencing the yield, particulate density and particle size. In addition, they were concerned for the only significant interactions occurring among two different variables. None of the studied variables had major effect on the moisture content while the interaction between nanocapsules and silica in the feed was of first interest and determinant for both the qualitative and quantitative responses. The particles morphology depended on the feed formulation but was unaffected by the process conditions.ConclusionThis study demonstrated that drying nanocapsules using silica as auxiliary agent by spray drying process enables the obtaining of dried micronic particle size. The optimization of the process and the formulation variables resulted in a considerable improvement of product yield while minimizing the moisture content.

Photocatalytic Degradation of Diuron: Experimental Analyses and Simulation of HO° Radical Attacks by Density Functional Theory Calculations

The photocatalytic oxidation of diuron has been performed in presence of TiO(2) suspensions. To better understand the mechanistic details of the hydroxyl radical attack on diuron, computational methods were carried out. The combination of experimental and computational methods has been employed to establish the main degradation pathways of diuron. After identification of the majority of first byproduct, the experimental study underlined that substitution of chlorines and hydroxylation by hydroxyl radicals are the main diuron degradation pathways, in agreement with MOPAC and DFT simulations carried out in the gas phase. In addition, these calculations revealed that the aromatic ring attack is led by a HO degrees addition and not a hydrogen abstraction and the main first byproduct, monochlorohydroxylated compounds, are obtained by concerted reactions.

Improvement of an encapsulation process for the preparation of pro- and prebiotics-loaded bioadhesive microparticles by using experimental design

The purpose of this study was to design a new vaginal bioadhesive delivery system based on pectinate-hyaluronic acid microparticles for probiotics and prebiotics encapsulation. Probiotic strains and prebiotic were selected for their abilities to restore vaginal ecosystem. Microparticles were produced by emulsification/gelation method using calcium as cross-linking agent. In the first step, preliminary experiments were conducted to study the influence of the main formulation and process parameters on the size distribution of unloaded microparticles. Rheological measurements were also performed to investigate the bioadhesive properties of the gels used to obtain the final microparticles. Afterwards an experimental design was performed to determine the operating conditions suitable to obtain bioadhesive microparticles containing probiotics and prebiotics. Experimental design allowed us to define two important parameters during the microencapsulation process: the stirring rate during the emulsification step and the pectin concentration. The final microparticles had a mean diameter of 137μm and allowed a complete release of probiotic strains after 16h in a simulated vaginal fluid at +37°C.

Mucoadhesion evaluation of polysaccharide gels for vaginal application by using rheological and indentation measurements

The influence of hyaluronic acid (HA) and fructooligosaccharides (FOS) addition on low methyl pectin (LMP) gelation has been investigated in order to produce adhesive gel-based microparticles suitable for the development of a vaginal delivery system of pro- and prebiotics. First, dynamic rheological measurements were performed on LMP/Ca(2+) gels with or without FOS and HA in presence or not of porcine stomach mucins. This rheological method is known to translate the interactions between polymer and mucins and then simulate the polymer bioadhesion potential. Nevertheless, as this method is disputed, in vitro and ex vivo indentation test measurements were also achieved in order to correlate the results obtained. Despite some different results, the overall tendency indicates that addition of HA and FOS enhanced the mucoadhesive properties of LMP gels. Moreover, gel-based microparticles obtained according to an emulsification/gelation method and composed by LMP 3% (w/v), FOS 5% (w/v) and HA 0.5% (w/v) displayed a mucoadhesive potential adapted to vaginal delivery system.

Quantitative structure–activity relationship to predict acute fish toxicity of organic solvents

REACH regulation requires ecotoxicological data to characterize industrial chemicals. To limit in vivo testing, Quantitative Structure-Activity Relationships (QSARs) are advocated to predict toxicity of a molecule. In this context, the topic of this work was to develop a reliable QSAR explaining the experimental acute toxicity of organic solvents for fish trophic level. Toxicity was expressed as log(LC50), the concentration in mmol.L(-1) producing the 50% death of fish. The 141 chemically heterogeneous solvents of the dataset were described by physico-chemical descriptors and quantum theoretical parameters calculated via Density Functional Theory. The best subsets of solvent descriptors for LC50 prediction were chosen both through the Kubinyi function associated with Enhanced Replacement Method and a stepwise forward multiple linear regressions. The 4-parameters selected in the model were the octanol-water partition coefficient, LUMO energy, dielectric constant and surface tension. The predictive power and robustness of the QSAR developed were assessed by internal and external validations. Several techniques for training sets selection were evaluated: a random selection, a LC50-based selection, a balanced selection in terms of toxic and non-toxic solvents, a solvent profile-based selection with a space filling technique and a D-optimality onions-based selection. A comparison with fish LC50 predicted by ECOSAR model validated for neutral organics confirmed the interest of the QSAR developed for the prediction of organic solvent aquatic toxicity regardless of the mechanism of toxic action involved.

Photochemical behaviour of propranolol in environmental waters: the hydroxylated photoproducts

The UV irradiation of propranolol, one of the beta-blockers currently used in cardiac medicine, was studied. During irradiation, the samples were analysed by LC/MS/MS, using a Waters Symmetry C18 (3.5 µm 150 × 2.1 mm) column. The main photoproducts were identified from mono-, di- and tri-hydroxylation of the propranolol naphthalenic skeleton. Hydroxyl group positions were predicted by means of theoretical calculations. Partial charge calculations of the propranolol atoms predicted the formation of four mono-hydroxylated compounds, two of them being the most probable. From these two compounds, three di-hydroxylated compounds were predicted. Then the calculations from the two most probable di-hydroxylated compounds were used to propose three tri-hydroxylated propranolol compounds. It was found that the same hydroxylated photoproducts are formed in pure water and in treatment plant waste water.

Integrity characterization of myoglobin released from poly(ε-caprolactone) microspheres using two analytical methods: UV/Vis spectrometry and conductometric bi-enzymatic biosensor

Myoglobin (Mb)-loaded poly(ε-caprolactone) (PCL) microparticles were prepared by multiple emulsion with solvent extraction/evaporation method under more or less deleterious operating conditions. The protein integrity was monitored using both UV/Vis absorbance ratio method at specific wavelengths and a conductometric bi-enzymatic biosensor based on proteinase K and pronase. Under standard operating conditions, Mb remained in native conformation, while different degrees of protein denaturation were observed by changing the encapsulation conditions. It was shown that solvent elimination under reduced pressure and in a lower extent addition of a higher molecular weight PCL led to protein alteration. In the first case, the loss of protein integrity can be attributed to residual solvent entrapped in particles whose solidification was accelerated. In the second case, denaturation may be explained by an increase in the protein exposure time at water/organic solvent interface due to an increase in organic phase viscosity.

Data-handling strategies for metabonomic studies: example of the UHPLC-ESI/ToF urinary signature of tetrahydrocannabinol in humans

AbstractMetabonomics has become a very valuable tool and many research fields rely on results coming out from this combination of analytical techniques, chemometric strategies, and biological interpretation. Moreover, the matrices are more and more complex and the implications of the results are often of major importance. In this context, the need for pertinent validation strategies comes naturally. The choice of the appropriate chemometric method remains nevertheless a difficult task due to particularities such as: the number of measured variables, the complexity of the matrix and the purposes of the study. Consequently, this paper presents a detailed metabonomic study on human urine with a special emphasis on the importance of assessing the datas quality. It also describes, step by step, the statistical tools currently used and offers a critical view on some of their limits. In this work, 29 urine samples among which 15 samples obtained from tetrahydrocannabinol (delta-9-tetrahydrocannabinol)-consuming athletes, 5 samples provided by volunteers, and 9 samples obtained from athletes were submitted to untargeted analysis by means of ultra high-pressure liquid chromatography–electrospray ionization–time-of-flight mass spectrometry. Next, the quality of the obtained data was assessed and the results were compared to those found in databases. Then, unsupervised (principal component analysis (PCA)) and supervised (ANOVA/PCA, partial least-square–discriminant analysis (PLS-DA), orthogonal PLS-DA) univariate and multivariate statistical methods were applied. Figureᅟ

Characterization of surfactant complex mixtures using Raman spectroscopy and signal extraction methods: Application to laundry detergent deformulation.

This paper presents the analysis of surfactants in complex mixtures using Raman spectroscopy combined with signal extraction (SE) methods. Surfactants are the most important component in laundry detergents. Both their identification and quantification are required for quality control and regulation purposes. Several synthetic mixtures of four surfactants contained in an Ecolabel laundry detergent were prepared and analyzed by Raman spectroscopy. SE methods, Independent Component Analysis and Multivariate Curve Resolution, were then applied to spectral data for surfactant identification and quantification. The influence of several pre-processing treatments (normalization, baseline correction, scatter correction and smoothing) on SE performances were evaluated by experimental design. By using optimal pre-processing strategy, SE methods allowed satisfactorily both identifying and quantifying the four surfactants. When applied to the pre-processed Raman spectrum of the Ecolabel laundry detergent sample, SE models remained robust enough to predict the surfactant concentrations with sufficient precision for deformulation purpose. Comparatively, a supervised modeling technique (PLS regression) was very efficient to quantify the four surfactants in synthetic mixtures but appeared less effective than SE methods when applied to the Raman spectrum of the detergent sample. PLS seemed too sensitive to the other components contained in the laundry detergent while SE methods were more robust. The results obtained demonstrated the interest of SE methods in the context of deformulation.