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Biomedical subjects

R Phan-Tan-Luu

Publications and source records attributed to R Phan-Tan-Luu.

9 recordsLinked to original sources

Optimization of a microwave-assisted extraction method for the analysis of polycyclic aromatic hydrocarbons from fish samples.

A microwave-assisted extraction (MAE) procedure has been developed and optimized for the extraction of six regulated polycyclic aromatic hydrocarbons (PAHs) from muscle samples of polluted fish. The procedure involves the simultaneous microwave-assisted extraction of PAHs with n-hexane and the lipids hydrolysis with potassium hydroxide. Experimental design methodology allows a quick and robust optimization of operational parameters such as the extraction time, temperature, and solvent volumes. In these final optimized conditions, the procedure can be applied to a vast range of fat containing fish samples without significant changes, thus enabling its routine use. Recoveries around 90% for the studied compounds benz[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h]anthracene, and indene[1,2,3-cd]pyrene and quantification limits (between 0.07 and 0.53 ng/g dry weight) far below the regulated limits, have been obtained. The procedure is applied to several different fish samples. Further, accuracy validation using NIST SRM 2977 reference material was carried out.

Animals↗

Texture optimization of water-in-oil emulsions.

The aim of this research is to demonstrate the effect of variations in certain parameters of the oily phase (OP) in water-in-oil (W/O) emulsions on rheological and texture properties of finished products. The formulated emulsions were selected according to an optimal experimental procedure. The applied variations were nature of the OP, its volume fraction, the hydrophilic-lipophilic balance (HLB) value, and the surfactant proportion. Results are presented for the followed tests carried out on the emulsions: texture analysis, rheology, and particle size analysis. The oils used in the study were sweet almond oil, liquid paraffin, maize oil, cyclomethicone, dimethicone, and wheat germ oil. The resulting data demonstrate a notable influence of the volume fraction oil on hardness, viscosity, adhesiveness, and cohesiveness of W/O emulsions. Emulsion hardness and viscosity increased as the OP percentage increased; this effect being even more pronounced for the vegetable oils. In contrast, emulsion adhesiveness and cohesiveness decreased as the volume fraction oil increased. The HLB value of the surfactant mixture of the emulsion also influenced hardness, adhesiveness, and elasticity, increasing or decreasing as HLB value did.

Drug Compounding↗

An experimental design methodology applied to the enantioseparation of a non-steroidal anti-inflammatory drug candidate.

An experimental design methodology has been applied to the enantioseparation of a new synthesized aryl propionic acid of pharmaceutical interest, namely 2-[(4'-benzoyloxy-2'-hydroxy)phenyl-propionic acid] (DF-1770y) by chiral capillary zone electrophoresis (CCZE). The chiral separation of the studied compound has been achieved employing vancomycin as the chiral selector. The partial filling-counter current method has been used in order to avoid the presence of the absorbing chiral selector in the path length of the detector and to increase the method sensitivity. A central composite design has been employed to optimize the experimental conditions for a fast separation of the enantiomers of the new synthesized aryl propionic acid. Critical parameters such as chiral selector concentration, pH and temperature have been studied to evaluate how they affected responses such as resolution and migration times. The desirability function approach has been employed in order to find the best compromise between the different experimental responses. The proposed CCZE method provided the baseline enantioseparation of the investigated drug. A Britton-Robinson buffer at pH 6.4 supplemented with 7 mM of vancomycin at 22 degrees C and -20 kV were the optimum experimental conditions allowing to achieve the highest enantioresolution of DF-1770y in less than 8.5 min.

Anti-Inflammatory Agents, Non-Steroidal↗

Optimization methods in chromatography and capillary electrophoresis.

Many methods have been developed in order to optimize the parameters of interest in either chromatography or capillary electrophoresis. In chemometric approaches experimental measurements are performed in such a way that all factors vary together. An objective function is utilized in which the analyst introduces the desired criteria (selectivity, resolution, time of analysis). Simplex methods and overlapping resolution maps are declining. Factorial designs and central composite designs are more and more popular in electrodriven capillary separations since the number of parameters to master is much larger than in either GC or LC. The use of artificial neural networks is increasing. The advantage of chemometrics tools is that no explicit models are required, conversely the number of experiments to perform may be high and boundaries of the domain are not straightforward to draw and the approach does more than is required. When models are available optimization is easier to perform by regression methods. Computer assisted methods in RPLC are readily available and work well but are still in infancy in CE. Linear solvation energy relationships seem a very valuable tool but estimates of coefficients still require many experiments.

Chromatography, Liquid↗

Screening of high shear mixer melt granulation process variables using an asymmetrical factorial design.

The effects of process conditions on the granulometric characteristics of a placebo formulation prepared in a 10 l high shear mixer by single-step melt granulation were studied. The factors under investigation were: binder grade, mixer load, presence of the deflector (all of analysed at two levels), binder concentration, impeller speed, massing time, type of impeller blades (these four at three levels) and jacket temperature (considered at four levels). Two granule characteristics were analysed: the geometric mean diameter and the percentage of particles finer than 315 microm. In order to screen simultaneously the above-mentioned factor levels, an asymmetrical factorial design was adopted, which allowed the reduction in the number of runs from 2592 to 25. Additionally, this technique permitted the selection of the factor levels which have the major 'weight' on the two granule characteristics under study. Two additional trials were performed to attest the screening validity.

Chemistry, Pharmaceutical↗

Development of 5-iodo-2'-deoxyuridine milling process to reduce initial burst release from PLGA microparticles.

The aim of this study was to prepare 5-iodo-2'-deoxyuridine (IdUrd) loaded poly(d,l-lactide-co-glycolide) (PLGA) microspheres with a reduced initial burst in the in vitro release profile, by modifying the drug grinding conditions. IdUrd particle size reduction has been performed using spray-drying or ball milling. Spray-drying significantly reduced drug particle size with a change of the initial crystalline form to an amorphous one and led to a high initial burst. Conversely, ball milling did not affect the initial IdUrd crystallinity. Therefore, the grinding process was optimized to emphasize the initial burst reduction. A first step allowed us to set qualitative parameters such as ball number (7) and cooling with liquid nitrogen to obtain a mean size reduction and a narrow distribution. In a second step, three parameters including milling speed, drug amount and time were studied by a response surface analysis. The interrelationship between drug amount and milling speed was the most significant factor. To reduce particle size it should be necessary to use a moderate speed associated with a sufficient drug amount (400-500 mg). IdUrd release from microparticles prepared by the o/w emulsion/extraction solvent evaporation process with the lowest crystalline particle size (15.3 microns) was studied. Burst effect could be reduced significantly. Concerning the first phase of drug release, the burst was 8.7% for 15.3 microns compared to 19% for 19.5 microns milled drug particles.

Chemistry, Pharmaceutical↗

Experimental design for a pharmaceutical formulation: optimisation and robustness.

In pharmaceutical industries, the formulator is usually faced with the optimisation of the excipient mixture composition aimed to prepare a product with the required characteristics. Experimental research methodology represents an efficient approach for solving such optimisation problems. Planning mixture experiments using specific designs allows to analyse the blending properties of each mixture component and estimate an empirical model approximating the response of interest as a function of excipient proportions. In this study the evolution of theophylline solubility in a four-component system with constraints was analysed using two mixture design approaches: a classical mixture component proportion approach and a mathematically independent variable approach. An optimal region characterised by high solubility values was found and further explored in order to verify the insensitivity of theophylline solubility to slight variations of the excipient mixture composition.

Chemistry, Pharmaceutical↗

Experimental design in the development of voltammetric method for the assay of omeprazole.

A multivariate strategy was used to optimize an adsorptive stripping voltammetric method for the determination of the antiulcer drug omeprazole. A 3/4 matrix was used for the variable screening while a central composite design was chosen in the subsequent step to evaluate the response surfaces. Simultaneous optimization of the response peak height (hp) and peak half width w1/2), the latter being a peak shape measure, was achieved. The factors accumulation time, pulse amplitude, scan rate and stirring rate were all found to be statistically significant for the response hp, while for the response w1/2 only the stirring rate was found to be significant. The optimized method shows a good linearity between peak height and analyte concentration in the concentration range from 8.33 x 10(-9) M to 1.42 x 10(-7) M with a LOD of 6.5 x 10(-9) M. The mean recovery of omeprazole in capsules was 101.9% with a SD of 2.04 (RSD = 200).

Adsorption↗

Influence of experimental parameters on the microencapsulation of a photopolymerizable phase.

Conditions of microencapsulation by in situ polycondensation, using melamine-formaldehyde as wall material, are influenced by the chemical nature of the core to encapsulate. In our study concerning the encapsulation of a photopolymerizable phase containing an electrically charged compound, it was necessary to modify the experimental process to obtain capsules of good quality. We used the factorial design method of screening by utilization of an asymmetric matrix, according to the collapsing principle of Addleman. The advantage of this method is that it allows determination of the simultaneous influences of the 11 experimental parameters involved in this preparation. The calculation method can be applied to more than two levels for some of the factors. The continuously varying parameters were altered between two extreme levels, chosen to allow encapsulation. For discontinuous factors, such as the molecular weight of the modifying system or nature of the aminoplast, we used the commercially available compounds, respectively three and four kinds. The results of the obtained capsules were determined by comparing microphotographic pictures. With 16 experiments we found four more factors influencing quality of capsules. We also determined the most favourable levels for the other seven parameters. The results allowed us to find optimal conditions in the experimental field. We obtained capsules of a satisfactory quality for this purpose, using only minimum experimentation.

Chemistry, Pharmaceutical↗