Efficient prediction of in vitro piroxicam release and diffusion from topical films based on biopolymers using deep learning models and generative adversarial networks

The purpose of this study was to simultaneously predict the drug release and skin permeation of Piroxicam (PX) topical films based on Chitosan (CTS), Xanthan gum (XG) and its Carboxymethyl derivatives (CMXs) as matrix systems. These films were prepared by the solvent casting method, using Tween 80 (T80) as a permeation enhancer. All of the prepared films were assessed for their physicochemical parameters, their in vitro drug release and ex vivo skin permeation studies. Moreover, deep learning models and machine learning models were applied to predict the drug release and permeation rates. The results indicated that all of the films exhibited good consistency and physicochemical properties. Furthermore, it was noticed that when T80 was used in the optimal formulation (F8) based on CTS-CMX3, a satisfactory drug release pattern was found where 99.97% of PX was released and an amount of 1.18 mg/cm2 was permeated after 48 h. Moreover, Generative Adversarial Network (GAN) efficiently enhanced the performance of deep learning models and DNN was chosen as the best predictive approach with MSE values equal to 0.00098 and 0.00182 for the drug release and permeation kinetics, respectively. DNN precisely predicted PX dissolution profiles with f2 values equal to 99.99 for all the formulations

Formulation and Evaluation of Xanthan Gum Microspheres for the Sustained Release of Metformin Hydrochloride

International audienceThis work aimed to formulate xanthan gum microspheres for the encapsulation of metformin hydrochloride, according to the process of ionotropic gelation. The obtained microparticles, based on various fractions of xanthan gum (0.5–1.25), were subjected to different physico-chemical tests and a drug release study. Microspheres with an average size varying between 110.96 μm and 208.27 μm were obtained. Encapsulation efficiency reached 93.11% at a 1.25% biopolymer concentration. The swelling study showed a swelling rate reaching 29.8% in the gastric medium (pH 1.2) and 360% in the intestinal medium (pH 6.8). The drug release studies showed complete metformin hydrochloride release from the beads, especially those prepared from xanthan gum at the concentration of 1.25%, in intestinal medium at 90.00% after 6 h. However, limited and insignificant drug release was observed within the gastric medium (32.50%). The dissolution profiles showed sustained release kinetics

The Effect of the Stationary Phase on Resolution in the HPLC-Based Separation of Racemic Mixtures Using Vancomycin as a Chiral Selector: A Case Study with Profen Nonsteroidal Anti-Inflammatory Drugs

International audienceChiral resolution is a technique of choice, making it possible to obtain asymmetric and enantiomerically pure compounds from a racemic mixture. This study investigated the behavior of vancomycin when used as a chiral additive in high-performance liquid chromatography (HPLC) to separate enantiomers of nonsteroidal anti-inflammatory drugs (NSAIDs), including ketoprofen, ibuprofen, flurbiprofen, and naproxen enantiomeric impurities. We compared two achiral stationary phases (C18 and NH2) to assess the impact of mobile phase composition and stationary phase on the vancomycin retention time in the racemic resolution of drug enantiomers. Our results demonstrated the successful enantioseparation of all drugs using vancomycin in the mobile phase (phosphate buffer 0.05 M/2-propanol, 50/50) with an NH2 column. This enhanced separation on the NH2 column resulted from the chromatography system’s efficiency and vancomycin dimers’ stereoselective interaction on the NH2 surface. This study underscores the importance of stationary phase selection in the chiral resolution of NSAIDs with vancomycin as a chiral additive. It offers valuable insights for future research and development of NSAID chiral separation methods, highlighting potential vancomycin applications in this context

Evaluation of Physicochemical and Amphiphilic Properties of New Xanthan Gum Hydrophobically Functionalized Derivatives

This research aimed to develop new hydrophobic and potentially amphiphilic benzyl xanthan gum (BXG) derivatives using a Williamson synthesis. This modification consists of an etherification reaction between xanthan gum (XG) and benzyl chloride (BC) under microwave heating. The effects of the molar ratio (R = XG/CLB, with R equal to 2 or 4) on the amphiphilic character and the degree of substitution (DS) were studied. The two benzyl xanthan gum derivatives (BXG1 and BXG2) were subsequently subjected to various physicochemical and rheological characterization techniques. The obtained results of FTIR and H1-NMR spectroscopy showed the effectiveness of the grafting of aromatic moieties onto the XG molecule with DS values of 0.59 for BXG1 and 0.7 for BXG2. The XRD analysis revealed slight modifications in the xanthan crystallinity after etherification, where the degree of crystallinity (DOC) values were 8.46%, 10.18%, and 14.67% for XG, BXG1, and BXG2, respectively. Additionally, conductivity measurements showed that the BXG derivatives exhibit higher values than native XG, due to the inter- and intra-molecular associations following the grafting of aromatic groups. Moreover, the critical aggregation concentration (CAC) was detected at 0.32% for BXG1 and 0.28% for BXG2. The rheological study confirmed that XG and its BXG derivatives exhibited a shear-thinning pseudoplastic behavior and that the viscosity increases when the DS increases. The emulsifying power test of the BXGs compared to the native XG confirmed the amphiphilic properties of the new benzylated derivatives, where the stabilizing capacity increases with increased DS

Application of Walnut Shell Biowaste as an Inexpensive Adsorbent for Methylene Blue Dye: Isotherms, Kinetics, Thermodynamics, and Modeling

This research aimed to assess the adsorption properties of raw walnut shell powder (WNSp) for the elimination of methylene blue (MB) from an aqueous medium. The initial MB concentration (2–50 mg/L), the mass of the biomaterial (0.1–1 g/L), the contact time (10–120 min), the medium’s pH (2–12), and the temperature (25–55 °C) were optimized as experimental conditions. A maximum adsorption capacity of 19.99 mg/g was obtained at an MB concentration of 50 mg/L, a medium pH of 6.93 and a temperature of 25 °C, using 0.2 g/L of WNSp. These conditions showed that the MB dye elimination process occurred spontaneously. Different analytical approaches were used to characterize the WNSp biomaterial, including functional groups involved in MB adsorption, the surface characteristics and morphological features of the WNSp before and after MB uptake, and identification of WNSp based on their diffraction pattern. The experimental isotherm data were analyzed by the Langmuir and Freundlich models for the adsorption of MB dye. The corresponding values of parameter RL of Langmuir were between 0.51 and 0.172, which confirmed the WNSp’s favorable MB dye adsorption. The experimental kinetic data were examined, and the pseudo-second-order model was shown to be more suitable for describing the adsorption process, with an excellent determination coefficient (R2 = 0.999). The exchanged standard enthalpy (H° = −22.456 KJ.mol−1) was calculated using the van ‘t Hoff equation, and it was proven that the adsorption process was exothermic. The spontaneous nature and feasibility of the MB dye adsorption process on WNSp were validated by negative standard enthalpy values (G°) ranging from −2.580 to −0.469 at different temperatures. It was established that WNSp may be employed as a novel, effective, low-cost adsorbent for the elimination of methylene blue in aqueous solutions

Modeling and Optimization of Hybrid Fenton and Ultrasound Process for Crystal Violet Degradation Using AI Techniques

International audienceThis study conducts a comprehensive investigation to optimize the degradation of crystal violet (CV) dye using the Fenton process. The main objective is to improve the efficiency of the Fenton process by optimizing various physicochemical factors such as the Fe2+ concentration, H2O2 concentration, and pH of the solution. The results obtained show that the optimal dosages of Fe2+ and H2O2 giving a maximum CV degradation (99%) are 0.2 and 3.13 mM, respectively. The optimal solution pH for CV degradation is 3. The investigation of the type of acid for pH adjustment revealed that sulfuric acid is the most effective one, providing 100% yield, followed by phosphoric acid, hydrochloric acid, and nitric acid. Furthermore, the examination of sulfuric acid concentration shows that an optimal concentration of 0.1 M is the most effective for CV degradation. On the other hand, an increase in the initial concentration of the dye leads to a reduction in the hydroxyl radicals formed (HO•), which negatively impacts CV degradation. A concentration of 10 mg/L of CV gives complete degradation of dye within 30 min following the reaction. Increasing the solution temperature and stirring speed have a negative effect on dye degradation. Moreover, the combination of ultrasound with the Fenton process resulted in a slight enhancement in the CV degradation, with an optimal stirring speed of 300 rpm. Notably, the study incorporates the use of Gaussian process regression (GPR) modeling in conjunction with the Improved Grey Wolf Optimization (IGWO) algorithm to accurately predict the optimal degradation conditions. This research, through its rigorous investigation and advanced modeling techniques, offers invaluable insights and guidelines for optimizing the Fenton process in the context of CV degradation, thereby achieving the twin goals of cost reduction and environmental impact minimization

Experimental Analysis and Neural Network Modeling of the Rheological Behavior of Xanthan Gum and Its Derivatives

The main objective of this study was to create a mathematical tool that could be used with experimental data to predict the rheological flow behavior of functionalized xanthan gum according to the types of chemical groups grafted onto its backbone. Different rheological and physicochemical analyses were applied to assess six derivatives synthesized via the etherification of xanthan gum by hydrophobic benzylation with benzyl chloride and carboxymethylation with monochloroacetic acid at three (regent/polymer) ratios R equal to 2.4 and 6. Results from the FTIR study verified that xanthan gum had been modified. The degree of substitution (DS) values varying between 0.2 and 2.9 for carboxymethylxanthan gum derivatives were found to be higher than that of hydrophobically modified benzyl xanthan gum for which the DS ranged from 0.5 to 1. The molecular weights of all the derivatives were found to be less than that of xanthan gum for the two types of derivatives, decreasing further as the degree of substitution (DS) increased. However, the benzyl xanthan gum derivatives presented higher molecular weights varying between 1,373,146 (g/mol) and 1,262,227 (g/mol) than carboxymethylxanthan gum derivatives (1,326,722–1,015,544) (g/mol). A shear-thinning behavior was observed in the derivatives, and the derivatives’ viscosity was found to decrease with increasing DS. The second objective of this research was to create an ANN model to predict one of the rheological properties (the apparent viscosity). The significance of the ANN model (R2 = 0.99998 and MSE = 5.95 × 10−3) was validated by comparing experimental results with the predicted ones. The results showed that the model was an efficient tool for predicting rheological flow behavior

Elucidating Chiral Resolution of Aromatic Amino Acids Using Glycopeptide Selectors: A Combined Molecular Docking and Chromatographic Study

International audienceAn asymmetric synthesis is a favorable approach for obtaining enantiomerically pure substances, but racemic resolution remains an efficient strategy. This study aims to elucidate the chiral resolution of aromatic amino acids and their elution order using glycopeptides as chiral selectors through molecular docking analysis. Chiral separation experiments were conducted using Vancomycin as a chiral additive in the mobile phase (CMPA) at various concentrations, coupled with an achiral amino column as the stationary phase. The Autodock Vina 1.1.2 software was employed to perform molecular docking simulations between each enantiomer (ligand) and Vancomycin (receptor) to evaluate binding affinities, demonstrate enantiomeric resolution feasibility, and elucidate chiral recognition mechanisms. Utilizing Vancomycin as CMPA at a concentration of 1.5 mM enabled the separation of tryptophan enantiomers with a resolution of 3.98 and tyrosine enantiomers with a resolution of 2.97. However, a poor chiral resolution was observed for phenylalanine and phenylglycine. Molecular docking analysis was employed to elucidate the lack of separation and elution order for tryptophan and tyrosine enantiomers. By calculating the binding energy, docking results were found to be in good agreement with experimental findings, providing insights into the underlying mechanisms governing chiral recognition in this system and the interaction sites. This comprehensive approach clarifies the complex relationship between chiral discrimination and molecular architecture, offering valuable information for creating and improving chiral separation protocols

Development of New Alkylated Carrageenan Derivatives: Physicochemical, Rheological, and Emulsification Properties Assessment

In this research, amphiphilic derivatives of kappa carrageenan (KC) were synthesized by hydrophobic modification with an alkyl halide (1-Octyl chloride). Three hydrophobic polymers with different degrees of substitution (DS) were obtained by the Williamson etherification reaction in an alkaline medium. The effect of the molar ratio (R = reagent/polymer) on the DS was investigated at different ratios (1, 2, and 3). The KC derivatives (KCRs) were characterized by different techniques such as FT-IR, 1H-NMR, X-ray Diffraction, Scanning electron microscopy, and a rheological assessment. The FT-IR and 1HNMR analyses confirmed the binding of the hydrophobic groups onto the KC molecule. The degrees of substitution calculated by 1H-NMR demonstrated that the derivative KCR3 (0.68) presented a higher degree of substitution compared to KCR1(0.45) and KCR2 (0.53). The XRD and SEM analyses revealed that the alkaline etherification conditions did not alter the morphological and crystallographic properties, as well as the rheological behavior of the obtained derivatives. The amphiphilic character of the KCRs was investigated using a conductivity method which revealed that the molecular aggregation occurred above the critical aggregation concentration (CAC). Decreasing CAC values of 0.15% (KCR1), 0.11% (KCR2) and 0.08% (KCR3)with the degree of substitution (DS) were found. Furthermore, KCR’s derivatives greatly improved the stability of oil/water emulsions as the droplet size decreased with increasing DS. The derivative (KCR3) with higher DS, showed a greater amphiphilic character, and improved emulsifying power