pH Modification Research Articles

In vitro synergistic interaction between Melaleuca armillaris essential oil and erythromycin against Staphylococcus aureus isolated from dairy cows.

Staphylococcus aureus frequently causes subclinical mastitis around the world with a high impact on the milk industry and public health. Essential oils (EO) are recognized antimicrobials that can be synergistic with antibiotics. The main objective of this study was to evaluate the essential oil (EO) of Melaleuca armillaris as an adjuvant of erythromycin (ERY) for the alternative treatment of bovine mastitis caused by S. aureus. The Minimum Inhibitory and Bactericidal Concentrations (MIC and MBC) of EO, ERY, and its combinations were established against S. aureus at different pHs (7.4, 6.5 and 5.0), emulating extra and intracellular conditions. Sensitive (N = 3) and resistant (N = 3) strains to ERY and S. aureus ATCC 29213 as control were used. Math models were applied to describe the antibacterial activity of EO and combinations EO-ERY. The EO was bactericidal against all the strains independently of the pH with a slight improvement in acid conditions. The synergism between EO and ERY was estimated by the Fractional Inhibitory Concentration Index (FIC) and by mathematical modeling of the bacterial killing data. Synergism was observed with ERY, where combinations had bactericidal activity also even with pH modification. M. armillaris EO is an interesting adjuvant for ERY, being a promissory option for further analysis of intracellular efficacy against S. aureus.

Use of Gastrointestinal Simulator, Mass Transport Analysis, and Absorption Simulation to Investigate the Impact of pH Modifiers in Mitigating Weakly Basic Drugs' Performance Issues Related to Gastric pH: Palbociclib Case Study.

It is well known that reduced gastric acidity, for example with concomitant administration of acid reducing agents, can result in variable pharmacokinetics and decreased absorption of weakly basic drugs. It is important to identify the risk of reduced and variable absorption early in development, so that product design options to address the risk can be considered. This article describes the utilization of in vitro and in silico tools to predict the effect of gastric pH, as well as the impact of adding pH modifiers, in mitigating the effect of acid reducing agents on weak base drugs' dissolution and absorption. Palbociclib, a weakly basic drug, was evaluated in low and high gastric pH conditions in a multicompartmental dissolution apparatus referred to as a gastrointestinal simulator (GIS). The GIS permits the testing of pharmaceutical products in a way that better assesses dissolution under physiologically relevant conditions of pH, buffer concentration, formulation additives, and physiological variations including GI pH, buffer concentrations, secretions, stomach emptying rate, residence time in the GI, and aqueous luminal volume. To predict drug dissolution in the GIS, a hierarchical mass transport model was used and validated using in vitro experimental data. Dissolution results were then compared to observed human clinical plasma data with and without proton pump inhibitors using a GastroPlus absorption model to predict palbociclib plasma profiles and pharmacokinetic parameters. The results showed that the in silico model successfully predicted palbociclib dissolution in the GIS under low and high gastric pH conditions with and without pH modifiers. Furthermore, the GIS data coupled with the in silico tools anticipated (1) the reduced palbociclib exposure due to proton pump inhibitor coadministration and (2) the mitigating effect of a pH-modifying agent. This study provides tools to help in the development of orally administered formulations to overcome the effect of elevated gastric pH, especially when formulating with pH modifiers.

In vitro and ex vivo evaluation of bilayered effervescent microenvironmental pH modifying buccal films with saquinavir

Buccal delivery of saquinavir has the advantage to bypass the hepatic first-pass metabolism associated with oral administration. Local microenvironmental pH (pHM) modification at the buccal mucosa might increase absorption of saquinavir by balancing the solubility and partition of saquinavir into the buccal mucosa. The present study aimed to evaluate a novel saquinavir pHM modifying buccal film using effervescence, as well as to elucidate the relationship between pHM and permeation of saquinavir released from the buccal films. Hydroxypropyl methylcellulose-based films were prepared: 1) a bilayered effervescent film composed of an alkaline layer and a layer containing saquinavir and malic acid, 2) a monolayered film composed of saquinavir and malic acid (pHM modifying film), and 3) a monolayered film composed of saquinvir (control). The release of saquinavir from these films and permeation of saquinavir across porcine mucosae were evaluated. The monolayered pHM modifying film led to a decrease in pHM from pH 6.8 to 3.0 after 5.5 min, while the effervescent film had an initial decrease in pHM (from pH 6.8 to 4.0) caused by the co-release of malic acid and a subsequent pHM increase (from pH 4.0 to 5.9) caused by the release of carbonate from the alkaline layer within 15 min. Saquinavir released faster from the pHM modifying film than from the effervescent film. However, a higher permeation of saquinavir and mucosal accumulation was observed for the effervescent film. This could be attributed to the higher concentration of ionized specie and a faster tissue partitioning of unionized saquinavir, respectively. These results suggest that effervescent pHM modifying film is a potential formulation strategy for buccal delivery of saquinavir.

Exploring the Use of Tobacco Waste as a Metal Ion Adsorbent and Substrate for Sulphate-Reducing Bacteria during the Treatment of Acid Mine Drainage

Treatment of acid mine drainage (AMD) was successfully demonstrated using tobacco waste (dust and stem) as a metal cation adsorbent, pH modifier and carbon source for sulphate-reducing bacteria (SRB). Synthetic and industrial AMD wastewaters were used in batch adsorption and SRB facilitated bioremediation experiments. Up to absorbent loading of 80 g/L, metal removal increased. However, increases above 160 g/L did not offer a proportional increase. At an adsorbent loading of 80 g/L, the highest metal removals of 38, 41, 31 and 43% for iron, nickel, copper and zinc respectively were achieved. The iron data fitted well to the Langmuir adsorption isotherm while the Sips adsorption isotherm better-described nickel, copper and zinc adsorption to tobacco waste. SRBs used were able to use tobacco waste as a carbon source while reducing sulphates to metal sulphides in acid mine drainage. In the presence of SRBs, metal removals by both adsorption and sulphide precipitation were 95, 97, 70 and 93% for iron, nickel, copper and zinc, respectively. Copper, however, demonstrated lower removal yields in both adsorption and bioremediation. Bioremediation improved acid mine drainage pH by 2.05 units. The exponential decay function could model both the metal and sulphate removal perfectly. It was concluded that tobacco waste can be confidently used as an adsorbent and carbon source for sulphate-reducing bacteria while facilitating AMD biological treatment.

Synthesis of Micron-Sized LiNi0.8Co0.1Mn0.1O2 and Its Application in Bimodal Distributed High Energy Density Li-Ion Battery Cathodes

The uniform and smaller-sized (~3 μm) LiNi0.8Co0.1Mn0.1O2 (SNCM) particles are prepared via a fast nucleation process of oxalate co-precipitation, followed by a two-step calcination procedure. It is found that the fast nucleation by vigorous agitation enables us to produce oxalate nuclei having a uniform size which then grow into micron-particles in less than a few minutes. The impacts of solution pH, precipitation time, calcination temperature, and surface modification with ZrO2 on the structural, morphological, and electrochemical properties of SNCM are systematically examined to identify the optimal synthetic conditions. A novel bimodal cathode design has been highlighted by using the combination of the SNCM particles and the conventional large (~10 μm) LiNi0.83Co0.12Mn0.05O2 (LNCM) particles to achieve the high volumetric energy density of cathode. The volumetric discharge capacity is found to be 526.6 mAh/cm3 for the bimodal cathode L80% + S20%, whereas the volumetric discharge capacity is found to be only 480.3 and 360.6 mAh/cm3 for L100% and S100% unimodal, respectively. Moreover, the optimal bi-modal cathode delivered higher specific energy (622.4 Wh/kg) and volumetric energy density (1622.6 Wh/L) than the L100% unimodal (596.1 Wh/kg and 1402.1 Wh/L) cathode after the 100th cycle. This study points to the promising utility of the SNCM material in Li-ion battery applications.

Bio-Activation of HA/β-TCP Porous Scaffolds by High-Pressure CO2 Surface Remodeling: A Novel "Coating-from" Approach.

Biphasic macroporous Hydroxyapatite/β-Tricalcium Phosphate (HA/β-TCP) scaffolds (BCPs) are widely used for bone repair. However, the high-temperature HA and β-TCP phases exhibit limited bioactivity (low solubility of HA, restricted surface area, low ion release). Strategies were developed to coat such BCPs with biomimetic apatite to enhance bioactivity. However, this can be associated with poor adhesion, and metastable solutions may prove difficult to handle at the industrial scale. Alternative strategies are thus desirable to generate a highly bioactive surface on commercial BCPs. In this work, we developed an innovative “coating from” approach for BCP surface remodeling via hydrothermal treatment under supercritical CO2, used as a reversible pH modifier and with industrial scalability. Based on a set of complementary tools including FEG-SEM, solid state NMR and ion exchange tests, we demonstrate the remodeling of macroporous BCP surface with the occurrence of dissolution–reprecipitation phenomena involving biomimetic CaP phases. The newly precipitated compounds are identified as bone-like nanocrystalline apatite and octacalcium phosphate (OCP), both known for their high bioactivity character, favoring bone healing. We also explored the effects of key process parameters, and showed the possibility to dope the remodeled BCPs with antibacterial Cu2+ ions to convey additional functionality to the scaffolds, which was confirmed by in vitro tests. This new process could enhance the bioactivity of commercial BCP scaffolds via a simple and biocompatible approach.

Caffeic Acid-Grafted PLGA as a Novel Material for the Design of Fluvastatin-Eluting Nanoparticles for the Prevention of Neointimal Hyperplasia.

Drug-eluting nanoparticles (NPs) administered by an eluting balloon represent a novel tool to prevent restenosis after angioplasty, even if the selection of the suitable drug and biodegradable material is still a matter of debate. Herein, we provide the proof of concept of the use of a novel material obtained by combining the grafting of caffeic acid or resveratrol on a poly(lactide-co-glycolide) backbone (g-CA-PLGA or g-RV-PLGA) and the pleiotropic effects of fluvastatin chosen because of its low lipophilic profile which is challenging for the encapsulation in NPs and delivery to the artery wall cells. NPs made of such materials are biocompatible with macrophages, human smooth muscle cells (SMCs), and endothelial cells (ECs). Their cellular uptake is demonstrated and quantified by confocal microscopy using fluorescent NPs, while their distribution in the cytoplasm is verified by TEM images using NPs stained with an Ag-PVP probe appositely synthetized. g-CA-PLGA assures the best control of the FLV release from NP sizing around 180 nm and the faster SMC uptake, as demonstrated by confocal analyses. Interestingly and surprisingly, g-CA-PLGA improves the FLV efficacy to inhibit the SMC migration, without altering its effects on EC proliferation and migration. The improved trophism of NPs toward SMCs, combined with the excellent biocompatibility and low modification of the microenvironment pH upon polymer degradation, makes g-CA-PLGA a suitable material for the design of drug-eluting balloons.

Novel microporous resin-based polymer device for sustained glipizide release: Production, characterization and pharmacokinetic study

The objective of this study was to explore an innovative sustained release technology and design a new microporous resin-based polymer device (RPD) for controlled release of glipizide (GZ). Photocurable resin was applied to prepare the resin layer to control GZ release. The impact of formulation parameters consisting of the type and amount of pore formers and pH modifiers, photocurable curing time as well as the weight of resin layer on GZ release were examined. The GZ-RPD was fabricated applying 24 mg of resin layer with PEG400 (100 % of the resin weight) as pore former and 10 mg of Na2CO3 as pH modifier. Scanning electron microscopy (SEM) demonstrated resin particles presenting a porous structure constituted the resin layer. The GZ-RPD possessed prolonged Tmax and reduced Cmax relative to commercial tablets. The relative bioavailability of the RPDs as well as commercial tablets was 93.65 % since the AUC0–24 h were 6111.05 ± 238.89 ng·h/mL and 6525.09 ± 760.59 ng h/mL, respectively. The release mechanism of the GZ-RPD was discussed. This paper provided an innovative concept to produce controlled GZ release oral formulation fabricated by photocurable resin, which demonstrated both excellent in vitro release and in vivo pharmacokinetics.

New Angled Twin–layer Porous Substrate Photobioreactors for Cultivation of Nannochloropsis oculata

An angled twin-layer porous substrate photobioreactor (TL-PSBR) using LED light was designed to cultivate Nannochloropsis oculata. Flocculation and sedimentation by modification of pH to 11 were determined as the optimal method for harvesting the N. oculata inoculum. The following optimised parameters were found: tilt angle 15°, Kraft 220gm-2 paper as substrate material, initial inoculum density of 12.5gm-2, 140µmol photons m-2 s-1 light intensity, and a light/dark cycle of 6:6 (h). Test cultivation for 14days was performed under optimised conditions. The total dried biomass standing crop was 75.5gm-2 growth area with an average productivity of 6.3gm-2 d-1, the productivity per volume of used culture medium was 126.2mg/L d-1, total lipid content 21.9% (w/w), and the highest productivity of total lipids was 1.33gm-2 d-1. The dry algal biomass contained 3% eicosapentaenoic acid (w/w), 3.7% palmitoleic acid (w/w), and 513mgkg-1 vitamin E. The optimisation of N. oculata cultivation on an angled TL-PSBR system yielded promising results, and applications for commercial products need to be further explored.

Development of an integrated glycine-based process for base and precious metals recovery from waste printed circuit boards

The present study developed an integrated glycine-based process to recover metals from waste printed circuit boards at high solid contents (10–15%). A novel glycine-ammonia leaching was used to selectively extract >99% copper, >85% zinc and around 50% lead at room temperature. Ammonia played a key role, increasing the copper solubility in solution (>40 g/L), shortening leaching time from 72 to 24 h, and also acting as a pH modifier. The 2nd leaching step utilised cyanide-starved glycine where extractions of 70–90% for gold and silver, and >50% for palladium were obtained. The remaining metals from the previous steps were removed by ferric sulfuric acid leaching, with/without thiourea. In the presence of thiourea, 70–95% of remaining base and precious metals were removed. Overall, the metals with major economic value were all extracted at >99% for copper, >80% for gold, >90% for silver and >85% for palladium.

Stability of Morphine Sulfate-Clonidine and Sufentanil-Clonidine Mixtures

BackgroundSpinal analgesia is recommended for intractable cancer pain. Morphine-clonidine and sufentanil-clonidine are often used in association in intrathecal drug delivery systems, injected by intraabdominal pumps. To refill these pumps and to limit patient transport, it may be necessary to ship the mixtures in polypropylene syringes to peripheral establishments located near patient homes. The purpose of this study is to determine the stability of morphine-clonidine and sufentanil-clonidine mixtures in polypropylene syringes to ensure the best and safest transport conditions and in implantable pumps for intrathecal use. Materials and MethodsThe stability study method was conceived according to the International Council for Harmonization guidelines. For polypropylene syringes, four different mixtures of morphine-clonidine and sufentanil-clonidine were assessed over seven days. Two storage temperatures were tested (5 ± 3 °C and 25 ± 2 °C). For implantable pumps, two different mixtures of morphine-clonidine and sufentanil-clonidine were assessed over 28 days and stored at 37 °C. ResultsFor the morphine-clonidine mixtures in polypropylene syringes, all mixtures remained stable for five days in both storage conditions (5 ± 3 °C and 25 ± 2 °C) because of relative concentrations systematically positioned between 90% and 110% (95% CIs of the mean of three samples). The two mixtures in implantable pumps remained stable for 28 days.For the sufentanil-clonidine mixtures in polypropylene syringes, cold conservation kept all the preparations stable for seven days, whereas a quick degradation was observed after only two days for ambient storage conditions. This result is similar to that with an implantable pump, in which the concentration is <90% on day 7 for low concentration mixtures.No visual modification, no significant pH modification, and no changes in turbidity assays were observed in either study. ConclusionThis study shows the stability of the morphine-clonidine mixtures in syringes stored at 5 °C for five days and in implantable pumps stored at 37 °C for 28 days. For the sufentanil-clonidine mixtures, the results show stability in syringes for seven days at 5 °C. Pump results show stability of seven days for low concentrations and 28 days for high concentrations.

Evaluation of a Tomato Waste Biofilter for the Retention of Gaseous Losses from Pig Slurry Hygienization by pH Modification

The use of pig slurry as organic fertilizer in intensive horticulture could be possible after hygienization to avoid contamination of products. This research aimed to evaluate a mixture of a tomato waste and rice husk as biofilter media to reduce NH3, N2O, CO2, and CH4 losses from a simple and low-cost solution for slurry hygienization by pH modification. The experiment was made in a system of laboratory scale biofilters connected to jars filled with raw slurry as control and three treatment methods: acidified slurry, alkalinized slurry, and neutralized slurry. The gas concentrations were measured for 35 days, and the composition of slurries and biofilters were determined. The results of this study showed that the mixture of biofiltering media, composed of tomato waste and rice husk, has the potential to retain NH3 and greenhouse gases (GHG) from a simple and low-cost solution for slurry hygienization by pH modification. Compared to the treatment raw slurry biofilter, the treatment neutralized slurry biofilter, subjected to a combined treatment by alkalinization/neutralization, retained 19% NH3, 4% CO2, and 83% CH4 losses and had no impact on N2O and global warming potential. Thus, the use of tomato waste biofilter during alkalinization did not increase the loss of NH3 and reduced GHG compared to raw slurry, avoiding the subsequent neutralization of slurry for environmental reasons, and could be used as an organic fertilizer in horticulture. However, using the combined alkalinization/neutralization treatment will improve the fertilizer value of the slurry by adjusting the pH from 9.5 to 7.5.

A computer vision chemometric-assisted approach to access pH and glucose influence on susceptibility of Candida pathogenic strains.

Microorganisms adapt to environmental conditions as a survival strategy for different interactions with the environment. The adaptive capacity of fungi allows them to cause disease at various sites of infection in humans. In this study, we propose digital images as responses of a complete factorial 23. Furthermore, we compared two experimental approaches: the experimental design (3D) and the checkerboard assay (2D) to know the influence of pH, glucose, and fluconazole concentration on different strains of the genus Candida. The digital images obtained from the factorial 23 were used as input in the PCA-ANOVA to analyze the results of this experimental design. pH modification in the culture medium modifies the susceptibility in some species less adapted to this type of modification. For the first time, to the best of our knowledge, digital images were used as input to PCA-ANOVA to obtain information on Candida spp.. Therefore, a higher concentration of antifungals is needed to inhibit the same strain at a lower pH. In short, we present an alternative with less use of reagents and time. In addition, the use of digital images allows obtaining information about fungal susceptibility with three or more factors.

183W Nuclear Magnetic Resonance and Photocatalysis Studies of Two Ruthenium-Decorated Isopolyoxometalates {Ru2W10} and {Ru2W13} via pH-Induced Assemblies.

Two structurally intriguing Ru-containing isopolyoxometalates [(Ru(OH))2O(W5O18)2]8- (1) and [(W5O18)(Ru2W8O31)]12- (2) were constructed from subtly different conditions. Single-crystal X-ray diffraction indicated that the precise pH modification has allowed us to trap a diruthenium-oxo core within different isopolyoxotungstate species. Compound 1 is the first sandwich-type ruthenium isopolyoxotungstate consisting of a linear {(HO)Ru-O-Ru(OH)} unit and two Lindqvist-type {W5} building blocks, while a ligand replacement of {W5} with an unusual {W8} ring in the case of compound 1 produced a unique embedded-type compound 2 with a quasi-linear {Ru-O-Ru} core. In addition to being determined in the solid state, crystal structures of 1 and 2 were also confirmed by 183W nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization-mass spectrometry (ESI-MS) in solution. 183W NMR spectrum demonstrated that the two-line pattern of 1 (with approximately 4:1 relative intensities) is consistent with the pseudo-D2h symmetry observed in the solid state. However, two other lines were observed in 2 according to the C2v symmetry but not in accord with the expected 4/4/4/1 ratio in the crystalline state, which indicated that the structure of 2 could not be maintained completely in aqueous solution. After recrystallizing the solid sample of 2 in water, the crystal structure of 2 partly converted to the structure of 1, and the transformation was determined by the combined results of 183W NMR, ESI-MS and single-crystal X-ray diffraction measurements. Catalytic investigations showed that their sodium salts presented excellent photocatalytic activities toward the benzylamine oxidation reaction induced by visible light (λ > 400 nm). The structures of the two compounds can still be maintained without a significant yield decrease after five continuous reaction cycles. Furthermore, both catalysts 1 and 2 could proceed with the oxidative coupling reaction smoothly for most of the primary benzylamine derivatives bearing various functional groups (H, F, Cl, Br, and Me) in good to excellent yields.

Scalable Production of Extracellular Vesicles and Its Therapeutic Values: A Review.

Extracellular vesicles (EVs) are minute vesicles with lipid bilayer membranes. EVs are secreted by cells for intercellular communication. Recently, EVs have received much attention, as they are rich in biological components such as nucleic acids, lipids, and proteins that play essential roles in tissue regeneration and disease modification. In addition, EVs can be developed as vaccines against cancer and infectious diseases, as the vesicle membrane has an abundance of antigenic determinants and virulent factors. EVs for therapeutic applications are typically collected from conditioned media of cultured cells. However, the number of EVs secreted by the cells is limited. Thus, it is critical to devise new strategies for the large-scale production of EVs. Here, we discussed the strategies utilized by researchers for the scalable production of EVs. Techniques such as bioreactors, mechanical stimulation, electrical stimulation, thermal stimulation, magnetic field stimulation, topographic clue, hypoxia, serum deprivation, pH modification, exposure to small molecules, exposure to nanoparticles, increasing the intracellular calcium concentration, and genetic modification have been used to improve the secretion of EVs by cultured cells. In addition, nitrogen cavitation, porous membrane extrusion, and sonication have been utilized to prepare EV-mimetic nanovesicles that share many characteristics with naturally secreted EVs. Apart from inducing EV production, these upscaling interventions have also been reported to modify the EVs’ cargo and thus their functionality and therapeutic potential. In summary, it is imperative to identify a reliable upscaling technique that can produce large quantities of EVs consistently. Ideally, the produced EVs should also possess cargo with improved therapeutic potential.

Effect of organic acid pre-treatment on polyphenol oxidase induced browning and sensory quality of frozen yam chips

Yam Dioscorea spp suffers about 30% postharvest losses annually. Processing into convenience products such as yam chips prolong shelf life although the action of enzymes including polyphenol oxidase (PPO) and peroxidase (POD) may affect the quality if not precluded. Pre-treatment of cut yam with pH modifiers and antioxidants before storage could reduce enzymatic browning. In this study we investigated the effectiveness of ascorbic acid, citric acid and lime juice treatment and 5 weeks (w) of frozen storage in reducing browning in yam chips without affecting sensory quality. PPO and POD activity of freshly prepared yam chips pre-treated with citric acid, ascorbic acid or lime juice and stored frozen at -18 °C for 5 weeks was determined. The yam chips were fried and the moisture, oil content and colour determined. Consumer acceptability sensory evaluation was conducted for the week 0 and 5 of stored samples. POD activity was significantly reduced (50%) by treatment with citric acid after five-weeks of frozen storage while treatment with ascorbic acid and lime juice had no effect on the enzyme activity. There was no significant difference in lightness between the different treatments although treated samples differed significantly from the untreated. Moisture content of all samples were lower after storage while oil content of the various treatments was significantly different. Notwithstanding these differences, consumer acceptability was not different between the various treatment and storage periods. Pre-treated frozen yam chips have a good consumer acceptance and potential for commercial application. Developing this product will add value to yams and reduce huge postharvest losses.

SYNCHRONOUS AND CONTROLLED CONVEYANCE OF METFORMIN HYDROCHLORIDE AND GLIPIZIDE CONTROLLED POROSITY OSMOTIC PUMP IN-VITRO QUANTIFICATION

In the current research, controlled porosity osmotic pump (CPOP) tablet is prepared by direct compression method and the tablet coating was achieved by a dip-coating process using chitosan as conveyance retardant to decrease the burst release time of Metformin HCl (MTF), sodium hydrogen carbonate as pH modifier and Hydroxy Propyl Methyl Cellulose (HPMC) E 15 LV as hydrophilic polymer to improve the appearance of Glipizide (GLZ) to pass on the blend of MTF and GLZ in a kept up and synchronized way. The prepared tablets were characterized for its release. The release data was fitted with release kinetics in order to determine order of release and release mechanism. The impact of release retardant shows that there is no blasted delivery of MTF was noticed upto 4th h and the delivery was controlled up to 24h and the delivery pace of GLZ was improved while joined with MTF and sodium bicarbonate. In conclusion, this methodology could be gainful for the treatment of diabetes mellitus Type 2 (DMT2) with improved disintegration.

A New Strategy for the Software-Assisted LC Separations of Ketoconazole and Its Impurities.

Analytical quality by design and the use of dissimilar chromatographic systems can be employed to accelerate chromatographic separations. Herein, a software (S-Matrix)-assisted platform was used to proficiently screen, optimize and select the optimal parameters for the chromatographic separation of ketoconazole and its related impurities. This approach evaluated the various chromatographic parameters in a stepwise manner based on the statistical tools and provided an in-depth understanding of the critical parameters influencing the peak selectivities and separations. It was demonstrated that dissimilar conditions, such as different stationary phases, mobile phase pH and organic modifiers (i.e., critical method variables), can improve the peak resolution, while the critical quality attributes can provide conditions appropriate for quantification purposes via a quality target analytical method. Furthermore, an orthogonal method was established to support the primary method. The orthogonality between the two methods was defined by the correlation matrix between the two systems using the Pearson correlation coefficient and was found to be 0.12. Using the optimized method, the primary method was validated as per International Council for Harmonization in the range of 0.05-1.0% for impurities and 80.0-120.0% for ketoconazole, thereby indicating the suitability of the method for use in quality control laboratories.

Modeling the effects of pH variation and bacteriocin synthesis on bacterial growth

Bacteriocin secretion and the modification of extracellular pH are some competitive adaptations that bacteria have acquired to persist against adverse environmental conditions. Thus, its permanence in a microbial network is determined by the adaptation that the bacterium has, therefore, directly affecting the rate of bacterial growth and its population balance. In this regard, it should be noted that bacterial secretion plays an important role in bacterial control, both intra and inter-specific, by modifying the amount of bacteria in equilibrium, while the pH determines the maximum rate of bacterial growth and the effectiveness and degradation of bacteriocins release. From the point of view of mathematical modeling, these attributes favor extending the logistic growth model as a base system for bacterial growth by incorporating a bacteriocin-bacteria association term. On the other hand, bacteriocin secretion and pH variation are based on the Luedeking-Piret function, where pH levels influence each mathematical term of bacterial growth and bacteriocin concentration. Taking all of this into account, the ordinary differential equation model emerges, which, through Lyapunov’s theory, demonstrates the stability and absence of chaos in the proposed model, while the simulations confirm it. The modeling proposed in this work has the capacity to replicate diverse scenarios of great interest, such as microbial contamination in medical supplies and the food industry.

Extraction of Gold and Copper from Flotation Tailings Using Glycine-Ammonia Solutions in the Presence of Permanganate

This study presents the novel idea of a cyanide-free leaching method, i.e., glycine-ammonia leaching in the presence of permanganate, to treat a low-grade and copper-bearing gold tailing. Ammonia played a key role as a pH modifier, lixiviant and potential catalyst (as cupric ammine) in this study. Replacing ammonia with other pH modifiers (i.e., sodium hydroxide or lime) made the extractions infeasibly low (&lt;30%). The increased additions of glycine (23–93 kg/t), ammonia (30–157 kg/t) and permanganate (5–20 kg/t) enhanced gold and copper extractions considerably. Increasing the solids content from 20 to 40% did not make any obvious changes to copper extraction. However, gold leaching kinetics was slightly better at lower solids content. It was indicated that the staged addition of permanganate was unnecessary under the leaching conditions. Recovery of gold by CIL was shown to be feasible, and it improved gold extraction by 15%, but no effect was observed for copper extraction. Percentages of 76.5% gold and 64.5% copper were extracted in 48 h at 20 g/L glycine, 10 kg/t permanganate, 20 g/L carbon, pH 10.5 and 30% solids. Higher extractions could be potentially achieved by further optimization, such as by increasing permanganate addition, extending leaching time and ultra-fine grinding.