Drug In Aqueous Solution Research Articles

Determination of osmotic coefficients and activity coefficients of calcium d-pantothenate, cefazolin sodium, and ceftriaxone sodium drugs in aqueous solutions of amino acids by using vapor pressure osmometry at 310.15 K

Fundamental and serious efforts have been made over the past years to improve the drug acts, which leads to the discovery of novel drug preparations and delivery systems. The optimal design of such processes requires a molecular-level understanding of the interactions between drug molecules and biomolecules such as proteins. The thermodynamic investigation provides deep insight and knowledge of solute-solvent interactions and selection of appropriate production compounds in pharmaceutical fields. Particularly, the study of drug + biomolecule in aqueous media is the central issue in many types of research. The osmotic coefficient data for aqueous solutions containing the drugs (calcium d-pantothenate (CDP), cefazolin sodium (CFZ.Na), ceftriaxone sodium (CFT.Na)) with simple amino acid, l-alanine, glycine and l-leucine are obtained at 310.15 K using vapor pressure osmometry. Activity coefficients of both components in mixture were estimated using experimental osmotic coefficients. According to the results, the values of osmotic coefficients for the ternary system (drug + water + l-leucine) with a concentration of 0.04 mol∙kg−1 are higher than those values in other systems. The concentration dependence of osmotic coefficients indicates ion-pair formation between the ions of the drugs. Finally, Lin et al. and ECA models were used to correlate the water activity data in the presence of the amino acids obtained for the aqueous solution (drug + water + amino acid).

Investigation of the Changes in Extinction Spectrum of Modern Chlorine-Containing Photosensitizing Drugs under the Visible Light Action

The paper presents the results of a study of the extinction spectra (350–900 nm) of aqueous solutions of modern chlorine-containing photosensitizing drugs for photodynamic therapy “Chloderm" (Chloderm, Russia) and "Chloderm with hyaluronic acid" (Chloderm, Russia) before and after irradiation by visible light with wavelengths of 405 nm, 450 nm, and 656±10 nm, with exposure time 0–20 min and intensity 0–200 mW/cm 2 . It is demonstrated that the addition of hyaluronic acid does not deform the shape of the extinction spectrum of the photosensitizing drug but reduces its absorption in proportion to the drop in the concentration of the photosensitizer in the drug. Photodynamic light action in the investigated range of parameters leads to a slight decrease in the extinction coefficient of both drugs at the wavelengths of the exposure, but significantly reduces extinction and deforms the Qy 00 absorption band (600–700 nm), thereby changing the ratio of monomers and tetramers in the drugs. This band is most significantly deformed after exposure to light with a wavelength of 656±10 nm, the least – with a wavelength of 450 nm .

Inhibition of Crystal Nucleation and Growth in Aqueous Drug Solutions: Impact of Different Polymers on the Supersaturation Profiles of Amorphous Drugs-The Case of Alpha-Mangostin.

The polymer used in supersaturated solutions plays a critical role in maintaining supersaturation levels of amorphous drugs. The prevention of drug crystallization in the supersaturated solutions by adding polymers depends on their ability to inhibit nucleation and crystal growth of drugs. This showed that understanding the mechanism of nucleation inhibition by polymers is necessary to develop the drug formulation in supersaturated solutions. Therefore, this study aims to evaluate the impact of water-soluble polymers on the supersaturation behavior of drugs and elucidate the mechanism of maintaining the supersaturation levels in an aqueous solution. It was carried out using alpha-mangostin (AM) as a model of the poorly water-soluble drug, while hypromellose (HPMC), polyvinylpyrrolidone (PVP), and eudragit were used as polymers. Their ability to inhibit the nucleation and crystal growth of AM was also evaluated. The supersaturation profiles of AM were measured in biorelevant dissolution media, while the crystal growth rate of AM was evaluated from the decrease in dissolved drug concentration by determining the induction time for AM nucleation. The interaction of AM with each polymer was evaluated and predicted by FT-IR, NMR measurement, and an in silico study, respectively. Based on observation, the PVP effectively maintained AM in a supersaturated state for the long term while eudragit conserved for 15 min. Meanwhile, an inhibitory effect of HPMC on the AM crystal nucleation was not observed. It was also \]-+discovered that the effectiveness of the various polymers depends on the interaction between the polymer and the drug. FT-IR and in silico studies demonstrated that the interaction of PVP-AM had the best polymer compared to eudragit and HPMC. NMR analysis suggested that the interaction between the methyl group from PVP with the carbonyl group of AM occurred in the PVP solution. The viscosity measurement revealed that the inhibition of nucleation and crystal growth of AM was not caused by increasing the viscosity. These results indicated that polymer-AM interactions could contribute to the crystallization inhibition and maintenance of AM in a supersaturated state. Therefore, an investigation of the mechanism of drug nucleation inhibition by polymers is recommended in the selection of crystallization inhibitors and a planned strategy to develop supersaturated formulations of drugs.

Novel pH-Responsive Cubosome and Hexosome Lipid Nanocarriers of SN-38 Are Prospective for Cancer Therapy.

Highlights1) What are the main findings? Lipid nanoparticles containing novel synthetic aminolipids were formulated. Their internal nanostructures are sensitive to pH, being an inverse hexagonal phase at pH 7.4 and a bicontinuous cubic phase at pH 4.0–pH 7.0.Poorly soluble and highly potent anticancer drug SN-38 was encapsulated successfully in the nanoparticles with a ~100-fold increase in solubility.SN-38 was released faster at a tumour-relevant acidic pH compared to neutral pH. 2) What is the implication of the main finding? Aminolipids can be incorporated into self assembled lipid nanoparticles to achieve desirable pH responsiveness.The SN-38-loaded pH-sensitive lipid nanoparticles represent a promising candidate for delivering the potent drug SN-38 to tumour sites.The pH-sensitive lipid nanoparticles in this study can be a viable alternative to the currently used irinotecan. pH-responsive nanoparticles enable the selective delivery of a chemotherapeutic agent to tumours while reducing adverse effects. Herein we synthesised four novel aminolipids and developed pH-responsive nanostructured lipid nanoparticles (LNP), which exhibited a slow-releasing hexagonal structure (H2) at physiological pH and quick release bicontinuous cubic phase (Q2) at the acidic tumour pH. The nanoparticles were used to encapsulate and control the release of the chemotherapeutic agent SN-38. High-throughput formulation techniques were employed to fabricate LNP by mixing various amounts of aminolipid with monoolein (MO). The effect of aminolipids on MO self-assembled structures was studied using small-angle X-ray scattering (SAXS) at various pH values. Out of the four studied aminolipid-MO LNP systems, the nanoparticles containing N-(Pyridin-4-ylmethyl) oleamide (OAPy-4) or N-(2(piperidin-1yl)ethyl) oleamide (OAPi-1) exhibited a pH-induced H2 to Q2 phase transition in a tumour-relevant pH range (pH 5.5–7.0). SN-38 is 1000 times more efficacious than the commercially available prodrug irinotecan. However, low solubility in water and instability at physiological pH makes it unsuitable for clinical use. SN-38 was loaded into LNP containing MO and aminolipid OAPy-4. The drug loading and entrapment efficiency were determined, and the results indicated that the aqueous solubility of SN-38 loaded in LNP dispersions was ~100 times higher compared to the solubility of the pure drug in aqueous solution. Furthermore, we demonstrated that the in vitro SN-38 release rate from LNPs was faster at lower pH (pH 5) than at neutral pH. Therefore, pH-responsive LNPs developed in this study can potentially be employed in delivering and controlling the release of the potent drug SN-38 to tumour sites.

CMC determination and thermodynamic changes of the mixture of non-steroidal anti-inflammatory drug (mefenamic acid) with anionic surfactant (SDS), and cationic surfactant (CTAB) in aqueous solution

Surface tension was measured using a platinum plate of the tensiometer for aqueous solutions of non-steroidal anti-inflammatory drugs (NSAIDs) such as mefenamic acid in concentrations of (10-3,10-2,10-10 M) to study the effect of adding surfactants on the drug solubility, which are anionic surfactant such as sodium dodecyl sulfate (SDS) and cationic surfactant such as cetyltriamonium bromide (CTAB) concentrations within range (1x10 -3 -1x10 -1 M). The effect of temperature at (313,303,293,283 K) on these aqueous solutions with Mefenamic acid has also been studied. From the plot of the concentration of aqueous solutions of surfactants with drug versus surface tension (ɣ) were obtained the critical micelle concentration (CMC). As well, the values of the Gibbs surface excess concentration (Γmax), minimum area occupied per molecule (Amin.), surface pressure at CMC (Πcmc) were determined on basis of the standard Gibbs free energy of adsorption (ΔG°ads) and the thermodynamic constants (ΔHm, ΔSm, ΔGm, ΔGads) were found at CMC for aqueous solutions.

Self-sealing MEMS spray-nozzles to prevent bacterial contamination of portable inhalers for aqueous drug delivery

Pulmonary drug delivery by portable inhalers is the gold standard in lung disease therapy. An increasing focus on environmentally friendly inhalation currently spurs the development of propellant-free devices. However, the absence of propellants in the drug creates a need for suitable sealing systems that can ensure the pathogenic safety of devices. Traditionally, liquid drug inhalers incorporate a spray nozzle and a separate check valve. Here we show a fully integrated MEMS-based spray system for aqueous drug solutions and demonstrate its bacterial safety. The device comprises a thin silicon membrane with spray orifices, which self-seal against a compliant parylene valve seat underneath. This sealing system prevents bacterial ingrowth in its default closed state, while actuation lifts the membrane from the valve seat upon pressurization and sprays an inhalable aerosol from the nozzles. To seal against bacterial contamination effectively, we found that a contact force between the valve seat and the membrane (featuring the spray nozzles) is needed. In our testing, both self-sealing and an otherwise identical unvalved version of the spray chip can be bacterially safe in continued use when thoroughly cleaned of excess fluids and subjected to low bacterial loads for brief periods. However, when directly exposed to 10^{7} CFU/ml of our test organism Citrobacter rodentium for 24 h, unvalved systems become contaminated in nearly 90% of cases. In contrast, self-sealing spray chips reduced contamination probability by 70%. This development may enable preservative-free drug formulations in portable inhalers that use propellant-free aqueous drug solutions.

A High-Throughput LC-MS/MS Method for the Simultaneous Quantification of Twenty-Seven Drug Molecules in Ocular Tissues.

The purpose of this study was to develop a validated LC-MS/MS analytical method for the simultaneous analysis of a large cassette containing a wide range of drug substances with positive, negative, or neutral charge and further apply the method to assess octanol partition coefficient and eye tissue recovery of the drug cassette. A twenty-seven-drug cassette (N-in-one) including beta blockers, NSAIDs, and corticosteroids that range from extremely hydrophilic (sotalol) to very hydrophobic (triamcinolone hexacetanide) was used to develop an LC-MS/MS assay using QTrap 4500. An LC-MS/MS method based on gradient elution, with an eighteen-minute run time including equilibration time, was developed and validated for the rapid and simultaneous quantitation of drugs with a wide range of lipophilicities. Scheduled multiple reaction monitoring was used to maximize the scan time for each peak, ensuring sufficient scans. Method validation included lower limit of quantitation (LLOQ) and intra- and inter-day reproducibility. The LLOQ ranged from 0.5 (sotalol) to 40 fmols (dexamethasone) on column with a %RSD < 20%. The method was tested by measuring octanol:water and octanol:buffer (PBS, pH 7.4) partition coefficients and by quantitation of the drug cassette extracted from rabbit aqueous humor and cornea. Measured partition coefficients correlated positively with predicted values (r2=0.5-0.7). Drug recovery was ≥ 79% from aqueous humor and between 61 and 67% on average from cornea. A rapid, sensitive LC-MS/MS method suitable for N-in-one drug delivery screening was developed for simultaneous quantification of twenty-seven drugs in aqueous solutions and eye tissues.

Experimental study of ketoconazole impregnation into polyvinyl pyrrolidone and hydroxyl propyl methyl cellulose using supercritical carbon dioxide: Process optimization

This study aims to increase the oral bioavailability of ketoconazole (KET, drug) by incorporating it into water-soluble polymers, using supercritical carbon dioxide (SC-CO2) as the impregnating solvent. For this purpose, loading of KET into poly (vinylpyrrolidone) (PVP) and hydroxy propyl methyl cellulose (HPMC) using supercritical solvent impregnation (SSI) was investigated for the first time. Box-Behnken design (BBD) was used to optimize the impregnation process. Effects of three process parameters, namely pressure (150, 200 and 250 bar), impregnation time (60, 120 and 180 min), and temperature (308, 318 and 328 K) on the loading were studied, leading to a range of 0.33%− 0.98% for KET into PVP and 0.46%− 1.41% for KET into HPMC polymer. Samples were examined using FTIR, DLS, SEM, XRD and DSC analyses. Additionally, the small particle size and the presence of polymers increased the dissolution rate of the drug in aqueous solutions up to 7.3 folds.

Precipitation Behavior of Highly Soluble Amphiphilic Drugs in Solution: Physical Instability of Drugs in Solution

Physical instability of aqueous drug solutions, such as precipitation upon storage, has so far been difficult to predict or model. Understanding the molecular basis of such phenomena can help mitigate by influencing the product composition and by providing a mechanistic basis of experimental and in silico investigations. In this study, inconsistent precipitation of a model drug, GNE-01 in aqueous solutions was investigated. Chromatographic analyses of the drug solution that showed precipitation upon storage versus the one that did not indicate lack of covalent modification or degradation of the drug, suggesting that the precipitation was a physical phenomenon. Molecular level investigations were conducted using surface tension measurement and nuclear magnetic resonance (NMR) spectroscopy. The studies revealed self-association of the weakly basic drug in solution at slightly acidic pH values which was strengthened by the presence of polyionic excipients. The role of polyionic excipients in facilitating drug precipitation on storage was indicative of shifting solution equilibria in favor of a lower solubility drug-excipient complex. This study highlighted the importance of molecular understanding in mitigating difficult to predict physical instability of self-associating drugs in solution.

Crosslinked 4-Vinylpyridine Monodisperse Functional Microspheres for Sorption of Ibuprofen and Ketoprofen

Nowadays, ibuprofen and ketoprofen are widely used over-the-counter medications to treat inflammation, fever, or pain. Their high consumption and improper disposal cause them to get into the environment and often pollute surface water. In this study, the new polymeric porous microspheres based on 4-vinylpyridine (4VP) are presented as effective sorbents for ibuprofen and ketoprofen preconcentration and removal. The porous microspheres were obtained via seed swelling polymerization with the use of two types of methacrylate crosslinkers, i.e., trimethylolpropane trimethacrylate (TRIM) and 1,4-dimethacryloiloxybenzene (14DMB). Additionally, as a reference sorbent, a copolymer of styrene and divinylbenzene was obtained. Porous structure investigations showed that the microspheres possess a specific surface area of about 100 m2/g, but noticeable differences were observed in their internal topography depending on the type of crosslinker used. Moreover, the porous structure of dry and swollen microspheres differs significantly. Swollen copolymers reveal the presence of micropores. The 4VP microspheres are characterized by high thermal stability; their initial decomposition temperature is about 300 °C. The performance of the 4VP copolymers as sorbents in aqueous solutions of drugs was evaluated in static and dynamic modes at three pH values of 3, 7, and 11. The highest sorption efficiency was obtained for ibuprofen and ketoprofen in pH 3. Both 4VP copolymers indicate the high sorption capacity in a static sorption as follows: towards ketoprofen of about 40 mg/g whereas towards ibuprofen of about 90 mg/g and 75 mg/g on copolymer crosslinked with trimethylolpropane trimethacrylate and 1,4-dimethacryloiloxybenzene, respectively. The recovery of ibuprofen and ketoprofen after dynamic sorption experiments was higher than 90%.

One-Pot, One-Step Synthesis of Drug-Loaded Magnetic Multimicelle Aggregates.

Lipid-based formulations provide a nanotechnology platform that is widely used in a variety of biomedical applications because it has several advantageous properties including biocompatibility, reduced toxicity, relative ease of surface modifications, and the possibility for efficient loading of drugs, biologics, and nanoparticles. A combination of lipid-based formulations with magnetic nanoparticles such as iron oxide was shown to be highly advantageous in a growing number of applications including magnet-mediated drug delivery and image-guided therapy. Currently, lipid-based formulations are prepared by multistep protocols. Simplification of the current multistep procedures can lead to a number of important technological advantages including significantly decreased processing time, higher reaction yield, better product reproducibility, and improved quality. Here, we introduce a one-pot, single-step synthesis of drug-loaded magnetic multimicelle aggregates (MaMAs), which is based on controlled flow infusion of an iron oxide nanoparticle/lipid mixture into an aqueous drug solution under ultrasonication. Furthermore, we prepared molecular-targeted MaMAs by directional antibody conjugation through an Fc moiety using Cu-free click chemistry. Fluorescence imaging and quantification confirmed that antibody-conjugated MaMAs showed high cell-specific targeting that was enhanced by magnetic delivery.

Identifying Small Molecule Compounds that Have Synergistic Effects With Cisplatin and Other Platinum Drugs Using High Throughput Matrix Screening

PURPOSE High grade serous ovarian cancer (“HGSOC”) is the seventh most common cancer worldwide among women. The disease has no unique symptoms and often women are diagnosed in advance stages. The World Health Organization estimates that 225,500 women are diagnosed and 140,200 will die of this disease per year. In the United States, the 5-year survival rate is 43%, and 85% of all HGSOC patients experience recurrence despite aggressive treatment. More efficacious drug combination treatments are needed. Recently it was found that platinum drugs are inactivated in dimethyl sulfoxide (DMSO). Thus drug discovery platforms that use it as a solvent are not able to study platinum drugs in combination with other drugs easily. Advances in Echo technology at the National Center for Advancing Translational Sciences (NCATS) enabled acoustic transfer of platinum drugs in aqueous solutions. This allows us to find novel small molecule/platinum drug combinations that can be tested in clinical trials. METHODS We ran single-agent dose-response experiments to correctly estimate the dose-ranges needed for the matrix screens utilizing the OVCAR8 human carcinoma cell line. Then, we conducted our pilot matrix screen with compounds that are commonly combined with cisplatin for HGSOC treatment. Lastly, we spotted cisplatin against the Mechanism Interrogation PlatE drug library to identify novel combinations for clinical use against HGSOC. Compounds that show synergistic cell killing will give insight into novel drug combinations to treat HGSOC. RESULTS Several synergistic and antagonistic effects were found. These results were refined with smaller-scale screening and tested in other HGSOC cell lines. CONCLUSION The novel combinations discovered will allow chemotherapy patients to receive lower dosages of platinum drugs while maintaining or improving efficacy of cytotoxicity of cancer cells. This will help alleviate the side-effects of platinum drugs experienced by HGSOC patients.

Design of Experiment (DOE) for Optimization of PLGA Nanoparticles

AbstractDesign of Experiments (DOE) is useful tool for formulation optimization. In present study, Design Expert® software (version 13) was used for optimization of Poly(dl‐lactide‐co‐glycolide) (50:50) (PLGA) nanoparticles (NPs). Capecitabine, an approved anticancer drug with short half‐life, was used as model drug. Capecitabine NPs can minimize dosing frequency and improve patient compliance. Effect of two numeric (drug and polymer amount) and one categoric factor (pH of W2 phase) was studied on NP Size and Entrapment Efficiency (EE). Drug amount and pH significantly influenced EE. Polymer amount significantly influenced NP size.MethodsPLGA NPs were prepared by double emulsion technique. Aqueous drug solution (W1) was emulsified with polymer solution in ethyl acetate using probe sonicator (Misonix) for 2 minutes. Formed primary emulsion was sonicated with second aqueous phase (W2) containing stabilizer Kolliphor®P188 for 1 minute to produce double emulsion. Organic solvent and excess water were evaporated at 600 rpm, 60°C for 1.5 hr and NPs were washed thrice (14,000 rpm, 4°C for 45 min) Lyophilized NPs were sonicated with acetonitrile for 5 min and EE was analyzed using UV/Vis spectrometer at ʎmax304nm. Particle size was determined using Malvern Nano‐ZS.ResultsExperimental data were fitted into models of increasing polynomial complexity. EE data is best described by two‐factor interaction model with R² of 0.9145. ANOVA results show model is significant. Predicted R²of 0.8076 is in reasonable agreement with adjusted R² of 0.8824. Drug amount, pH of W2 phase and their interaction are significant (p&lt;0.05). Higher drug amount decreases EE which maybe because polymer amount was not sufficient to encapsulate increased drug amount and more drug migrated to W2 phase. Lower EE at pH 4.5 might be described by drug leaching into W2 phase due to better drug solubility. Diagnostic normal plot, perturbation plots, interaction plots and 3D‐surface plot confirm model robustness. Size data was best fitted to linear model showing polymer amount being significant. Higher polymer amount might have decreased dispersion efficiency of first emulsion into W2 phase and led to fusion of semi‐formed particles to larger size.Numerical OptimizationThe desired goals were set to minimize polymer amount (to increase drug amount per unit weight of NPs), to minimize drug amount and the pH was set at 7.4 to maximize EE. Predicted optimum responses were checked experimentally. Batch prepared with 120mg polymer and 25mg capecitabine has average size of 111.3 nm (predicted value 116.8nm) and EE of 38% (predicted value 40%), both with 5% coefficient of variance.ConclusionDOE gives an opportunity to look at individual and combined impact of various factors. It can provide valid conclusions with minimal experimental runs, time, and cost. Similar DOE approaches can be used for other PLGA‐drug formulations optimization.Conflict of InterestAuthors declare no conflicts of interest.

Rapid Assay for the Therapeutic Drug Monitoring of Edoxaban.

Edoxaban is a direct oral anticoagulant (DOAC) that has been recently indicated for the treatment of pulmonary embolism (PE) in SARS-CoV-2 infections. Due to its pharmacokinetic variability and a narrow therapeutic index, the safe administration of the drug requires its therapeutic drug monitoring (TDM) in patients receiving the treatment. In this work, we present a label-free method for the TDM of edoxaban by surface enhanced Raman spectroscopy (SERS). The new method utilises the thiol chemistry of the drug to chemisorb its molecules onto a highly sensitive SERS substrate. This leads to the formation of efficient hotspots and a strong signal enhancement of the drug Raman bands, thus negating the need for a Raman reporter for its SERS quantification. The standard samples were run with a concentration range of 1.4 × 10−4 M to 10−12 M using a mobile phase comprising of methanol/acetonitrile (85:15 v/v) at 291 nm followed by the good linearity of R2 = 0.997. The lowest limit of quantification (LOQ) by the SERS method was experimentally determined to be 10−12 M, whereas LOQ for HPLC-UV was 4.5 × 10−7 M, respectively. The new method was used directly and in a simple HPLC-SERS assembly to detect the drug in aqueous solutions and in spiked human blood plasma down to 1 pM. Therefore, the SERS method has strong potential for the rapid screening of the drug at pathology labs and points of care.

Volumetric, acoustic and viscometric studies of solute-solute and solute-solvent interactions of glycine and its peptides in aqueous solutions of an antidepressant drug at different temperatures

From the density (ρ), speed of sound (u) and viscosity (η) measurements, the interactions of glycine, glycylglycine and glycylglycylglycine with antidepressant drug, nortriptyline hydrochloride have been investigated in aqueous medium at temperatures, T = (293.15–313.15) K and experimental pressure p = 0.1 MPa. From the experimental density measurements, apparent molar volume (VΦ), limiting apparent molar volume (VoΦ) and partial molar volumes of transfer (VoΦ,tr) have been determined for various solutions of glycine, glycylglycine and glycylglycylglycine in aqueous nortriptyline hydrochloride. In addition, using speed of sound data, apparent molar isentropic compression (Ks,Φ), limiting apparent molar isentropic compression (Kos,Φ) and partial molar isentropic compression of transfer (Kos,Φ,tr) have been calculated. Pair and triplet interaction coefficients are also determined from VoΦ,tr values using McMillan-Mayer theory. Further, apparent molar expansibility (EoΦ) and Hepler's constant values ∂EoΦ∂TP have been evaluated to assist the interpretations earned from the volumetric and acoustic analysis. The viscosity coefficients A and B, viscosity B-coefficient of transfer (Btr) and temperature derivative of B-coefficients (dB/dT) have been determined from viscosity data. The results were interpreted in terms of different kinds of intermolecular interactions present in the ternary systems (amino acid/peptides + water + nortriptyline hydrochloride) through a cosphere overlap model. The Hepler’s constant and temperature derivative of B-coefficients (dB/dT) confirms the structure breaking nature of the solute.

Thermodynamics and Micellar Behavior of Surface-Active Drugs in Aqueous Solution of Electrolytes: Surface Tension Study

Thermodynamics and Micellar Behavior of Surface-Active Drugs in Aqueous Solution of Electrolytes: Surface Tension Study

Effect of Soluplus® on γ-cyclodextrin solubilization of irbesartan and candesartan and their nanoaggregates formation

The poor aqueous solubility of irbesartan (IRB) and candesartan cilexetil (CAC) may hamper their bioavailability when orally or topically administered. Among several attempts, the promising nanoaggregate formation by γ-cyclodextrin (γCD) complexation of drugs in aqueous solution with or without water-soluble polymers was investigated. According to phase solubility studies, Soluplus® showed the highest complexation efficiency (CE) of drug/γCD complexes among the polymers tested. The aqueous solubility of IRB and CAC was markedly increased as a function of Soluplus® concentrations. The binary drug/γCD and ternary drug/γCD/Soluplus® complex formations were supported and confirmed by solid-state characterizations, including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FT-IR) spectroscopy. The true inclusion mode was also proved by proton nuclear magnetic resonance (1H-NMR) spectroscopy. The nanoaggregate size and morphology of binary and ternary systems were observed using dynamic light scattering (DLS), and transmission electron microscopy (TEM) techniques. The size of these nanocarriers depends on the concentration of Soluplus®. The use of Soluplus® could significantly enhance drug solubility and stabilize complex nanoaggregates, which could be a prospective platform for drug delivery systems.

Carbamazepine removal from aqueous solution by synthesized reduced graphene oxide-nano zero valent iron (Fe0-rGO) composite: theory, process optimization, and coexisting drugs effects.

Synthesized Fe0-rGO nanocomposite with ratio of 1/1 (w/w) was prepared and has been used as adsorbent for the removal of Carbamazepine (CBZ) from aqueous solution. The adsorbent was characterized by various techniques such as Fourier-transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and Field Emission Scanning Electron Microscopy (FE-SEM) analyses. Linear experiments were performed to compare the best fitting isotherms and kinetics. The Freundlich isotherm (R2>0.90) and pseudo second order kinetic (R2>0.99) fitted well the experimental data. On the basis of the Langmuir isotherm, the maximum adsorption capacity of Fe0-rGO for CBZ was up to 50 mg g-1 at 30 °C. The pH, adsorbent dose, and initial concentration of CBZ were observed to be the leading parameters that affected the removal of CBZ considering the analysis of variance (ANOVA; p<0.05). The optimum process value of variables obtained by numerical optimization corresponds to pH 3.07, an adsorbent dose of 36.2 mg, an initial CBZ concentration of 5 mg L-1 and at 30.15 °C. The results of optimum conditions reveal that a maximum of 94% removal efficiency can be achieved; whereas, this phenomenon was independent of temperature (p-value>0.05). Moreover, Fe0-rGO can be used to remove diclofenac (DIC) and cetirizine (CTZ) simultaneously. To sum up, the Fe0-rGO is a promising adsorbent not only for the efficient removal of CBZ but also for the reduction of coexisting drugs in aqueous solution.

Interaction studies of diglycine with aqueous solutions of sulphathiazole drug at different temperatures

The interactions of diglycine with sulphathiazole drug as a function of temperatures have been studied using volumetric and acoustic parameters. Densities and speeds of sound of diglycine in (0.001, 0.002,0.005, and 0.010) mol·kg-1 aqueous solutions of sulphathiazole drug have been measured at five different temperatures of (288.15,293.15,298.15,303.15 and 308.15) K under 0.1MPa pressure. From density data, the apparent molar volume (Vf), the partial molar volume ( ) and the standard partial molar volume of transfer ( ) for glycine from water to aqueous sulphathiazole solutions have been calculated. Partial molar isentropic compression and partial molar isentropic compression of transfer ( ) have been calculated from the speed of sound data. Transfer parameters by using cosphere overlap model have been explained from the point of view of concentration dependence of solute-solute and solute-solvent interactions. To draw the conclusion from the volumetric and acoustic data, limiting apparent molar expansion , as well as hydration numbers, have been studied. The calculated values of thermal expansion coefficient, , have small and positive values. All of these derived or calculated parameters are explained to understand the solvation behavior, mixing aspects and various types of interactions born in the ternary solutions of (drug + water + dipeptide) due to change in structure. We have also attempted to examine the temperature and concentration dependence of such interactions.

Volumetric, compressibility and viscometric properties of diphenhydramine hydrochloride in aqueous solutions of electrolytes: An insight into interactional characteristics

The density (ρ), speeds of sound (u), and viscosity (η) measurements for diphenhydramine hydrochloride (anti histaminic drug) in aqueous solutions of different electrolytes (NaCl, KCl, RbCl, MgCl2, CaCl2 and SrCl2) have been carried out. Volumetric and compressibility properties of aqueous drug solution containing electrolyte have been explained on the basis of trends observed in different enumerated parameters and information regarding various solute–solvent interactions prevailing in the ternary system have been accessed. The effect of drug concentration and temperature on the interactional behaviour of the considered system has been analyzed by carrying out the experiments at different drug content (0.03–0.17 mmol.kg−1) and temperatures (298.15–313.15) K at definite interval of 5 K. The participation of specific as well as non-specific interactions between diphenhydramine hydrochloride (DPH) and electrolytes in aqueous solution has been found to play its role in stabilization of solution mixture. Further, the structural changes induced by drug molecules in solution containing different electrolytes with same concentration have been illustrated with the help of viscosity studies. The results obtained from different employed studies have been used to elucidate solute/solvent–solvent/solute interactions in aqueous electrolytic solution. As electrolytes are integral part of biological system, hence, the study of such systems may be very useful in understanding the mechanism of drug action that ultimately facilitates the illustration of drug – electrolyte chemistry.