Drug In Aqueous Solution Research Articles

Simultaneous oxidative determination of antibacterial drugs in aqueous solutions using an electrode modified with MWCNTs decorated with Fe3O4 nanoparticles

The present study describes a simple sensor developed from Fe3O4 and MWCNT nanoparticles for the simultaneous detection of sulfamethoxazole (SMX) and trimethoprim (TMP).

Effect of fruit and milk sugars on solute–solvent interactions of diphenhydramine-hydrochloride drug in aqueous solutions in viewpoint of volumetric and transport properties

Abstract The effect of (D−)-fructose (fruit sugar), (D+)-galactose and (D+)-lactose (milk sugar) on the solute–solvent interactions occurred between the diphenhydramine-hydrochloride (DPH-HCl) drug and water was studied. To this end, the density, speed of sound and viscosity data for DPH-HCl drug in water and aqueous solutions of (D−)-fructose, (D+)-galactose and (D+)-lactose should have been measured. Thermodynamic properties such as the apparent molar volume (Vϕ) and apparent molar isentropic compression (Ks,m) were calculated from the density and speed of sound values within sugar molality range of (0.05, 0.1, and 0.15) mol kg−1 at T = (288.15, 293.15, 298.15, 308.15 and 318.15) K. Extrapolation to the infinite dilution of Vϕ and Ks,m values with using Redlich–Meyer equation was applied to find the corresponding limiting apparent molar quantities. Jones–Dole equation was used to obtain the viscosity B-coefficients. Interparticle interactions occurred between the DPH-HCl drug and water were determined by calculating the transfer parameters of limiting apparent molar volume and viscosity B-coefficient from DPH-HCl in water to the DPH-HCl in aqueous (D−)-fructose, (D+)-galactose and (D+)-lactose solutions.

Development and characterization of porous bioceramic tablets based on bone powder for medical applications

Multifunctional porous biological hydroxyapatite (b-Hap) tablets prepared from fine bone powder (FBP) are predicted to be useful as a calcium supplement and at the same time as low-dose drug carriers. FBP was hydrothermally extracted, then mechanically compressed and sintered without using chemical additives to prepare the porous b-Hap tablets. The properties of FBP and b-Hap tablets were characterized by XRD, FTIR, SEM, mechanical, and porosity tests. Moreover, an aqueous drug solution of atenolol was used to evaluate release behavior from porous b-Hap tablets. The prepared FBP exhibited microstructures with grain sizes of about 50 to 100 μm while b-Hap tablets sintered at 800 °C exhibited high porosity (55%) and compression strength of 8.5 MPa. When the atenolol-loaded b-Hap tablets were immersed in the acidic medium, the release of atenolol from the tablets continued for 120 min with complete dissolution of the b-Hap tablets. These results indicate that the porous b-Hap tablets are promised as an economic calcium supplement and as low-dose drug carriers.

Rapid discrimination and quantification analysis of five antineoplastic drugs in aqueous solutions using Raman spectroscopy

The aim of this study was to assess the ability of Raman spectroscopy to discriminate and quantify five antineoplastic drugs in an aqueous matrix at low concentrations before patient administration.Five antineoplastic drugs were studied at therapeutic concentrations in aqueous 0.9% sodium chloride: 5-fluorouracil (5FU), gemcitabine (GEM), cyclophophamide (CYCLO), ifosfamide (IFOS) and doxorubicin (DOXO). All samples were packaged in glass vials and analyzed using Raman spectrometry from 400 to 4000cm−1. Discriminant analyses were performed using Partial Least Squares Discriminant Analysis (PLS-DA) and quantitative analyses using PLS regression.The best discrimination model was obtained using hierarchical PLS-DA models including three successive models for concentrations higher than the lower limit of quantification (0% of fitting and cross-validation error rate with an excellent accuracy of 100%). According to these hierarchical discriminative models, 90.8% (n=433) of external validation samples were correctly predicted, 2.5% (n=12) were misclassified and 6.7% (n=32) of the external validation set were not assigned. The quantitative analysis was characterized by the RMSEP that ranged from 0.23mg/mL for DOXO to 3.05mg/mL for 5FU. The determination coefficient (R2) was higher than 0.9994 for all drugs evaluated except for 5FU (R2=0.9986).This study provides additional information about the potential value of Raman spectroscopy for real-time quality control of cytotoxic drugs in hospitals. In some situations, this technique therefore constitutes a powerful alternative to usual methods with ultraviolet (UV) detection to ensure the correct drug and the correct dose in solutions before administration to patients and to limit exposure of healthcare workers during the analytical control process.

In vitro dissolution testing of parenteral aqueous solutions and oily suspensions of paracetamol and prednisolone

The number of intramuscularly applied dosage forms has been continuously increasing during the last decades. However, up to date no in vitro dissolution test method for parenteral dosage forms has been described in the Ph. Eur. or USP. It was the aim of this study to investigate dissolution test setups based on the compendial flow-through cell and the reciprocating holder for this purpose. Both apparatuses were equipped with dialysis membranes to accommodate the drug formulation. The suitability of the dissolution method was evaluated by comparing release profiles with blood level curves that were obtained previously in an in vivo study in rats by our group. Aqueous solutions and oily suspensions of paracetamol and prednisolone were tested in vitro that were also applied in the in vivo study. In the case of the aqueous solutions in which no formal dissolution occurs, transport from the applied depot across a dialysis membrane was investigated. While the drug transport across the dialysis membrane of both drugs in aqueous solution was similar in all applied test methods, differences in the release behavior of paracetamol and prednisolone as an oily suspension were observed. This was mainly due to sedimentation of the particles within the oily depot.

Molecular modeling, pK a and thermodynamic values of asthma drugs

This study investigates on optimized structure, pK a values and thermodynamic properties of four asthma drugs, e.g., salbutamol, terbutaline, salmeterol, and formoterol, in aqueous solution using ab initio and DFT methods at different temperatures. The molecular conformations and solute–solvent interactions of the cations, neutrals, and anions molecules of the drugs were investigated. Further, the best ionization reaction and Tomasi’s method at the B3LYP/6-31 + G(d) level of theory were used to calculate ∆G and pK a values. For the validation, the pK a values and ionization mechanisms of salbutamol and terbutaline are calculated. Furthermore, ionization schemes are proposed for formoterol and salmeterol drugs, and their pK a values at different temperature are calculated. Moreover, the chemical reactions tendency calculation showed that net electrophilicity of terbutaline, the chemical potential of salbutamol, and electronegativity of formoterol were more than the other four asthma drugs in this work. Theoretical calculation of HOMO–LUMO gap shows that the maximum and minimum gaps were for salbutamol and terbutaline, respectively. Besides, charge density distribution and site of chemical reactivity of the asthma drugs are studied by mapping electron density isosurface with molecular electrostatic potential (MEP). Also, thermodynamic properties of the drugs in aqueous solution show negative values for ∆S and positive values for ∆G.

Mixed micellization study of ibuprofen (sodium salt) and cationic surfactant (conventional as well as gemini)

AbstractHerein, we have studied the interaction between cationic surfactant (conventional [myristyltrimethylammonium bromide, MTAB] as well as gemini surfactant 1, 4‐butanediyl‐α, ω‐bis(dimethyltetradecylammonium bromide) (14‐4‐14)) and anti‐inflammatory sodium salt of ibuprofen (IBU) drug in aqueous solutions by using tensiometry method at 298.15 K. The means of the interaction of drugs by added foreign materials is of paramount importance in the drug delivery. Ibuprofen is used for the relief of pain, fever, and swelling. From this study we have evaluated different parameters, for example, critical micelle concentration (cmc), micellar mole fraction of mixed micelles/mixed interface (X1m/X1σ), micellar/surface interaction parameter (βm/βσ), activity coefficients (f1m/f1σ and f2m/f2σ) of the mixed micelles/mixed interface, excess Gibbs free energy of mixed monolayer/mixed micelle formation ( / ), surface excess concentration (Γmax) etc. and discussed in detail. The micellar interaction parameter (βm) was determined from the critical micelle concentration values of the pure surfactant (MTAB/14‐4‐14) and IBU (cmc1 and cmc2) and the mixed system (cmc) using the Rubingh's model. In addition to this, various other parameters such as packing parameters of amphiphiles in the micelles (P), volume contribution of the hydrophobic chain (V0), and its effective length (lc), have also been calculated. The value of micellar mole fraction ( ) is found to be more for IBU + 14‐4‐14 mixtures as compared to IBU + MTAB mixtures at lower mole fraction and vice versa at a higher mole fraction of surfactant. The ΔGom and ΔGoads values for all studied systems were found out to be negative, ie, micellization, as well as adsorption processes, are found to be energetically favorable.

Effect of the surface layer on drug release from delefilcon-A (Dailies Total1®) contact lenses

Contact lenses are receiving significant attention for delivering ophthalmic drugs with higher bioavailability compared to eye drops. Here we explore drug transport from delefilcon-A Dailies Total1® lenses which are designed to have a thin, high-water content layer on the surface. Our goal is to determine the impact of this high water content layer on drug transport for both hydrophobic (dexamethasone and cyclosporine) and hydrophilic (timolol and levofloxacin) drugs. Drugs were loaded into the lens by soaking in aqueous drug solutions till equilibrium, followed by release in phosphate buffered saline. The concentration data during release was fitted to the diffusion equation without considering the surface layer. If fits were poor, the surface layer was include in the model, as a burst release. Results showed that surface layer resulted in a burst release of about 35% of the loaded drug for the two hydrophilic drugs, and the model did not fit the data unless the surface layer was incorporated as a burst release. For the hydrophobic drugs, there was no burst release and the model fitted the data without including the surface layer likely because of the low partition coefficient of the hydrophobic drugs in the surface layer compared to the lens. The results further confirm the presence of the high water content surface layer on the Dailies Total1® lenses. The release profile of the burst release for hydrophilic drugs could be therapeutically useful for antibiotics where a high dose is desirable initially. The effect of vitamin E loading—an established procedure for increasing drug release time in other commercial lenses, was also tested on the release of timolol maleate and levofloxacin. A 20% vitamin E loading was found to increase the release time of timolol and levofloxacin by a factor of 5 and 3-fold respectively, but this increase proved much less effective compared to vitamin E’s effect on other commercial silicone hydrogels.

Effects of cyclodextrins on the chemical stability of drugs

Cyclodextrins (CDs) are enabling pharmaceutical excipients that can enhance both solubility and stability of wide variety of drugs in aqueous solutions through formation of drug/CD inclusion complexes where apolar moieties of the drug molecules are located inside the CD cavity. In properly designed pharmaceutical formulations CDs will improve physiochemical properties of lipophilic drugs without affecting their intrinsic ability to permeate biological membranes. Here the effect of CD complexes on the chemical stability of drugs is reviewed. Numerous studies shown that in aqueous solutions CD complexation can hamper hydrolysis, oxidation, photodegradation, isomerization and enzyme catalyzed degradation of dissolved drugs. However, some drugs, such as β-lactam antibiotics, can under certain conditions undergo CD catalyzed degradation in aqueous solutions. Also, some drugs that are stabilized by CDs in aqueous solutions are destabilized by the same CDs in solid dosage forms. Thus, the effects of CDs on drug stability have to be tested and verified in the final drug formulation and under the recommended storage conditions.

Photochemical Degradation of Fluocinolone Acetonidin Drug in Aqueous Solutions Using Nanophotocatalyst ZnO Doped by C, N, and S

It has been shown that the photocatalytic activity of doped semiconductor with some nonmetals is higher than a pure semiconductor. Hence, with an attempt to achieve higher photocatalytic activity, doped ZnO with C, N, and S was prepared by a sedimentary process and used for the photocatalytic degradation of Fluocinolone Acetonidin as a drug in aqueous solutions. X-Ray Diffraction (XRD), Energy Dispersion X-ray (EDX), X-ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM) were used to characterize the microstructure and morphology of the precursor and the products. The photocatalytic degradation of the drug was investigated using supported ZnO/C, N, and S photocatalyst under UV light irradiation. We also studied the influence of the basic photocatalytic parameters as well as irradiation time, the initial concentration of the drug, pH of the solution, amount of nanoparticles and addition of oxidant on the reaction. The optimum conditions of degradation were obtained accordingly: concentration of Fluocinolone Acetonidin, 20 ppm; the amount of photocatalyst, 7 mg; oxidant (K2S2O8), 5 mM; irradiation time, 6 h in pH=9. Kinetic analysis demonstrated that the amount of Fluocinolone Acetonidin photocatalytic degradation can be fitted by a pseudo-first-order model.

Effect of NaCl and KCl on volumetric and acoustic behaviour of procaine hydrochloride in aqueous solution at different temperatures (288.15, 298.15 and 308.15) K

Physical properties of aqueous solutions of drugs are required to assess the biological activity of that particular drug in treatment of the disease. The most important of the physical parameters are density and speed of sound. From this point of view, we have measured densities and speeds of sound of procaine hydrochloride (Procaine·HCl) in aqueous and in 0.06mol·kg−1 and 0.1mol·kg−1 aqueous solutions of sodium chloride and potassium chloride at three different temperatures i.e. T=(288.15, 298.15 and 308.15)K in the concentration range of (0.01–0.1)mol·kg−1. Density and speed of sound data were used to evaluate different thermodynamic properties such as apparent molar volume (Vϕ) of solute, isentropic compressibility (κs) of solution, apparent molar isentropic compressibility (κϕ) of solute i.e. procaine hydrochloride (Procaine·HCl) in water and in aqueous solutions of 0.06 and 0.1mol·kg−1 sodium chloride and potassium chloride. The limiting apparent molar expansivity (Eϕ0) of procaine hydrochloride and coefficient of thermal expansion (α∗) of procaine hydrochloride have also been estimated. Infinite dilution values of Vϕ and κϕ were also obtained from extrapolation to zero molality and have been utilized in obtaining transfer volumes (ΔtrVϕ0) and transfer compressibilities (Δtrκϕ0) of procaine hydrochloride from water to aqueous solutions of 0.06mol·kg−1 and 0.1mol·kg−1 sodium chloride and potassium chloride at different temperatures. The results are interpreted in terms of different interactions between solute and solvent molecules (solute-solute and solute-solvent interaction).

Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery.

Phospholipid-based deformable nanovesicles (DNVs) that have flexibility in shape offer an adaptable and facile method to encapsulate diverse classes of therapeutics and facilitate localized transdermal delivery while minimizing systemic exposure. Here we report the use of a microfluidic reactor for the synthesis of DNVs and show that alteration of input parameters such as flow speeds as well as molar and flow rate ratios increases entrapment efficiency of drugs and allows fine-tuning of DNV size, elasticity, and surface charge. To determine the ability of DNV-encapsulated drug to be delivered transdermally to a local site, we synthesized, characterized, and tested DNVs carrying the fluorescently labeled hydrophilic bisphosphonate drug AF-647 zoledronate (AF647-Zol). AF647-Zol DNVs were lyophilized, resuspended, and applied topically as a paste to the calvarial skin of mice. High-resolution fluorescent imaging and confocal microscopy revealed significant increase of encapsulated payload delivery to the target tissue—cranial bone—by DNVs as compared to nondeformable nanovesicles (NVs) or aqueous drug solutions. Interestingly, NV delivery was not superior to aqueous drug solution. Our studies show that microfluidic reactor-synthesized DNVs can be produced in good yield, with high encapsulation efficiency, reproducibility, and stability after storage, and represent a useful vehicle for localized transdermal drug delivery.

Molecular dynamics study on DNA nanotubes as drug delivery vehicle for anticancer drugs

In recent years, self-assembled DNA nanotubes have emerged as a type of nano-biomaterials with great potential for biomedical applications. To develop universal nanocarriers for smart and targeted drug delivery from DNA nanotubes, the understanding of interaction mechanism between DNA nanotubes and drugs is essential. In this study, the interactions between anti-cancer drugs and DNA nanotubes were investigated via molecular dynamics simulation. Our simulation results demonstrated that the DNA nanotubes could serve as a good drug delivery material by absorption of anti-cancer drugs with π-π interactions. At high concentration of anti-cancer drugs, most of the drugs could be absorbed by DNA nanotubes. Therefore, it could greatly decrease the aggregation of anti-cancer drugs in aqueous solution. In addition, the stability of DNA nanotubes could be improved with the absorption of anti-cancer drugs. These findings greatly enhance the understanding of the interaction mechanism of DNA nanotubes and anti-cancer drugs. Our study suggests that DNA nanotubes are promising delivery vehicles by strong absorption of anti-cancer drugs.

A reformative shear precipitation procedure for the fabrication of vancomycin-loaded poly(lactide-co-glycolide) microspheres.

This study reports the encapsulation of vancomycin, as a model hydrophilic drug, into poly(lactide-co-glycolide) microspheres using a novel reformative shear precipitation procedure. In contrast to the external aqueous phase used in the conventional microencapsulation technique based on emulsion solvent evaporation/extraction, the reformative shear precipitation procedure explored in this study uses a shear medium composed of glycerol as the viscous medium and ethanol as polymer antisolvent, which is relatively immiscible with the hydrophilic drug. This limits drug diffusion and leads to rapid microsphere solidification, which allows a large proportion of the hydrophilic drug to be encapsulated within the microspheres. The influence of various processing parameters, including polymer concentration, volume ratio of ethanol to glycerol in the shear medium, volume of aqueous drug solution, initial drug loading, and injecting rate of the drug-polymer emulsion, on the encapsulation efficiency and characteristics of resulting microspheres were investigated. The morphology and release characteristics, as well as mechanical, invitro and invivo behaviour of vancomycin-loaded poly(lactide-co-glycolide) microspheres prepared using the novel procedure were also investigated. The results demonstrated that the reformative shear precipitation procedure could achieve the loading of hydrophilic drugs into poly(lactide-co-glycolide) microspheres with high encapsulation efficiency, and the success of the procedure was largely influenced by the volume ratio of ethanol to glycerol in the shear medium. Vancomycin-loaded poly(lactide-co-glycolide) microspheres prepared using this procedure demonstrated favourable mechanical characteristics, antibacterial activity, and invivo degradation behaviour which suggested their suitability for use as a sustained delivery system.

Towards a single bioactive substrate combining SERS-effect and drug release control based on thin anodic porous alumina coated with gold and with lipid bilayers

ABSTRACTThin anodic porous alumina (tAPA), engineered by electrochemical anodization of aluminum and post-fabrication etching, has already shown surface-enhanced Raman scattering (SERS) activity, after overcoating with a thin gold film. On the other hand, the tAPA nanoporous surface, which is biocompatible and presents controlled roughness, has been extensively investigated as a substrate for living cell cultures. Here, we are interested in exploiting the nanoporosity of tAPA as a drug reservoir and demonstrating drug-delivery capabilities of these substrates which can be combined with the above cell-seeding and SERS activities. We focused on the loading/elution of a test drug, the nonsteroidal anti-inflammatory and analgesic molecule Diclofenac. We carried out pore loading of differently concentrated aqueous solutions of the test drug, and characterized the elution profiles by UV-Vis absorbance, using the lipid bilayers coated on the top surface as a mechanism for retarded elution from the pores, providing a more sustained release. We also demonstrated that, by changing an environmental parameter such as the pH, we can trigger an increased release of the drug. Additionally, we investigated the tAPA adsorption properties by quartz crystal microbalance technique with dissipation monitoring (QCM-D). For the purpose, anodization was carried out on an Al-coated quartz, which resulted in successful fabrication of tAPA on the sensor. Finally, the process of lipid bilayer formation on the nanoporous sensor, as well as the test drug loading, was demonstrated by QCM-D.

Solvents of pus-medicines with physical-chemical aggressive action

In laboratory and clinical conditions was studied rheology of pus and sulfuric tubes after their interaction with aqueous solutions of drugs from different pharmacological groups. It is shown that solutions of almost all medicines can influence or not influence on their rheology, because local action is determined not by the name, dose or route of administration of medicines. It is established that only physical-chemical properties of fluids and physical-chemical factors of their interaction with dense pus can give them the ability to dissolve or thickening pus. We found that deliberate change physical-chemical properties of medicines solutions from various pharmacological groups, namely, raising the temperature to +42°C, increasing the alkalinity above pH 8.1 and aeration as for example by introducing carbon dioxide under pressure of 0.2 ATM, or by introducing hydrogen peroxide in 0.5 - 3%, turning them into solvents of pus, ear wax and sulfuric tubes. Discovered that solutions of drugs with such physical-chemical activity may turn thick pus and solid sulfur tube in a homogeneous liquid after a few minutes after injecting them into these biological mass.

Development of Intra-knee Joint Sustained-Release Gel Formulation and Evaluation of Its Pharmacological Efficiency in Rats.

In the development of a drug for intra-articular administration, a sustained-release formulation is desirable since it is difficult to sustain the effects of conventional injections due to fast drug leakage from the joint cavity. In this study, we prepared sustained release gel formulations for intra-articular administration containing indocyanine green (ICG) as a model drug to follow its fate after intra-articular administration in rats with in-vivo imaging system (IVIS). ICG administered as an aqueous solution leaked from the joint cavity in a short time and was excreted out of the body within a day. On the other hand, ICG in the sustained-release formulations was retained and released in the joint cavity for a week. Next, we prepared a sustained-release formulation with hyaluronic acid (HA) as the gel base containing a pain-relief drug (Drug A). We had administered it and other formulations into the rat knee where we injected bradykinin to evaluate their walking distance after 1 and 3 d. The effect of an aqueous solution of Drug A disappeared on day 3. The HA gel formulation without Drug A was more effective than the aqueous solution. The HA gel formulation with Drug A was the most effective; the walking distance was about 85% of the baseline on day 3. This study showed that the gel formulations were effective to sustain the release of a drug in the knee joint, and that the combination of a pain-relief drug with HA gel was effective to improve the mobility of the acute pain model rats.

Optimization of magnetic retention in the gastrointestinal tract: Enhanced bioavailability of poorly permeable drug

Oral administration of low permeable drugs remains a challenge as they do not cross biological membrane efficiently and therefore exhibit a poor bioavailability. Herein, the effect of magnetic retention on the circulation and bioavailability of magnetic beads in the gastrointestinal tract in the presence of an external magnetic field is evaluated. Retention efficiency is imaged using magnetic resonance and near infrared techniques. The effect on bioavailability is then evaluated in a pharmacokinetic study. Iron oxide nanoparticles, the drug (dipeptidyl peptidase-IV inhibitor) and a fluorophore (Alexa Fluor-750) are co-encapsulated in chitosan-alginate core-shell beads. Retention of these beads is induced by the presence of an external permanent magnet on the abdomen of rats. After single administration of magnetic beads containing 20mg/kg of drug to fasted rats, a 2.5-fold increase in drug's bioavailability is observed in the presence of an external magnetic field, significantly higher than the same dose administered to rats without the field or for the drug in aqueous solution. Retention of the magnetic carriers in the presence of an external magnet proves to accumulate these carriers in a specific localization of the intestine leading to a significant improve in the drug's bioavailability.

Development of novel self-assembled ES-PLGA hybrid nanoparticles for improving oral absorption of doxorubicin hydrochloride by P-gp inhibition: In vitro and in vivo evaluation

To increase the encapsulation efficiency and oral absorption of doxorubicin hydrochloride (DOX), a novel drug delivery system of enoxaparin sodium-PLGA hybrid nanoparticles (EPNs) was successfully designed. By introducing the negative polymer of enoxaparin sodium (ES) to form an electrostatic complex with the cationic drug, DOX, the encapsulation efficiency (93.78%) of DOX was significantly improved. The X-ray diffraction (XRD) results revealed that the DOX-ES complex was in an amorphous form. An in vitro release (pH6.8 PBS) study showed the excellent sustained-release characteristics of DOX-loaded EPNs (DOX-EPNs). In addition, in situ intestinal perfusion and intestinal biodistribution experiments demonstrated the improved membrane permeability and intestinal wall bioadhesion of DOX-EPNs, and caveolin- and clathrin-mediated endocytosis pathways were the main mechanisms responsible. The cytotoxicity of DOX was significantly increased by EPNs in Caco-2 cells, compared with DOX-Sol. Confocal laser scanning microscope (CLSM) images confirmed that the amount of DOX-EPNs internalized by Caco-2 cells was higher than that of DOX-Sol showing that P-glycoprotein-mediated drug efflux was reduced by the introduction of EPNs. The qualitative detection of transcytosis demonstrated the ability of the nanoparticles (NPs) to cross Caco-2 cell monolayers. An in vivo toxicity experiment demonstrated that DOX-EPNs reduced cardiac and renal toxic effects and were biocompatible. An in vivo pharmacokinetics study showed that the AUC(0-t) and t1/2 of DOX-EPNs were increased to 3.63–fold and 2.47–fold in comparison with DOX solution (DOX-Sol), respectively. All these results indicated that the novel EPNs were an excellent platform to improve the encapsulation efficiency of an aqueous solution of this antitumor drug and its oral bioavailability.

Volumetric, Viscometric and Spectroscopic Approach to Study the Solvation Behavior of Xanthine Drugs in Aqueous Solutions of NaCl at T = 288.15–318.15 K and at p = 101.325 kPa

The densities (ρ), viscosities (η), and 1H nuclear magnetic resonance (NMR) studies for caffeine, theophylline, and theobromine in water and in aqueous solutions of 0.10, 0.25, 0.50, 0.75, and 1.00 mol·kg–1 sodium chloride over a temperature range T = 288.15–318.15 K and at p = 101.325 kPa have been carried out using vibrating-tube digital densimeter, micro-Ubbelohde type capillary viscometer, and Bruker (AVANCE-III, HD 500 MHz) NMR spectrometer, respectively. From the density and viscosity data, apparent molar volume (V2,ϕ), partial molar volume at infinite dilution (V2,ϕ0), viscosity B-coefficient, corresponding transfer (ΔtrV2,ϕ0 and ΔtrB) and other related parameters have been calculated. The trends in transfer parameters reveal the dominance of hydrophilic–ionic interactions at lower molalities of NaCl while hydrophobic–ionic interactions at higher molalities of NaCl. The expansibilities and dB/dT data show the structure-breaking behavior of theophylline and theobromine in water and in aqueous soluti...