Colloid, interface, and foam properties of water-soluble polyglycerol esters solutions.

HYPOTHESIS: Polyglycerol esters of fatty acids are generated via the esterification of a polydisperse mixture of polyglycerol with naturally derived fatty acids. The polymerization process of polyglycerol results in the production of various oligomers, ranging from di-, tri-, and higher-order forms, which contribute to the complexity of final products. The combination of complementary experimental techniques and adequate theoretical interpretations can reveal the wide variety of their physicochemical properties. EXPERIMENTS: The colloid and interface properties of polyglyceryl mono-laurate, mono-stearate, mono-oleate, and a mixture of mono-caprylate and mono-caprate esters solutions were characterized by measurements of the electrolytic conductivity, static and dynamic surface tension, aggregate and micelle sizes and distributions, thin liquid film stability and stratification, and solubility in aqueous and in oil phases. The formation, stability, and bubble size distribution of foams generated from polyglycerol esters aqueous solutions were systematically investigated. FINDINGS: The low concentrations of double-tail molecules and fatty acids in polyglycerol esters affect considerably their micellar, aggregation, and vesicle formations in aqueous solutions. The theoretical data interpretation of polyglycerol esters isotherms and thin liquid films data provide information on the adsorption energies, excluded areas per molecule, interaction parameters of molecules at interfaces, surface electrostatic potential, and the size of micelles. Polyglyceryl mono-oleate exhibits spontaneous emulsification properties. Short chain length polyglycerol esters have excellent foaming ability but relatively low foam stability. The optimal weight fractions of the short-chain polyglyceryl esters and polyglyceryl mono-stearate mixtures with respect to good foaminess and foam stability upon Ostwald ripening are obtained. The reported physicochemical characterization of the water-soluble polyglycerol esters could be of interest to increase the range of their applicability in practice.

Spectroscopic and Thermal Characterisation of Interpenetrating Hydrogel Networks (IHNs) Based on Polymethacrylates and Pluronics, and Their Physicochemical Stability under Aqueous Conditions.

This study describes the physicochemical characterisation of interpenetrating hydrogel networks (IHNs) composed of either poly(hydroxyethylmethacrylate, p(HEMA)) or poly(methacrylic acid, p(MAA)), and Pluronic block copolymers (grades F127, P123 and L121). IHNs were prepared by mixing the acrylate monomer with Pluronic block copolymers followed by free radical polymerisation. p(HEMA)-Pluronic blends were immiscible, evident from a lack of interaction between the two components (Raman spectroscopy) and the presence of the glass transitions (differential scanning calorimetry, DSC) of the two components. Conversely, IHNs of p(MAA) and each Pluronic were miscible, displaying a single glass transition and secondary bonding between the carbonyl group of p(MAA) and the ether groups in the Pluronic block copolymers (Raman and ATR-FTIR spectroscopy). The effect of storage of the IHNs in Tris buffer on the physical state of each Pluronic and on the loss of Pluronic from the IHNs were studied using DSC and gravimetric analysis, respectively. Pluronic loss from the IHNs was dependent on the grade of Pluronic, time of immersion in Tris buffer, and the nature of the IHN (p(HEMA) or p(MAA)). At equilibrium, the loss was greater from p(HEMA) than from p(MAA) IHNs, whereas increasing ratio of poly(propylene oxide) to poly(ethylene oxide) decreased Pluronic loss. The retention of each Pluronic grade was shown to be primarily due to its micellization; however, hydrogen bonding between Pluronic and p(MAA) (but not p(HEMA)) IHNs contributed to their retention.

Effects of side-chain lengths on the structure and properties of anhydrides modified starch micelles: Experimental and DPD simulation studies.

Anhydride-modified starch micelles have great potential in the delivery of hydrophobic guest molecules. This study aimed to experimentally explore the effects of side-chain lengths on the structure and properties of anhydride-modified starch micelles, and to visualize the self-assembly and loading process of these micelles through Dissipative particle dynamics (DPD) simulations. Starch micelles could only form when the carbon chain length exceeded four. The highly hydrophobic C18 starch micelle exhibited the minimum particle size (65 nm) and maximum loading capability (59.10 µg/mg). For each addition carbon atom in the anhydride side chains, the critical micelle concentration (CMC) of starch micelles decreased average of 1.79 %. Thermodynamic results showed that the micellization was an entropy-dominated driven process, and longer carbon chains enhanced the stability of starch micelles. DPD results showed that the starch chains formed the small clusters then spherical aggregates and finally core-shell structure spherical micelle. Curcumin was loaded into micelles by adjoint aggregation-micellization-adsorption mechanism. Overall, this study provides microscopic insight into the micellization and drug-loading mechanisms for anhydrides modified starch micelles.

Emulsions vs excipient emulsions as α-tocopherol delivery systems: Formulation optimization and behaviour under in vitro digestion.

Oil-in-water emulsions (EM) have been extensively used for the encapsulation of lipophilic bioactive compounds and posterior incorporation into food matrices to obtain functional foods. Conversely, novel excipient oil-in-water emulsions (EXC) present identical composition and structure as EM, albeit are not bioactive by themselves since no bioactive compound is encapsulated. Instead, EXC aims at improving the bioavailability of foods' natural bioactive compounds upon co-ingestion with nutrient-rich foods. In this work, EM and EXC were produced and their stability and functionality as delivery systems for α-tocopherol compared. Emulsions were formulated with corn oil and lecithin, and their composition was optimized using experimental designs. Formulations produced with 3 % lecithin and 5 % oil attained smallest particles sizes with the lowest polydispersity index of all tested formulations and remained stable up to 60 days. Encapsulation of α-tocopherol did not have a significative impact on the structural properties of the particles produced with the same composition. α-tocopherol stability during in vitro digestion was superior in EM regardless the processing methodology (EM stability < 50 %, EXC stability < 29 %), indicating that EM offered greater protection against the digestive environment. α-tocopherol's bioaccessibility was significantly increased when encapsulated or when digested with added excipient emulsions (82-92 % and 87-90 % for EM and EXC, respectively). In conclusion, EM were more efficient vehicles for the selected bioactive compound, however, the good results obtained with EXC imply that excipient emulsions have a great potential for applications on foods to improve their natural bioactive compounds' bioavailability without the need of further processing.

Low ß-carotene bioaccessibility and bioavailability from high fat, dairy-based meal.

PURPOSE: The original aim of the study was to determine, in a double-blind 3-arm crossover human trial (n = 7), the effect of supplemental levels of iron (25 mg) and zinc (30 mg) on ß-carotene (synthetic) bioavailability (10 h postprandial). However, despite the high dose of supplemental ß-carotene (15 mg) consumed with the high fat (18 g), dairy-based breakfast test meal, there was a negligible postprandial response in plasma and triglyceride rich fraction ß-carotene concentrations. We then systematically investigated the possible reasons for this low bioavailability of ß-carotene. METHODS: We determined (1) if the supplemental ß-carotene could be micellised and absorbed by epithelial cells, using a Caco-2 cell model, (2) if the fat from the test meal was sufficiently bioavailable to facilitate ß-carotene bioavailability, (3) the extent to which the ß-carotene could have been metabolised and converted to retinoic acid/retinol and (4) the effect of the test meal matrix on the ß-carotene bioaccessibility (in vitro digestion) and Caco-2 cellular uptake. RESULTS: We found that (1) The supplemental ß-carotene could be micellised and absorbed by epithelial cells, (2) the postprandial plasma triacylglycerol response was substantial (approximately 75-100 mg dL-1 over 10 h), indicating sufficient lipid bioavailability to ensure ß-carotene absorption, (3) the high fat content of the meal (approximately 18 g) could have resulted in increased ß-carotene metabolism, (4) ß-carotene bioaccessibility from the dairy-based test meal was sixfold lower (p < 0.05) than when digested with olive oil. CONCLUSION: The low ß-carotene bioavailability is probably due to a combination of the metabolism of ß-carotene to retinol by BCMO1 and interactions of ß-carotene with the food matrix, decreasing the bioaccessibility. TRAIL REGISTRATION: The human trail was retrospectively registered (ClinicalTrail.gov ID: NCT05840848).

Destabilization of a model O/W/O double emulsion: From bulk to interface.

Oil-in-water-in-oil (O/W/O) double emulsions are considered an advanced oil-structuring technology that can accomplish multi-functions to improve food quality and nutrition. However, this special structure is thermodynamically unstable. This study formulated a model O/W/O double emulsion with standard surfactants, Tween 80 (4 %) and polyglycerol polyricinoleate (PGPR, 5 %), using a traditional two-step method with different homogenization parameters. Cryo-SEM and GC-FID results show that O/W/O emulsions were successfully formulated, and the release rate (RR) of medium-chain triglycerides (MCT) oil from the inner oil to the outer oil phase increased significantly with 2nd homogenization speed increasing, respectively. Interestingly, the RR of all samples reached about 75 % after 2 months of storage, suggesting that O/W/O emulsions were highly unstable. To explain the observed instability, dynamic interfacial tension and interfacial rheology were performed using a drop shape tensiometer. Results demonstrated that unadsorbed Tween 80 in the intermediate aqueous phase was a key factor in markedly decreasing the interfacial properties of the outer PGPR-assembled film by affecting the interfacial rearrangement. Additionally, it was found that the MCT release showed a positive correlation with the Tween 80 concentration, demonstrating that the formed Tween 80 micelles could transport oil molecules to strengthen the emulsion instability. Taken together, this study reveals the destabilization mechanism of model O/W/O surfactants-stabilized emulsions from bulk to interface, providing highly relevant insights for the design of stable O/W/O double emulsions.

Adsorption Properties and Wettability of Ethoxy- and Propoxy- Derivatives of 2-Ethylhexanol as Sterically Specific Surfactant Structures.

2-ethylhexanol, an oxo alcohol competitively priced on the global market, has not been explored intensively as a raw material for surfactants, due to its weak hydrophobic character. However, its sequenced propoxylation and ethoxylation yield an innovative amphiphilic structure, which exhibits unique interfacial activity. The paper presents the differences in the fractional composition of innovative surfactants derived from 2-EH alcohol prepared using alkali and dimetalcyanide catalysts, as well as examples of excellent adsorption and interfacial properties of the latter. The adsorption behavior of the synthesized compounds was explored using equilibrium surface tension (the du Noüy ring method), dynamic surface tension (the maximum gas bubble pressure method) and static/dynamic contact angle (the sessile drop method). The results from the adsorption tests conducted at the air/aqueous surfactant solution interface underwent comprehensive qualitative and quantitative analyses. Moreover, based on the experimentally obtained dynamic surface tension isotherms and the developed algorithm, the diffusion coefficients for these preparations were estimated, and it was shown that the diffusivity of these surfactants is higher compared to the commercial formulations. The study's outcomes in the testing of wettability indicate that new synthesized nonionic and anionic surfactants constitute an interesting group of amphiphiles with a wide application potential as effective wetting agents, especially in relation to the polymer surface. It should therefore be emphasized that the innovative surfactants described in this article, derived from 2-EH alcohol and prepared using dimetalcyanide catalysts, can successfully compete with conventional preparations such as ABS (Dodecylbenzenesulfonic Acid) or AES (Alcohol Ethoxysulphate) acid salts.

Piperidinium surfactants functionalized with carbamate fragment: Aggregation, antimicrobial activity and cytotoxicity.

The biomimetic nature of supramolecular systems, the structural similarity of synthetic surfactants to biomolecules (lipids, proteins), provide them with high membranotropy, the ability to overcome biological barriers, and affinity towards biosubstances. Despite rather high toxicity cationic surfactants are of importance as antimicrobial agents, gene nanocarriers and mitochondria targeted ligands. To minimize this limitation, cationic amphiphilic matrix undergoes modification with various functional groups. In this work, new piperidinium cationic surfactants containing one or two carbamate fragments were prepared; their aggregation behavior was systematically studied by tensiometery, spectrophotometry and fluorimetry. The presence of a carbamate fragment leads to a 2-3-fold decrease in critical micelle concentration and to a significant increase in solubilization capacity compared to unsubstituted analogue. Evaluation of the antimicrobial effect showed that all compounds exhibit high bactericidal and fungicidal activity against a wide range of pathogenic microorganisms, including their resistant forms. Importantly, the introducing carbamate moiety allows of decreasing hemolytic activity of cationic surfactants. The data obtained make it possible to recommend carbamate piperidinium surfactants as effective biocompatible and biodegradable nanocontainers for hydrophobic probes with high antimicrobial effect and moderate hemolytic activity.

Aggregation phenomena and physico-chemical properties of tetradecyltrimethylammonium bromide and protein (bovine serum albumin) mixture: Influence of electrolytes and temperature.

It is important for biological, pharmaceutical, and cosmetic industries to understand how proteins and surfactants interact. Herein, the interaction of bovine serum albumin (BSA) with tetradecyltrimethylammonium bromide (TTAB) in different inorganic salts (KCl, K2SO4, K3PO4.H2O) has been explored through the conductivity measurement method at different temperatures (300.55 to 325.55 K) with a specific salt concentration and at a fixed temperature (310.55 K) using different salts concentrations. The extent of micelle ionization (α) and different thermodynamic parameters associated with BSA and TTAB mixtures in salt solutions were calculated. Evaluation of the magnitudes of ∆Hm0 and ∆Sm0 showed that the association was exothermic and primarily an enthalpy-operated process in all cases at lower contents of BSA, but the system became endothermic, and entropy driven in the presence of K3PO4.H2O at a relatively higher concentration of BSA. The enthalpy-entropy compensation variables were determined, which explained the types and nature of interactions between TTAB and BSA in salt media. Molecular docking analysis revealed that the main stabilizing factors in the BSA-TTAB complex are electrostatic and hydrophobic interactions. These findings aligned with the significant results obtained from the conductometry method regarding the nature and characteristics of binding forces observed between BSA and TTAB.

Effect of antidiabetic drug metformin hydrochloride on micellization behavior of cetylpyridinium bromide in aqueous solution.

Herein, the interaction of an antidiabetic drug, metformin hydrochloride (MHCl), and a cationic surfactant, cetylpyridinium bromide (CPB) is investigated in an aqueous medium. The critical micellar concentration (CMC) of CPB is estimated through conductivity experiments and found to be reduced on adding MHCl and further decreased in the presence of NaCl. The reduced CMC is attributed to the solubilization of MHCl by CPB through micellization and the micellization is found to be thermodynamically spontaneous that experiences an augmentation in the presence of NaCl. This is identified from the negative value of standard free energy (ΔG0m). The higher negative value of ΔG0m (-55.41 kJ mol-1) for CPB + MHCl + NaCl than CPB (-37.89 kJ mol-1) and CPB + MHCl (-34.08 kJ mol-1) is suggestive of the above phenomenon. The positive values of ΔS0m in all three cases confirm that the micellization is entropy driven. The binding of MHCl on CPB is quantified by estimating binding constant using the Benesi-Hildebrand (B-H) plot through UV-visible spectral methods. The binding constant values were calculated to be 2.70 M-1 for CPB + MHCl + NaCl compared to 1.258 M-1 for CPB + MHCl predicting a favoring of micellization in the presence of NaCl which is higher than that in the presence of co-solvents. The molecular interaction of MHCl and CPB is justified using FT-IR and NMR techniques. The surface properties of drug surfactant interactions are assessed using SEM techniques. The point of interaction between the drug and surfactant is visualized through the molecular docking approach. The results suggest that CPB would be an effective solubilizer for developing MHCl drug formulations.Communicated by Ramaswamy H. Sarma.

RNA-Seq analysis of the pyloric caecum, liver, and muscle reveals molecular mechanisms regulating fillet color in rainbow trout.

BACKGROUND: The characteristic pink-reddish color in the salmonids fillet is an important, appealing quality trait for consumers and producers. The color results from diet supplementation with carotenoids, which accounts for up to 20-30% of the feed cost. Pigment retention in the muscle is a highly variable phenotype. In this study, we aimed to understand the molecular basis for the variation in fillet color when rainbow trout (Oncorhynchus mykiss) fish families were fed an Astaxanthin-supplemented diet. We used RNA-Seq to study the transcriptome profile in the pyloric caecum, liver, and muscle from fish families with pink-reddish fillet coloration (red) versus those with lighter pale coloration (white). RESULTS: More DEGs were identified in the muscle (5,148) and liver (3,180) than in the pyloric caecum (272). Genes involved in lipid/carotenoid metabolism and transport, ribosomal activities, mitochondrial functions, and stress homeostasis were uniquely enriched in the muscle and liver. For instance, the two beta carotene genes (BCO1 and BCO2) were significantly under-represented in the muscle of the red fillet group favoring more carotenoid retention. Enriched genes in the pyloric caecum were involved in intestinal absorption and transport of carotenoids and lipids. In addition, the analysis revealed the modulation of several genes with immune functions in the pyloric caecum, liver, and muscle. CONCLUSION: The results from this study deepen our understanding of carotenoid dynamics in rainbow trout and can guide us on strategies to improve Astaxanthin retention in the rainbow trout fillet.

Physicochemical and chemical properties of mung bean protein isolate affected by the isolation procedure.

The effects of different mung bean protein isolation methods on the chemical composition, the physicochemical properties, and selected antinutritional factors of mung bean protein isolates were investigated. Six protein isolates were prepared by isoelectric precipitation at different extraction pH levels (pH 8 and 9), by micellization, and by hybrid isolation at varying salt concentrations (0.25 M, 0.50 M, 0.75 M). The extraction conditions affected the amount of antinutritive compounds of the isolates. Compared to mung bean flour, micellization reduced phytic acid content by approximately 48% and trypsin inhibitor activity by around 88%. The remaining phytic acid concentration of the isolates influenced their re-solubility, particularly under acidic conditions. The protein isolates exhibited significant differences in surface hydrophobicity and thermal characteristics, indicating structural modifications caused by the extraction methods. Micellization and extraction at pH 8 were identified as mildest isolation methods, as evidenced by the highest enthalpy values. SDS-PAGE analysis demonstrated an enrichment of globulins and comparable protein profiles among the isolates, suggesting that the observed differences arise from conformational changes rather than variations in protein composition. The product yield in protein extraction from mung beans ranged from 8% to 19%, emphasizing the importance of enhancing overall extraction efficiency or exploring the utilization of by-products obtained during the protein isolation process.

Electrochemical behavior, antimicrobial activities, and effect of temperature on micellization of imidazolium monomeric surfactants.

In the present study, we herein report the conductance behavior, effect of temperature, and chain-length of two environmentally friendly imidazolium cationic capric and stearic surfactants. The conductance behavior has been carried out in aqueous solvent (H2O) at four different temperatures such as 24 °C, 29 °C, 34 °C, and 39 °C. The normal micelles were formed in an aqueous solvent and critical micelle concentration (CMC) can be estimated through conductivity parameters. The expected dependency of the CMC on the alkyl chain length of the 3-(2-(decanoyloxy)ethyl)-1-methyl-1H-imidazol-3-ium-bromide and 3-(2-(octadecanoyloxy)ethyl)-1-methyl-1H-imidazol-3-ium-bromide was demonstrated. It was observed that the graphs of molar conduct activity v/s square root were not linear, which specifies that the synthesized surfactants behave as weak electrolytes in the dilute solutions. The electrochemical characterization of capric and stearic surfactant modified SPCE was studied in 1mM K3FeCN6 solution. The CS/SPCE and SS/SPCE were shown elevated sensitivity, high stability, and excellent conductivity. Moreover, the antimicrobial behaviors of the synthesized imidazolium cationic surfactants versus various microbial strains were evaluated. Results showed that capric surfactant demonstrated high antibacterial activity against Escherichia coli (MIC > 31.5 µg/mL).

Role of Bovine Serum Albumin Addition in Micellization and Gel Formation of Poloxamer 407.

The combination of the thermoresponsive polymer and protein has demonstrated great promise in its applications in drug delivery and tissue engineering fields. This study described the impact of bovine serum albumin (BSA) on the micellization and sol-gel transition behaviors of poloxamer 407 (PX). The micellization of aqueous PX solutions with and without BSA was examined using isothermal titration calorimetry. In the calorimetric titration curves, the pre-micellar region, the transition concentration region, and the post-micellar region were observed. The presence of BSA had no noticeable impact on critical micellization concentration, but the inclusion of BSA caused the pre-micellar region to expand. In addition to studying the self-organization of PX at a particular temperature, the temperature-induced micellization and gelation of PX were also explored using differential scanning calorimetry and rheology. The incorporation of BSA had no discernible effect on critical micellization temperature (CMT), but it did affect gelation temperature (Tgel) and gel integrity of PX-based systems. The response surface approach illustrated the linear relation between the compositions and the CMT. The major factor affecting the CMT of the mixtures was the concentration of PX. The alteration of the Tgel and the gel integrity were discovered to be a consequence of the intricate interaction between PX and BSA. BSA mitigated the inter-micellar entanglements. Hence, the addition of BSA demonstrated a modulating influence on Tgel and a softening effect on gel integrity. Understanding the influence of serum albumin on the self-assembly and gelation of PX will enable the creation of thermoresponsive drug delivery and tissue engineering systems with controlled gelation temperatures and gel strength.

Thermodynamic Parameters of Berberine with Kolliphor Mixtures Adsorption and Micellization.

The poor solubility of berberine (Ber) in water limits its practical use. Its solubility can be increased, among other ways, by the addition of surfactants. Of the surfactants, Kolliphor® ELP (ELP) and Kolliphor® RH 40 (RH40) can be very useful in this respect. The increase of Ber's solubility in water in the presence of ELP and RH40 should be reflected in the composition of the surface layers at the water-air interface and the micelles. The determined composition is reflected in the Gibbs energy of interactions of berberine with ELP and RH40 through the water phase and the standard Gibbs free energy, enthalpy, and entropy of adsorption and micellization. These energies were determined from the equations proposed by us, based on the Gibbs surface excess concentration of the Ber mixture with ELP and RH40, the activity of these compounds in the surface layer at the water-air interface and in the micelles obtained by the Hua and Rosen method, and the contributions of Ber, ELP, and RH40 to the reduction in the water surface tension. For this determination, the measurements of the surface tension of the aqueous solution of the Ber mixture with ELP or RH40 and that of the Ber mixture with these two surfactants, as well as the density and conductivity were performed. Moreover, the fluorescence emission spectra for the Ber + surfactant mixtures were recorded.

Rhamnolipid Self-Aggregation in Aqueous Media: A Long Journey toward the Definition of Structure-Property Relationships.

The need to protect human and environmental health and avoid the widespread use of substances obtained from nonrenewable sources is steering research toward the discovery and development of new molecules characterized by high biocompatibility and biodegradability. Due to their very widespread use, a class of substances for which this need is particularly urgent is that of surfactants. In this respect, an attractive and promising alternative to commonly used synthetic surfactants is represented by so-called biosurfactants, amphiphiles naturally derived from microorganisms. One of the best-known families of biosurfactants is that of rhamnolipids, which are glycolipids with a headgroup formed by one or two rhamnose units. Great scientific and technological effort has been devoted to optimization of their production processes, as well as their physicochemical characterization. However, a conclusive structure-function relationship is far from being defined. In this review, we aim to move a step forward in this direction, by presenting a comprehensive and unified discussion of physicochemical properties of rhamnolipids as a function of solution conditions and rhamnolipid structure. We also discuss still unresolved issues that deserve further investigation in the future, to allow the replacement of conventional surfactants with rhamnolipids.

Adsorption and volumetric properties of some nonionic surfactants and their mixtures with quercetin and rutin.

The adsorption and volumetric properties of the Triton X-114 (TX114), Tween 80 (T80), quercetin (Q) and rutin (Ru) at the different temperatures in relation to above properties of the TX114 and T80 mixtures with quercetin and rutin in the absence and presence of alcohol were discussed based on the studies reported in the literature. The adsorption isotherms of the mixtures of the nonionic surfactants with flavonoids in the presence and absence of alcohol were analyzed based on the isotherms of the surface tension of the particular mixture components and thermodynamic parameters of the adsorption of these components at the water-air interface. The surface tension isotherms of the particular component of the mixtures were taken into account while considering the surface tension isotherms of the mixtures and the composition of the mixed surface layer at the water-air interface. Different ways of the mixed surface layer composition determination were shown. The values of the surface tension and composition of the mixed surface layers obtained using different methods were discussed in the light of the intermolecular interactions and their contribution to the surface tension of the surfactants mixture with flavonoids and alcohol. The composition of the mixed monolayer and the bulk phase were compared and the differences between them were explained. The behaviour of the nonionic surfactants and flavonoids in the presence and absence of alcohol was analyzed in relation to the micelle formations and molar volumes of the mixtures and their components. Moreover, the micelles composition and their size as well as the thermodynamic parameters of the micellization process were analyzed.

Enhancing Oil Solubility of BCS Class II Drug Phenytoin Through Hydrophobic Ion Pairing to Enable High Drug Load in Injectable Nanoemulsion to Prevent Precipitation at Physiological pH With a Potential to Prevent Phlebitis.

This work investigates the micellar titration of phenytoin (a weakly acidic drug) with cetyltrimethylammonium hydroxide (CTAH) to form a hydrophobic ion-pair to enhance oil solubility of phenytoin, followed by an effort to formulate nanoemulsion that could potentially prevent precipitation of phenytoin at physiological pH. The ion-pair formulated in nanoemulsion was evaluated for in vitro precipitation during serial dilution at physiological pH. The formation of ion-pair during titration was explained in context of pH-solubility data. The mathematical model successfully integrated ionization and micellization equilibria to reflect on dominant mechanisms for solubilization. The micellar phenomenon during titration was confirmed using Dynamic Light Scattering (DLS). The phase changes of the excess undissolved solids during titration were evident from X-Ray Powder Diffraction (XRPD) and Fourier Transform Infrared Spectroscopy (FTIR). This analysis confirmed the conversion of phenytoin into ionized state and its subsequent ionic interaction with CTAH forming hydrophobic ion-pair complex (HIP). The complete ion pair formation was evident at pHmax (8.8 to 9.2), and its 1:1 stoichiometry was confirmed using HPLC (Phenytoin and CTAH) and H1 NMR, hence could also be called as a lipophilic salt. The ion-pair (salt) was insoluble in water and showed remarkably high partition coefficient (log P) in octanol/water. As characterized by Hot Stage Microscopy (HSM), the melting point of the ion-pair complex was lowered to 150.8°C compared to the free acid (> 300οC), this was even further lowered to 81.1 °C when evaluated in castor oil. This led to approximately eight-fold higher solubility of hydrophobic ion pair (HIP) in castor oil compared to the free acid form. The high miscibility in castor oil was suitable to formulate a high drug load injectable dispersed system. This was successfully achieved with lecithin and polysorbate as emulsifiers without leaching drug into continuous phase at pH 7.4. This nanoemulsion (<300 nm, and > +30 mV zeta potential) remain stable when evaluated over a period of one month. A serial dilution study of the nanoemulsion was performed in PBS buffer, microscopic observations suggested no birefringence despite incubation at 25°C for several hours. This result indicated that Phenytoin remained strongly partitioned within dispersed oily phase with a higher drug loading when ion-paired phenytoin was used. The higher drug load could enable a small volume slow bolus injection to meet 50 mg/min or lower delivery rate criteria for Phenytoin in the clinical set up. This provided a pathway to further explore potential injectable nano-emulsion formulations that could alleviate typical phlebitis issue associated with the injectable phenytoin solution administration at physiological pH.

Phase behavior of medium-length hydrophobically associating PEO-PPO multiblock copolymers in aqueous media.

HYPOTHESIS: The micellization of block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) is driven by the dehydration of PPO at elevated temperatures. At low concentrations, a viscous solution of isolated micelles is obtained, whereas at higher concentrations, crowding of micelles results in an elastic gel. Alternating PEO-PPO multiblock copolymers are expected to exhibit different phase behavior, with altered phase boundaries and thermodynamics, as compared to PEO-PPO-PEO triblock copolymers (Pluronics®) with equal hydrophobicity, thereby proving the pivotal role of copolymer architecture and molecular weight. EXPERIMENTS: Multiple characterization techniques were used to map the phase behavior as a function of temperature and concentration of PEO-PPO multiblock copolymers (ExpertGel®) in aqueous solution. These techniques include shear rheology, differential and adiabatic scanning calorimetry, isothermal titration calorimetry and light transmittance. The micellar size and topology were studied by dynamic light scattering. FINDINGS: Multiblocks have lower transition temperatures and higher thermodynamic driving forces for micellization as compared to triblocks due to the presence of more than one PPO block per chain. With increasing concentration, the multiblock copolymers in solution gradually evolve into a viscoelastic network formed by soluble bridges in between micellar nodes, whereas hairy triblock micelles jam into liquid crystalline phases resembling an elastic colloidal crystal.

Physicochemical approaches reveal the impact of electrolytes and hydrotropic salt on micellization and phase separation behavior of polymer polyvinyl alcohol and surfactant mixture.

The polymer-surfactant mixture has usages in numerous industries mainly in the production of daily used materials. Herein, the micellization and phase separation nature of the sodium dodecyl sulfate (SDS) and TX-100 along with a synthetic water-soluble polymer-polyvinyl alcohol (PVA) have been conducted using conductivity and cloud point (CP) measurement tools. In the case of micellization study of SDS + PVA mixture by conductivity method, the CMC values were obtained to be dependent on the categories and extent of additives as well as temperature variation. Both categories of studies were performed in aq. solutions of sodium chloride (NaCl), sodium acetate (NaOAc), and sodium benzoate (NaBenz) media. The CP values of TX 100 + PVA were decreased and enhanced in simple electrolytes and sodium benzoate media respectively. In all cases, the free energy changes of micellization (∆Gm0) and clouding (∆Gc0) were obtained as negative and positive respectively. The enthalpy (∆Hm0) and entropy (∆Sm0) changes for SDS + PVA system micellization was negative and positive respectively in aq. NaCl and NaBenz media, and in aq. NaOAc medium the ∆Hm0 values were found negative while ∆Sm0 were found negative except at the highest studied temperature (323.15 K). The enthalpy-entropy compensation of both processes was also assessed and described clearly.