Anionic Hydrotropes Research Articles

Physico-chemical investigation of the assembly and clouding development nature of the mixture of metformin hydrochloride and ionic/nonionic surfactants: Influences of hydrotropes

The clouding development and the association of the mixture of surfactant and antidiabetic drug metformin hydrochloride (MNH) have been investigated in aq. solutions of two anionic hydrotropes (sodium salicylate (NaSal) and sodium benzoate (NaBenz)) and an uncharged hydrotrope (4-amino benzoic acid (4-ABA)) (HDTs) media. In the present study, nonionic (triton X-100 (TX-100)) and cationic (tetradecyltrimethylammonium bromide (TTAB)) surfactants were employed. The cloud point (CP) of TX-100 + MNH system has been reduced with the enhancing contents of HDTs. The micellar variables (critical micelle concentration (CMC) and extent of ionization (α) of TTAB + MNH system have been assessed while the parameters are dependent on the HDT contents and changes of study temperature. The free energy of clouding (ΔGc0) and assembly (ΔGc0) processes have been detected as positive and negative respectively which indicated that the respective processes are non-spontaneous and spontaneous in nature. For the clouding and assembly processes, the standard enthalpy (ΔHc0/ΔHm0), and standard entropy (ΔSc0/ΔSm0) were also determined and discussed. The ΔHc0 and ΔSc0 recommend that the core forces between TX-100 and MNH in presence of 4-ABA are H-bonding and electrostatic interactions but hydrophobic interaction is suggested as main force amid the employed components in aq. NaBenz and NaSal media. The ΔHm0 and ΔSm0 values of TTAB + MNH assembly reveal the occurrence of electrostatic interaction and hydrophobic forces amid the components inspected.

Influence of an anionic hydrotrope on thermophysical properties of an anionic surfactant sodium dodecyl sulfate

Herein we report micellization behavior of anionic surfactant, sodium dodecyl sulfate (SDS) in presence and absence of anionic hydrotrope (1,3-Benzenedisulfonic acid disodium salt (BDS)) in aqueous medium. Critical micelle concentrations (CMC) of mixed surfactant-hydrotrope systems were determined by conductometric technique. CMC values of surfactant-hydrotrope decrease with increasing hydrotrope concentration. Interactions between hydrotrope and surfactant are synergistic in nature. We also deduced thermodynamic parameters of micellization (viz., ΔG°m, ΔH°m, and ΔS°m). The effect of hydrotrope and temperature on different thermophysical properties have been discussed. Experimental techniques like FT-IR and NMR were employed to reveal the non-covalent interactions of mixed surfactant-hydrotrope systems.

Interactions between promethazine hydrochloride drug and sodium benzoate hydrotrope mixtures in various solvent media at different temperatures

The current study investigated the mixed micellization of a phenothiazine drug, promethazine hydrochloride (PMT), with the anionic hydrotrope sodium benzoate (NaB) using a conductometric method in three different solvent media: water, 50 mmol.kg−1 sodium chloride (NaCl), and 300 mmol.kg−1 urea (U). Five different temperatures, ranging from 293.15 to 313.15 K, were chosen for the current study of both pure and mixed systems. PMT belongs to a class of drugs known as antihistamines, which are used to treat allergy symptoms. Various physicochemical parameters of both pure and mixed systems (PMT+NaB) were evaluated at different compositions and temperatures, using numerous theoretical models associated with mixed micellization. The attained critical micelle concentration (cmc) and ideal cmc (cmcid) values indicated the formation of mixed micelles due to interactions between the components. The evaluated cmc value for PMT, the minimum hydrotropic concentration (mhc) of NaB, and the cmc value for the PMT+NaB mixture decreased in the NaCl system and increased in the U system compared with these values in the aqueous solution. The cmc values of the studied mixed systems decrease due to an upsurge in the mole fraction (α1) of NaB, indicating the non-ideality of the evaluated solution mixtures. The interaction parameter (β) was negative, revealing that the interaction between the constituents increased with the increasing α1 of NaB in aqueous solution. In the NaCl solution, the β value increased, whereas, in the U solution, the value decreased. The degree of dissociation (g) values decreased by increasing the α1 of NaB in the solution mixture. Various thermodynamic parameters were also evaluated in detail. The activity coefficient values in all cases were below unity, which further indicated the non-ideality of the system. The assessed excess free energy (∆GexRb) of the system was found to be negative in all cases, displaying the stability of the formed mixed micelles. Across the different solvents, their magnitudes were observed in the following order: ∆GexRb in NaCl > ∆GexRb in water >∆GexRb in U. An ultraviolet (UV)-visible study showed a clear interaction between NaB and PMT in the aqueous system. A Fourier-transform-infrared (FT-IR) spectroscopy investigation revealed a shift in the frequency bands of the components due to the interactions between them.

Association behavior of the amphiphilic drug and sodium p-toluenesulfonate mixtures: Effect of additives

The interaction between an amphiphilic phenothiazine drug—promethazine hydrochloride (PMT)—and anionic hydrotrope sodium p-toluenesulfonate (NaTS) mixtures was analyzed and the effect of different mole fractions (α1) of NaTS along with the variation of temperature was also investigated in three different media, water/NaCl (50 mmol.kg−1)/urea (U) (300 mmol.kg−1), using a conductometric method. Drug PMT is mainly utilized to cure allergic symptoms. From the study of pure components along with solution mixtures of components, various physicochemical parameters were evaluated and discussed thoroughly. The obtained results show that the experimental critical micelle concentrations (cmcs) are less than their corresponding ideal cmc (cmcid) values, showing the interaction amongst the constituents (PMT and NaTS). Mixing of dissimilar kinds of amphiphiles has an opportunity to bring about additional valuable acts owing to their attractive interaction. As hydrophobicity of the PMT + NaTS mixtures increased, therefore the cmc values remarkably decreased. The degree of dissociation (g) of the studied system was also evaluated and found to increase with a rise in temperature and decrease via an increase in α1 of NaTS. In salt (NaCl) solution, cmc and g-value of PMT and PMT+ NaTS at all compositions were decreased compared with an aqueous system while in U solution their value was found to be greater than in aqueous solution. Various theoretical models were also considered to estimate the fraction of hydrotrope in mixed micelles PMT + NaTS, the parameter is named the micellar mole fraction (X1Rb (Rubingh model), X1Rd (Rodenas model) and their ideal value is X1id), and the obtained value shows the higher composition of NaTS in mixed micelles along with their value increasing through an increase of α1 of NaTS in the solution mixture. One other parameter, called the interaction parameter (β), was observed as negative throughout the study, also proving the attractive interaction/synergism amongst the components of the solution mixture (PMT + NaTS). Assessed activity coefficients were all below one, showing the nonideality of the studied system. Several thermodynamic parameters of micellization, such as Gibbs free energy (ΔGm0), enthalpy (ΔHm0), and entropy (ΔSm0) have been determined in all studied media and compositions. UV–visible spectroscopy also confirmed the interaction amongst PMT and NaTS. Scanning electron microscope (SEM) images depicted a clear-cut interaction of PMT and NaTS interaction. The outcomes from the current study are significant in the expansion of the operative model drug delivery process.

Pre-nucleation cluster formation upon ethyl acetate addition to an aqueous solution of an anionic hydrotrope

Hydrotropes are used to solubilize poorly soluble solutes. Here the general features of the solution behaviour of the very common anionic hydrotrope sodium salicylate is investigated. With the use of density and scattering measurements, it is demonstrated that around the critical point neither pre-Ouzo structuring nor an Ouzo effect are present. By contrast, in a domain near the liquid-solid phase boundary, X-ray light and neutron scattering combined with a density excess determination prove the presence of dynamic aggregates. These aggregates are stabilized without any surfactants, but by selective solvation of ethyl acetate, reminiscent of stable liquid pre-nucleation aggregates. And most surprising: in water saturated by ethyl acetate (20% wt), sodium salicylate micellizes like a medium chain classical surfactant.

Effect of additives on the aggregation phenomena of amphiphilic drug and hydrotrope mixtures

Association behavior between the cationic antidepressant drug imipramine hydrochloride (IPH) and anionic hydrotrope - sodium benzoate (NaBez) mixtures in aqueous solutions, along with the electrolytes NaCl (50 mmol·kg−1) and NaBr (50 mmol·kg−1) were studied using a conductometric technique at four different temperatures. The results showed a decrease in critical micelle concentration (cmc) of IPH (drug) in combination with NaBez, viewing a remarkable interaction amongst studied constituents along with cmc values of IPH drug further lessens through raised in mole fraction (α1) of NaBez. The electrolytes NaCl and NaBr reduced the cmc of IPH, NaBez together with their mixture (IPH-NaBez) in diverse ratio and NaBr was additionally effectual in reducing the cmc of the system in comparison to NaCl. Moreover, the cmc values of IPH and NaBez mixtures showed a lower than ideal cmc (cmcid) value characterizing the non-ideality in system. Additional parameters of the conductometric method such as the micellar mole fraction employing the Rubingh and Rodenas models, interaction parameter (β), activity coefficients of the mixed micelles, and excess Gibbs free energy using the Rubingh and Rodenas models and so on were evaluated. The activity coefficients values were lessened in electrolyte solvent in the entire systems showing the enhanced non-ideality of mixed system in electrolyte solution. At various temperatures, thermodynamic parameters were also evaluated in aqueous along with electrolyte solutions. The interactions amongst the studied constituents in the aqueous system were also evaluated by fluorescence and FT-IR studies and explored in detail.

Effect of Pharmaceutical Excipients on Cloud Point of Amphiphilic Drug Venlafaxine Hydrochloride Solutions

One of the characteristics of amphiphilic drug which may be a disadvantage is the phase separation or clouding phenomenon on heating which depends upon the nature, structure and concentration of the amphiphile, pressure, presence of additives, etc. The effect of various types of pharmaceutical excipients such as hydrotropes and β-cyclodextrin on the cloud point (CP) behaviour of amphiphilic drug venlafaxine hydrochloride (VFN) in sodium phosphate buffer sodium phosphate buffer (pH 6.7) solutions have been investigated in the present study. The anionic hydrotropes (sodium benzoate and sodium salicylate) increase the CP of VFN, when added in low concentrations, whereas at high concentration, decrease it. Cationic and non-ionic hydrotropes increase the CP of VFN solution at all the concentration. β-cyclodextrin behave like simple sugar is found to decrease the CP of the drug solutions at all concentrations. The thermodynamic parameters are also evaluated: where ΔG° is found to be negative and ΔH° and TΔS° values are negative as well as positive depending upon type and nature of hydrotropes. Based upon the result, storing formulations at temperatures significantly higher than the cloud point may result in phase separation and instability.

Effect of hydrotropes on the micellization behavior of sodium dodecyl sulfate/sodium dodecyl benzene sulfonate at various temperatures

ABSTRACTWith the aim of studying the effect of anionic hydrotrope sodium salicylate and nonionic hydrotrope resorcinol on the micellization behaviors of sodium dodecylsulfate (SDS) as well as sodium dodecylbenzenesulfonate (SDBS), experiments were carried out in aqueous medium at different temperatures using conductivity measurements. Hydrotrope addition leads to decrease in values of critical micelle concentration (cmc). The values of cmc of mixtures were obtained to be lower than the cmc value of ideal and pure component cmc values, which indicate negative deviation with synergistic interaction as confirmed by the negative interaction parameters (βm) values in mixed systems. In addition, the evaluated values of excess free energy of mixing () as well as free energy of micellization (ΔmicG○) are achieved to be negative showing stability of mixed systems.

Conductometric study of the mixing behaviour of sodium benzoate and salicylate with an anionic surfactant sodium lauroylsarcosinate

ABSTRACTEffects of two anionic hydrotropes – sodium benzoate (NaBz) and sodium salicylate (NaSal) – on the mixed-micelle formation with an amino-acid-based surfactant – sodium lauroylsarcosinate (SLS) – in water were investigated by the conductometric method. Specific conductivity was measured for SLS/NaBz/water and SLS/NaSal/water systems to determine the critical micelle concentration (cmc). Using the regular solution theory for non-ideal mixing, the pairwise interaction parameter, β12, and micellar composition, χ, were estimated in the mixed micelle. The cmc values of the surfactant–hydrotropes mixtures were generally lower than those predicted from the ideal mixing theory. The β12 values are generally negative for the two systems at all mole fractions with an average value of −2.83 for the SLS/NaBz and −3.31 for SLS/NaSal systems, respectively, indicative of a strong attractive interaction between the SLS/NaBz and SLS/NaSal mixed micelle. The calculated thermodynamic parameters of micellisation all indicated spontaneity in mixed-micelle formation for the systems studied.

Clouding phenomenon of amphiphilic drug promazine hydrochloride solutions: Influence of pharmaceutical excipients

Various additives viz. hydrotropes, bile salts, fatty acid and cyclodextrin effect on the cloud point (CP) behavior of amphiphilic drug promazine hydrochloride (PMZ) in 1mmoldm−3 14-4-14+10mmoldm−3 sodium phosphate (SP) buffer solutions have been investigated in the present study. These various additives are usually used as pharmaceutical excipients. The additives like anionic hydrotropes, bile salts and fatty acid salts increase the CP of PMZ, when added in low concentrations, whereas at high concentration, decrease it. Cationic and nonionic hydrotropes increase the CP of PMZ solutions at all concentration. Cyclodextrin behave like simple sugar is found to decrease the CP of the drug solutions at all concentrations. Gemini surfactant (14-4-14) has been found a better surfactant that can prevent clouding under physiological condition. It can thus be used as a drug-carrier system that increases the storage stability. The thermodynamic parameters are also evaluated: where ΔGco is found to be negative and ΔHco and TΔSco values are negative as well as positive depending upon type and nature of additive.

Aggregational behavior of alkanediyl-α,ω-bis(tetradecyldimethylammonium) dibromide series with ionic and nonionic hydrotropes at different temperatures

The purpose of the present study was to determine the influence of various additives on the aggregation behavior of gemini surfactants and to search for means which reduce the values of critical micelle concentration. The mixed micellar properties of cationic hydrotropes (aniline hydrochloride, para-toluidine hydrochloride, ortho-toluidine hydrochloride), anionic hydrotropes (sodium salicylate, sodium benzoate, sodium tosylate) and nonionic hydrotropes (phenol, resorcinol, pyrogallol) with conventional alkyl tetradecylammonium bromide (TTAB) and their dimeric homologues viz., 14-s-14, (s=4, 5, 6) in aqueous medium have been studied using conductometric technique at four different temperatures ranging from 298.15K to 313.15K. The evaluated thermodynamic parameters have been discussed in detail.

Investigation of micellar and phase separation phenomenon of phenothiazine drug promazine hydrochloride with anionic hydrotropes

The purpose of the present study was to determine the influence of various anionic hydrotropes on the self-aggregation and phase behavior of amphiphilic drug promazine hydrochloride (PMZ) and to search for means which reduce/increase the values of critical micelle concentration (cmc) and boost/suppress the cloud point (CP), respectively, used in pharmaceutical formulations. By using regular solution theory (RST) and Rosen's model various micellar and surface properties such as micellar composition, surface excess concentration (Γmax), interaction parameters (βm, βσ) etc. have been determined. The solution micellar behaviors were also investigated using Motomura and Rodenas models for defense and comparison of results. Thermodynamic parameters were also evaluated and discussed.

Clouding Behavior of Amphiphilic Drug Clomipramine Hydrochloride with Pharmaceutical Excipients

Abstract The clouding behavior of amphiphilic drug clomipramine hydrochloride (CLP) in presence of different additives like bile salts, hydrotropes (anionic, cationic and nonionic), fatty acids, sugars and cyclodextrin has been investigated. These additives are commonly used as drug delivery systems. The additives like anionic hydrotropes, bile salts and fatty acid salts increase the cloud point (CP) of CLP, when added in low concentrations, whereas at high concentration, decrease it. Cationic and nonionic hydrotropes increase the CP of CLP at all concentrations. All sugars decreased the CP because of their water structure making property. β-cyclodextrin behaves like simple sugar and decreases the CP of the drug solutions. The thermodynamic parameters are also evaluated: where ΔGc° is found to be negative and ΔHc° and TΔSc° values are negative as well as positive depending upon type and nature of additive.

Rod-like micelle templated synthesis of porous hydroxyapatite

Use of macromolecular templates for controlling nanostructures of inorganic materials is an active area of research. In particular, oriented growth of hydroxyapatite in organic matrix is of great relevance to understand biomineralisation of bone and its potential biomedical applications. Natural bone being a composite of hydroxyapatite and collagen fibers, crystallization of hydroxyapatite in fibrous assemblies could mimic such biomineralisation. This motivated us to investigate the role of long rod-like micelles in modulating the structure of hydroxyapatite particles. In this article, we report the preparation of porous hydroxyapatite nanorods using rod-like micelles made up of a cationic surfactant cetyltrimethylammonium bromide (CTAB) and anionic hydrotrope sodium salicylate (SS) as a templating agent. The successful formation of hydroxyapatite crystals is evident from XRD, FTIR, TGA, SEM and TEM analyses. It has been observed that large hydroxyapatite nanorods of diameter ∼50 nm are formed in surfactant mediated synthesis, whereas irregular shaped nanoaggregates of hydroxyapatite are obtained in the absence of surfactant. A comparative study on the porosity of hydroxyapatite clearly shows that monomodal distribution of mesopores with a peak at ∼30 nm in the absence of surfactant while bimodal distribution of mesopores having maxima at ∼4 nm and ∼45 nm appear in hydroxyapatite prepared in the presence of surfactant template.

Amphiphilic antidepressant drug amitriptyline hydrochloride under the influence of ionic and nonionic hydrotropes; micellization and phase separation

Herein we report the micellization and cloud point of an amitriptyline hydrochloride (AMT) under the influence of cationic, anionic and nonionic hydrotropes. Anionic hydrotropes were employed to know the micellar and surface behaviors, besides studying the clouding behavior of AMT drug with cationic, anionic and nonionic hydrotropes. Tensiometric study has been performed and the properties studied include the critical micelle concentration (cmc), maximum surface excess at the air/water interface (Γmax), the minimum area per of amphiphilic molecule at air/water interface (Amin), and the different thermodynamic parameters, besides clouding phenomenon. Interaction parameters of micelles (βm) and monolayer (βσ) indicate that drug-hydrotrope systems show better interaction at the interface than in micelles.

Rheological characterization of mixtures of cetyl trimethylammonium bromide and sodium butyl benzene sulfonate in aqueous solutions

The rheological behavior of mixed aqueous solutions of cetyl trimethylammonium bromide (CTAB) and anionic hydrotropes, such as sodium salts of n-butyl benzene sulfonate (Na-NBBS), iso-butyl benzene sulfonate (Na-IBBS) and tert-butyl benzene sulfonate (Na-TBBS), has been studied over a range of the hydrotrope concentration at different temperatures. The zero shear viscosity measurements for the mixed systems show a bimodal curve with a first viscosity maximum at a Na-BBS/CTAB ratio of approximately 0.3 and other ones at about 2.5. The three isomers of butyl benzene sulfonate (BBS) differ in their effects on the viscosity of the solutions. The difference in the viscosities of the mixed CTAB–hydrotrope solutions is more prominent at higher values of Na-BBS/CTAB ratio. Since the viscosity depends on the microstructure generated by the CTAB-BBS mixtures in solutions, the size and shape of the mixed micelles varies with the structure of the butyl group. The linear NBBS induces higher changes even at lower concentrations. The CTAB-hydrotrope solutions in the region of the first viscosity maxima exhibit Maxwellian fluid behavior where the mixed system is highly viscoelastic and the micelles are entangled. In the region of second viscosity maxima, however, the mixed solutions are non-viscoelastic with much lower values of storage and loss modulii. The living polymer formation by linear growth of CTAB micelles, on addition of hydrotropes, to very large aggregation number is evidenced from intrinsic viscosity and rheological properties of solutions.

Effects of pharmaceutical excipients on cloud points of amphiphilic drugs

The clouding behavior, i.e., formation of phase separation at elevated temperature (the temperature being known as cloud point (CP)), of three amphiphilic drugs, amitriptyline (AMT), clomipramine (CLP) and imipramine (IMP) hydrochlorides in the presence of various additives, like cationic surfactants (conventional and gemini), nonionic surfactants, bile salts, anionic hydrotropes, sodium salts of fatty acids and cyclodextrin has been investigated. These additives are generally used as drug delivery systems. The drugs used are tricyclic antidepressants. All the surfactants increase the CP of mixed micelles formed by cationic (conventional and gemini) and nonionic surfactants. Hydrotropes, bile salts and fatty acid salts, when added in low concentrations, increase the CP, whereas at high concentrations, they decrease it. β-Cyclodextrin behaves as simple sugar and decreases the CP of the drug solutions.

Dilution induced thickening in hydrotrope-rich rod-like micelles

Dilution induced changes in the microstructure and rheological behavior of micelles formed by a cationic surfactant–anionic hydrotrope mixture has been investigated in the hydrotrope-rich region. The surfactant used is cetyltrimethylammonium bromide (CTAB) and the hydrotropic salt is sodium 3-hydroxy naphthalene 2-carboxylate (SHNC). The concentration of the mixture is varied from 0.5% to 10.0% w/w (ϕ=0.005–0.100) at a fixed weight ratio of hydrotrope to surfactant (85:15). Rheological studies indicate Newtonian flow behavior at low and high volume fractions (0.005 and 0.100) while a shear thinning behavior is observed at intermediate volume fractions. The zero-shear viscosity η0 also passes through a maximum upon changes in the concentration. The most striking feature in our study is that a low viscosity Newtonian fluid transforms to a viscoelastic fluid, upon dilution, and then again to a Newtonain fluid. Small angle neutron scattering studies of 10.0% micellar solution show the presence of rod-like aggregates. Upon dilution, the scattering intensity per unit concentration shows an increase in the low q-region. The nature of pair distance distribution function and subsequent model fitting indicates a transition from rod-like micelles to unilamellar vesicles upon dilution. This behavior is explained in terms of the volume fraction dependant solubilization of hydrotropes in the rod-like micelles and consequent changes in the composition of the mixed micelles.

Mixing Behavior of Anionic Hydrotropes with Cationic Gemini Surfactants

In this article, we report the results of the mixing behavior of alkanediyl-α,ω-bis(dimethylcetylammonium bromide) gemini surfactants with anionic hydrotropes (sodium salicyalte, sodium benzoate, and sodium tosylate) in aqueous solutions using conductivity measurements. The critical micelle concentration (cmc) for different mixing mole fractions at different temperatures, their ideal cmc values, and different interaction parameters have been estimated. The results show that the mixing behavior is nonideal and the interactions among the surfactants and the hydrotropes are synergistic in nature.

Influence of SDS and two anionic hydrotropes on the micellized state of the triblock copolymer E 71G 7E 71

Complex formation between the triblock copolymer E 71G 7E 71, where E denotes ethylene oxide, the central hydrophobic block, phenyl glycidyl ether, is denoted as G, and the subscripts denote the block length, the surfactant sodium dodecyl sulfate (SDS), and the penicillins cloxacillin and dicloxacillin, which can be considered as hydrotropes has been investigated by dynamic light scattering (DLS) and isothermal titration calorimetry (ITC). The different copolymer/amphiphile systems have been studied at a constant copolymer concentration of 10 g dm −3 and at different amphiphile concentrations. For all systems, the relaxation time distributions show a well-defined single mode with a shift toward slightly faster times, which indicates that the electrostatic interactions between the complexes is minimum, and so it is possible to estimate a size in terms of the apparent hydrodynamic radii. For ITC the amphiphile solutions were titrated in two different forms: as monomers (below the cmc) and as aggregates. The data indicate that the interaction between the surfactant and the hydrotropes with the copolymer occurs even at the lowest SDS concentration measured.