Role of surfactants in clouding phenomenon of imipramine hydrochloride

The clouding behavior of tricyclic antidepressant drug imipramine hydrochloride (IMP) in aqueous solution has been studied in presence of surfactants. A pH increase in the presence as well as in the absence of surfactants decreased the CP. Drug molecules become neutral at high pH and therefore head–head repulsion decreases which lead to CP decrease. Addition of non-ionic and cationic surfactants increased the CP whereas anionic surfactants showed a peaked profile. Effect of CTAB/TX-100 at different fixed drug concentrations showed that at all surfactant concentrations the CP value was higher for higher drug concentrations. However, variation of pH produced opposite effect: CP at all CTAB/TX-100 concentrations decreased with increasing pH. All results are interpreted in terms of increase in hydrophobicity or hydrophilicity of micelles on addition of surfactants.     

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.     

Aggregation behavior of fluorocarbon and hydrocarbon cationic surfactant mixtures: a study of 1H NMR and 19F NMR

The aggregation behavior and the interaction of four mixed systems for a cationic fluorocarbon surfactant, diethanolheptadecafluoro-2-undecanolmethylammonium chloride (DEFUMACl), mixing with cationic hydrocarbon surfactants, alkyltrimethylammonium chloride, CnTACl (n=12, 14, 16, and 18; where n=12 is DTACl, n=14 is TTACl, n=16 is CTACl, and n=18 is OTACl), were studied by 1H and 19F NMR in more detail. The results of 19F NMR measurements strongly indicate that in the three mixed systems of DEFUMACl/DTACl, DEFUMACl/TTACl, and DEFUMACl/CTACl at different molar fractions of fluorocarbon surfactant (alphaF=(cDEFUMACl/cDEFUMACl+cCnTACl)), with an increase of the total concentration of fluorocarbon and hydrocarbon surfactants (cT=cF+cH), the mixed micelles at the first break point and the individual DEFUMACl micelles at the second break point form. However, three different types of micelles were determined in DEFUMACl/OTACl mixtures by 19F NMR measurements, OTACl-rich and DEFUMACl-rich mixed micelles and individual DEFUMACl micelles, respectively. The chemical shifts of proton Deltadelta (1H) for -CH3 in the mixed systems of DEFUMACl/CnTACl (n=12, 14, 16, and 18) have different variation trends from the 19F NMR measurements. For the two systems of DEFUACl/DTACl and DEFUMACl/TTACl, the mixed micelles form at the first break point. At the second break point, for lower alpha F values the DTACl-rich and TTACl-rich mixed micelles form with a strong downfield shift and for higher alpha F values DEFUMACl-rich mixed micelles form with a strong upfield. For the other two systems of DEFUMACl/CTACl and DEFUMAC/OTACl, the chemical shifts of proton Deltadelta (1H) of -CH3 increase with an increase of the total concentration of DEFUMACl/CTACl or OTACl, and mixed CH- and CF-surfactant micelles form. At higher total concentration, the greater effect of fluorinated chains of DEFUMACl on CH-chains was obvious, resulting in the strong upfield chemical shifts. In cationic fluorocarbon and hydrocarbon surfactant mixtures, the different kinds of micelles observed by 19F and 1H NMR measurements could be caused by the increase in alkyl chain length of hydrocarbon surfactants with different critical micelle concentrations. Combining two theoretical models for mixing, for the four different chain-length hydrocarbon surfactants studied, one can conclude that the two components of mixtures interact with each other and form mixed micelles in two completely different ways according to their molecular properties and cmc values in a certain range of total concentrations. One is close to an ideal mixing case with the formation of one type of mixed micelles, such as the DEFUMACl/DTACl and DEFUMACl/TTACl systems. The other is a demixing case with the formation of two types of micelles, i.e., fluorocarbon-rich and hydrocarbon-rich mixed micelles, such as DEFUMACl/CTACl and DEFUMACl/OTACl systems. However, as the total concentrations of the mixed systems are high enough, the four systems tend to demix and to form individual micelles of corresponding components due to the initial respective interaction between fluorocarbon and hydrocarbon chains. That is to say, at high total concentration, the individual DEFUMACl micelles in all four systems could form. These results may be primarily directed toward acquiring an understanding of the mechanism of CF-CH mixtures in aqueous solution and secondarily directed toward providing more detailed information on nonideal mixing.     

Influence of additives on the clouding behavior of amphiphilic drug solutions

The present work focuses on the clouding phenomenon in an amphiphilic drug [amitriptyline (AMT), which is a tricyclic antidepressant] solution. A 50-mM AMT solution prepared in 10 mM of sodium phosphate (SP) buffer was taken where the cloud point (CP) was found to decrease with increasing pH. The same CP decreasing trend (with pH increase) followed in the presence of a fixed concentration (50 mM) of added salts [NaBr, and tetra-n-butylammonium bromide (TBuAB)]. The addition of increasing amounts of quaternary bromides (tetramethylammonium bromide, tetraethylammonium bromide, tetra-n-propylammonium bromide, TBuAB, and tetra-n-pentylammonium bromide) to 50 mM of AMT solution (prepared in 10 mM of SP buffer) caused continuous increase in CP, which was found to be dependent upon the alkyl chain length of that particular salt. The similar type of CP increase was also observed in the presence of conventional (cetyltrimethylammonium bromide and tetradecyltrimethylammonium bromide) and gemini surfactants [bis(hexadecyldimethylammonium)hexane, bis(hexadecyldimethylammonium)pentane, and bis(hexadecyldimethylammonium)butane]. The overall behavior was discussed in terms of electrostatic interactions, micellar growth, and mixed micelle formation.     

水溶液中两亲药物盐酸异丙嗪-表面活性剂体系的胶束化行为

The behavior of the mixed amphiphilic drug promethazine hydrochloride(PMT) and cationic as well as nonionic surfactants was studied by tensiometry.The cmc values of the PMT-surfactant systems decrease at a surfactant mole fraction of 0.1 and it then becomes constant.The critical micelle concentration(cmc) values are lower than the ideal cmc(cmc*) values for PMT/TX-100,PMT/TX-114,PMT/Tween 20,and PMT/Tween 60 systems.For the PMT/Tween 40,PMT/Tween 80,PMT/CPC,and PMT/CPB systems the cmc values are close to the cmc* values.This indicates that PMT forms mixed micelles with these surfactants by attractive interactions.The surface excess(Γmax) decreases in the presence of surfactants.The rigid structure of the drug makes adsorption easier and the contribution of the surfactant at the interface decreases.The interaction parameters βm(for the mixed micelles) and βσ(for the mixed monolayer) are negative indicating attraction among the mixed components.     

Influence of electrolytes/non-electrolytes on the cloud point phenomenon of the aqueous promethazine hydrochloride drug solution

We have studied the clouding phenomena in promethazine hydrochloride (PMT) aqueous solutions in presence of electrolytes and non-electrolytes. PMT, a tranquillizer, shows phase separation. The cloud point (CP) decreases with increase in pH due to deprotonation of drug molecules. At constant pH, increasing salt addition causes an increase in CP, which is explained on the basis of their position in Hofmeister series and their hydrated radii. With quaternary salts CP increases due to adsorption/mixed micelle formation. Ureas decrease the CP and the behavior is explained on the basis of removal of water from the headgroup region.     

Electrophoretic separations in poly(dimethylsiloxane) microchips using mixtures of ionic,nonionic and zwitterionic surfactants

The use of surfactant mixtures to affect both EOF and separation selectivity in electrophoresis with PDMS substrates is reported, and capacitively coupled contactless conductivity detection is introduced for EOF measurement on PDMS microchips. First, the EOF was measured for two nonionic surfactants (Tween 20 and Triton X‐100), mixed ionic/nonionic surfactant systems (SDS/Tween 20 and SDS/Triton X‐100), and finally for the first time, mixed zwitterionic/nonionic surfactant systems (TDAPS/Tween 20 and TDAPS/Triton X‐100). EOF for the nonionic surfactants decreased with increasing surfactant concentration. The addition of SDS or TDAPS to a nonionic surfactant increased EOF. After establishing the EOF behavior, the separation of model catecholamines was explored to show the impact on separations. Similar analyte resolution with greater peak heights was achieved with mixed surfactant systems containing Tween 20 and TDAPS relative to the single surfactant system. Finally, the detection of catecholamine release from PC12 cells by stimulation with 80 mM K⁺ was performed to demonstrate the usefulness of mixed surfactant systems to provide resolution of biological compounds in complex samples.     

Micellization and Clouding Phenomenon of Phenothiazine Drug Promethazine Hydrochloride: Effect of NaCl and Urea Addition

Herein we report the micellization and clouding behavior of promethazine hydrochloride (PMT) in absence and presence of NaCl/ureas. The critical micelle concentration (CMC) of PMT is measured by conductivity method and the values decrease with increasing the NaCl concentration. With increasing the temperature, the CMC first increases then decreases. At 25°C, the maximum CMC values were obtained (with or without NaCl). The thermodynamic parameters are evaluated which indicate more stability of the PMT solution in presence of NaCl. PMT shows phase separation also. The cloud point (CP) of PMT decreases with increase in pH due to deprotonation of the drug molecules. Ureas decreased the CP and the behavior is explained on the basis of removal of water from the head group region.     

高浓度区正负离子表面活性剂混合胶团的形状与大小变化

本文研究高浓度区正、负离子表面活性混合胶团的形态及大小随浓度的变化规律。根据正、负离子表面活性剂混合体系的相行为,胶团溶液的光散射以及流变性质测量,提出了混合胶团的棒-球转变模型。认为在较高浓度,随浓度增大,混合胶团经历了一个长棒变短,短棒变为球状的转变过程。     

链式与面式两种不对称疏水结构表面活性剂之间的相互作用热力学

本文通过等温滴定量热法(ITC)、电导法和浊度法研究了阴离子生物表面活性剂脱氧胆酸钠(NaDC)及其与相反电荷的十二烷基三甲基溴化铵(DTAB)在水溶液中的自组装热力学.ITC结果支持了NaDC在水溶液中先生成预胶束再形成稳定胶束的分步聚集模型,由此得到了NaDC的预胶束和胶束化过程的一系列热力学参数,并讨论了它们形成的热力学机理.进一步研究了具有头-尾链式和疏水-亲水刚性面式非对称结构的DTAB/NaDC混合体系的聚集热力学行为,得到了富NaDC临界混合胶束浓度(cmcmix)、富DTAB临界胶束浓度(CM)及对应过程的转变焓.结果表明,NaDC面式结构与DTAB链式结构的对称性差异以及相反电荷的相互作用,导致混合体系有别于单一表面活性剂或头-尾链式结构的混合体系的聚集行为.混合溶液的聚集行为受控于表面活性剂浓度和摩尔分数的变化.富NaDC胶束化过程为熵驱动,而富DTAB的两种胶束形态转变过程为熵焓共同驱动的热力学机理.这些结果对于从热力学角度认识胆汁酸盐的自组装机理以及与传统的头-尾链式结构的表面活性剂相互作用机理和相行为有重要的意义.     

Physicochemical studies of pyridinium gemini surfactants with promethazine hydrochloride in aqueous solution

The mixed micellization and interfacial behavior of pyridinium gemini surfactants, 1,1'-(1,1'-(ethane-1,2-diylbis-(sulfanediyl))bis(alkane-2,1-diyl))dipyridinium bromide, i.e., [12-(S-2-S)-12], [14-(S-2-S)-14], [16-(S-2-S)-16] with a phenothiazine tranquilizer drug, promethazine hydrochloride (PMT), has been investigated by conductivity, surface tension and steady state fluorescence measurements. Different spectroscopic techniques like fluorescence, UV-visible and NMR were also employed to understand the nature of interactions between the pyridinium gemini surfactants and PMT. The various micellar, interfacial and associated thermodynamic parameters for different mole fractions of PMT-pyridinium gemini surfactant mixtures have been evaluated. Synergism was observed in the mixed micelle as well as the monolayer formed by these mixtures. The fluorescence quenching experiment indicates that the interactions between PMT and surfactants are hydrophobic in nature. The UV-visible measurements reveal the distinct formation of a drug-surfactant complex. The detailed mechanism for the type of interactions was further studied by NMR titrations which show cation-π interactions between PMT and pyridinium gemini surfactant molecules.     

Lidocaine and soyasterole-PEG-16-ether — investigations on the interaction between an amphiphilic drug and a nonionic surfactant in aqueous solution

In order to study the interactions between the surface active local anaesthetic drug lidocaine and the nonionic surfactant soyasterole-PEG-16-ether firstly the self association of the drug in aqueous solution was investigated by different methods. Transmission electron microscopy hinted at micellization and surface tension measurements resulted in a CMC of 12.9% (salt form) and 0.08% (base form), respectively, whereas solubilization experiments, NMR spectroscopy and osmotic pressure measurements obviously disproved the existence of drug micelles. The detected CMC only meant a surface saturation and the TEM pictures probably showed artifacts. In diluted systems containing both drug and surfactant no formation of mixed micelles took place, as pointed out by the tensiometric determination of the CMC of the mixtures showing no minimum in the CMC/% drug-curve. Also, gel permeation chromatography clearly separated surfactant micelles and drug molecules. In contrast to this, evident interactions between the base form of the drug and the surfactant occurred when the drug concentration was increased: the dynamic viscosity of the systems rose distinctly, probably caused by growth of the surfactant associates to a more rodlike form. The salt form had nearly no influence on the viscosity of the preparations.     

Application of a chemical equilibrium model to thermodynamic functions of transfer of alcohols from water to aqueous surfactants

In ternary aqueous solutions, hydrophobic solutes such as alcohols tend to aggregate with surfactants to form mixed micelles. These systems can be studied by meas of the functions of transfer of hydrophobic solutes from water to aqueous solutions of surfactant. These thermodynamic functions often go through extrema in the critical micellar concentration (CMC) region of the surfactant. A simple model based on interactions between surfactant and hydrophobic solute monomers, on the distribution of the hydrophobic solute between water and the micelles and on the shift in the CMC induced by the hydrophobic solute, can simulate the magnitude and trends of the transfer functions using parameters which are mostly derived from the binary systems. In order to check the model more quantitatively, volumes and heat capacities of transfer of alcohols from water to aqueous solutions of a nonionic surfactant, octyldimethylamine oxide, were measured. A quantitative agreement was achieved with three adjustable parameters. Good fits are also obtained for the transfers to the ionic surfactants, octylamine hydrobromide and sodium dodecylsulfate. When the equilibrium displacement contribution is small, the distribution constants and the partial molar properties of the alcohols in the micellar phase agree well with the parameters obtained with similar models.     

Viscosity-Temperature Behavior of Hydroxypropyl Cellulose Solution in Presence of an Electrolyte or a Surfactant: A Convenient Method to Determine the Cloud Point of Polymer Solutions

The viscosity of hydroxypropyl cellulose (HPC) solution with or without an additive has been measured continuously as a function of temperature with the help of a vibro-viscometer. The viscosity of the polymer solution showed a gradual decrease initially with increase in temperature until a particular point beyond which there was a sharp decrease in the viscosity, which coincided with the clouding of the solution. The cloud point temperature (CP) of the polymer solution was determined from the first derivative plot of viscosity vs. temperature. Effect of addition of an electrolyte or a surfactant on the CP of HPC solution has also been studied. While a decrease in CP of HPC solution in presence of fluoride, chloride, or bromide ions was observed, presence of iodide or thiocyanide ions led to an increase in the CP. However, presence of an ionic surfactant initially lowered the CP but beyond a particular surfactant concentration a sharp increase in cloud point was observed due to interaction of the surfactant with the polymer. The results suggest that surfactants with longer hydrophobic tail or more hydrophobic groups have more affinity for HPC.     

Using Calixarenes To Model Polyelectrolyte Surfactant Nucleation Sites

The formation of mixed micelles composed of dodecyltrimethylammonium bromide (C₁₂TAB) and a hexamethylated p‐sulfonatocalix[6]arene (SC6HM) was studied by several techniques. It was found that above the critical aggregation concentration the concentrations of free and micellized surfactant are strongly related to that of SC6HM. When there is free SC6HM in solution, the addition of C₁₂TAB mainly results in an increase in the concentration of micellized surfactant, but when all SC6HM has been aggregated, the addition of C₁₂TAB results in a substantial increase in the concentration of free surfactant in solution. When the concentration of free surfactant is equal to the critical micelle concentration of the pure system, a second independent aggregation process is observed. This aggregation behavior has many features that are similar to those of more complex systems that involve surfactants in the presence of oppositely charged polyelectrolytes. In this way, calixarenes can serve as simple models to mimic polyelectrolytes and to gain insight into the complex behavior displayed by these macromolecules.     

Solubilization mechanism of vesicles by surfactants: effect of hydrophobicity

Simulations based on dissipative particle dynamics are performed to investigate the solubilization mechanism of vesicles by surfactants. Surfactants tend to partition themselves between vesicle and the bulk solution. It is found that only surfactants with suitable hydrophobicity are able to solubilize vesicles by forming small mixed micelles. Surfactants with inadequate hydrophobicity tend to stay in the bulk solution and only a few of them enter into the vesicle. Consequently, the vesicle structure remains intact for all surfactant concentrations studied. On the contrary, surfactants with excessive hydrophobicity are inclined to incorporate with the vesicle and thus the vesicle size continues to grow as the surfactant concentration increases. Instead of forming discrete mixed micelles, lipid and surfactant are associated into large aggregates taking the shapes of cylinders, donuts, bilayers, etc. For addition of surfactant with moderate hydrophobicity, perforated vesicles are observed before the formation of mixed micelles and thus the solubilization mechanism is more intricate than the well-known three-stage hypothesis. As the apparent critical micellar concentration (φ(s,v)(a,CMC)) is attained, pure surfactant micelles form and the vesicle deforms because the distribution of surfactant within the bilayer is no longer uniform. When the surfactant concentration reaches φ(s,v)(p), the vesicle perforates. The extent of perforation grows with increasing surfactant concentration. The solubilization process begins at φ(s,v) (sol), and lipids leave the vesicle and join surfactant micelles to form mixed micelles. Eventually, total collapse of the vesicle is observed. In general, one has φ(s,v)(a,CMC)≤φ(s,v)(p)≤φ(s,v)(sol).     

Variegated micelle surfaces: correlating the microstructure of mixed surfactant micelles with bulk solution properties

Electron paramagnetic resonance, viscosity, and small-angle neutron scattering (SANS) measurements have been used to study the interaction of mixed anionic/nonionic surfactant micelles with the polyampholytic protein gelatin. Sodium dodecyl sulfate (SDS) and the nonionic surfactant dodecylmalono-bis-N-methylglucamide (C12BNMG) were chosen as "interacting" and "noninteracting" surfactants, respectively; SDS micelles bind strongly to gelatin but C12BNMG micelles do not. Further, the two surfactants interact synergistically in the absence of the gelatin. The effects of total surfactant concentration and surfactant mole fraction have been investigated. Previous work (Griffiths et al. Langmuir 2000, 16 (26), 9983-9990) has shown that above a critical solution mole fraction, mixed micelles bind to gelatin. This critical mole fraction corresponds to a micelle surface that has no displaceable water (Griffiths et al. J. Phys. Chem. B 2001, 105 (31), 7465). On binding of the mixed micelle, the bulk solution viscosity increases, with the viscosity-surfactant concentration behavior being strongly dependent on the solution surfactant mole fraction. The viscosity at a stoichiometry of approximately one micelle per gelatin molecule observed in SDS-rich mixtures scales with the surface area of the micelle occupied by the interacting surfactant, SDS. Below the critical solution mole fraction, there is no significant increase in viscosity with increasing surfactant concentration. Further, the SANS behavior of the gelatin/mixed surfactant systems below the critical micelle mole fraction can be described as a simple summation of those arising from the separate gelatin and binary mixed surfactant micelles. By contrast, for systems above the critical micelle mole fraction, the SANS data cannot be described by such a simple approach. No signature from any unperturbed gelatin could be detected in the gelatin/mixed surfactant system. The gelatin scattering is very similar in form to the surfactant scattering, confirming the widely accepted picture that the polymer "wraps" around the micelle surface. The gelatin scattering in the presence of deuterated surfactants is insensitive to the micelle composition provided the composition is above the critical value, suggesting that the viscosity enhancement observed arises from the number and strength of the micelle-polymer contact points rather than the gelatin conformation per se.     

SANS study of tuning of clouding in charged micellar system

We report the phenomenon of clouding in charged micellar solution of sodium dodecyl sulfate (SDS) surfactant with varying concentration of tetrabutylammonium bromide (TBAB) salt. The cloud point (CP) temperature is found to decrease significantly with TBAB concentration. Small-angle neutron scattering (SANS) studies have been performed on these systems to understand the evolution of structure and interaction of micelles prior and after the CP. Data are analyzed using Baxter’s sticky hard-sphere potential between the micelles as approaching the CP. It is found that the attractive potential amongst micelles increases with temperature leading to clustering at CP. Both the micelles and clusters coexist at CP and even at temperatures much higher than CP. The propensity of cluster formation strongly depends on the TBAB concentration where higher TBAB concentration provides smaller temperature range over which the clusters are formed. SANS data from clusters show a Porod scattering in the low-Q region, suggesting a very large size of the clusters. The stability of these clusters against phase separation is examined by the time-dependent SANS and compared for different TBAB concentrations.     

Cloud Point Phenomenon in Amphiphilic Drug Promethazine Hydrochloride+Electrolyte Systems

Herein we report clouding phenomenon occurring in amphiphilic drug promethazine hydrochloride (PMT) in the presence of electrolytes. The CP of 50 mM drug solution, prepared in 10 mM sodium phosphate buffer, was found to decrease with increasing pH due to deprotonation of drug molecules at high pH. Addition of inorganic salts (KF, KCl and KBr) to drug solutions at fixed pH (6.7) and drug concentration (50 mM) caused an increase in CP. The results have been discussed on the desorption/adsorption of counterions to the headgroups. Cations also increased the CP by affecting the water structure with their effectiveness being in the order: Li⁺<Na⁺<K⁺<NH₄ ⁺. In the presence of NaCl, increase in drug concentration increased the CP while increase in pH showed an opposite trend.     

Supramolecular Systems Based on Novel Mono‐ and Dicationic Pyrimidinic Amphiphiles and Oligonucleotides: A Self‐Organization and Complexation Study

Novel mono‐ and dicationic pyrimidinic surfactants are synthesized and their aggregation behavior is studied by methods of tensiometry and nuclear magnetic resonance (NMR) self‐diffusion. To estimate their potentiality as gene delivery agents, the complexation with oligonucleotides (ONus) is explored by dynamic light scattering (DLS) and zeta‐potential titration methods and ethidium bromide exclusion experiments. Bola‐type pyrimidinic amphiphile (BPM) demonstrates rather a weak affinity to ONus. Although it induces mixed associations with ONus, only slight charge compensation changes occur at a large excess of bola, with no recharging reached. Similarly, the ethydium bromide exclusion study reveals a slow increase in the binding capacity toward an ONu with an increment in BPM concentration. The monocationic pyrimidinic surfactant (MPM) and its gemini analogue (GPM‐1) are ranked as intermediates in both their aggregative activity and complexing properties toward ONus. They both form mixed associates with ONus well below the critical micelle concentrations (cmcs) of 2 and 15 mM respectively. However, GPM‐1 has a much lower isoelectric point at the molar ratio surfactant/ONu r～1 compared to r～3 for MPM. This probably indicates a larger electrostatic contribution to the ONu complexation in the case of GPM‐1. The most hydrophobic pyrimidinic surfactant (GPM‐2), bearing three alkyl tails, demonstrates enhanced aggregative activity and binding capacity toward ONus as compared to former pyrimidinic surfactants. Due to effective aggregative (low cmc of 0.04 mM ) plus binding properties (fraction of bound ONu β=0.76 at r=2.5), GPM‐2 may be ranked as a promising agent for wider biological applications.