Adsorption and Micellization Behavior of Cationic Surfactants (Gemini and Conventional)—Amphiphilic Drug Systems

In the present work, the behavior of mixed drug–surfactant systems has been studied by surface tension measurements. The drug used in this work is adiphenine hydrochloride (ADP) and the surfactants are of m-s-m type geminis, i.e., alkanediyl-α,ω-bis(dimethylalkylammonium bromide), with m = (14, 16), s = (4, 5, 6), and conventional alkyltrimethylammonium bromides (CTAB, TTAB). The excess surface concentration (Γ _max ) increases and the minimum head group area at the air/water interface (A _min) decreases with increasing concentration of surfactant in the drug solution. Both the critical micelle concentration (cmc) and ideal cmc (cmc*) values decrease with mole fraction of surfactants. Also, the cmc values are lower than cmc*, indicating attractive interactions are present in the mixed micelles. The mole fractions of surfactant in the micelles $ \left( {X_{1}^{m} } \right) $ and monolayers $ \left( {X_{1}^{\sigma } } \right) $ , as well as the respective interaction parameters ( $ \beta^{m} $ , $ \beta^{\sigma } $ ), indicate that monolayer formation is easier than micelle formation due to the rigid hydrophobic part of the drug.     

The Effect of Added Salts and Organics on the Cloud Point of TX‐114

Herein we report the effect of additives (salts and organics) on the cloud point (CP) of nonionic surfactant Triton X‐114 (TX‐114) aqueous solutions. CP showed a concentration dependent variation in the absence of any added compound. Addition of quaternary ammonium (or phosphonium) bromides to 0.8 mM TX‐114 solutions increased the CP. It was found that long chain alcohols and amines decreased the CP of 0.8 mM TX‐114 +80 mM Bu₄AmB aqueous system, while it either remained constant or increased in the presence of short chain additives. The effect of first group additives (long chain) can be explained by considering that these additives solubilize in interfacial region and assist in micellar growth. Short chain additives remain in aqueous phase and affect the micelle hydration by affecting the solvent. Pentylamine behaved differently than pentanol: pentylamine increased the CP (like short chain additives) while pentanol decreased the CP. In pentylamine, the hydrophilicity of NH₂ group and its dissociation into NH₃ ⁺ dominates over the hydrophobicity of its alkyl chain. Aliphatic hydrocarbons first decreased and then increased the CP. The overall behavior depended upon the chain length of the hydrocarbon. With decane, the CP decreasing region disappeared completely.     

Nonelectrolyte-Induced CP Variation of TX-114＋TBAB System

The effects of nonelectrolytes(ureas,amino acids,sugars)on the cloud point(CP)of nonionic surfactantTriton X-114(TX-114)and tetra-n-butylammonium bromide(TBAB)system were studied.Ureas as well as thioureasincreased the CP.Behaviors of amino acids depended upon their nature.Nonpolar and uncharged polar anlino acidswere less effective in changing the CP.However,tryptophan and phenylalanine increased the CP sharply.Acidicamino acid(aspartic acid)and sugars decreased the CP.The results were explained in terms of their effect on waterstructure.Amino acids got solubilized either in the micellar interior or in the bulk phase.     

Aqueous amphiphilic drug (amitriptyline hydrochloride)-bile salt mixtures at different temperatures

The formation of mixed micelles built of 7,12-dioxolithocholic and the following hydrophobic bile acids was examined by conductometric method: cholic (C), deoxycholic (D), chenodeoxycholic (CD), 12-oxolithocholic (12-oxoL), 7-oxolithocholic (7-oxoL), ursodeoxycholic (UD) and hiodeoxycholic (HD). Interaction parameter (β) in the studied binary mixed micelles had negative value, suggesting synergism between micelle building units. Based on β value, the hydrophobic bile acids formed two groups: group I (C, D and CD) and group II (12-oxoL, 7-oxoL, UD and HD). Bile acids from group II had more negative β values than bile acids from group I. Also, bile acids from group II formed intermolecular hydrogen bonds in aggregates with both smaller (2) and higher (4) aggregation numbers, according to the analysis of their stereochemical (conformational) structures and possible structures of mixed micelles built of these bile acids and 7,12-dioxolithocholic acid. Haemolytic potential and partition coefficient of nitrazepam were higher in mixed micelles built of the more hydrophobic bile acids (C, D, CD) and 7,12-dioxolithocholic acid than in micelles built only of 7,12-dioxolithocholic acid. On the other hand, these mixed micelles still had lower values of haemolytic potential than micelles built of C, D or CD. The mixed micelles that included bile acids: 12-oxoL, 7-oxoL, UD or HD did not significantly differ from the micelles of 7,12-dioxolithocholic acid, observing the values of their haemolytic potential.     

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.     

Cloud point variation of amphiphilic drug promethazine hydrochloride with added surfactants

In this paper we report clouding phenomenon occurring in an amphiphilic phenothiazine drug promethazine hydrochloride (PMT) in presence of surfactants. Cationic and nonionic surfactants increase the CP of 75 mM PMT solutions (prepared in 10 mM sodium phosphate buffer). These surfactants form mixed micelles with PMT. Anionic surfactants also form mixed micelles with the drug but the CP behavior is different by showing a peaked behavior. At low concentrations, anionic surfactants hinder micelle formation by forming ion-pairs whereas the usual CP decreasing effect at higher concentrations is due to mixed micellization. The CP behavior of 75 mM PMT+50 mM TBAB+surfactant systems is also explored which is found similar to PMT+surfactant systems with the difference only in magnitude of the clouding temperature.     

Effect of electrolytes on the cloud point of chlorpromazine hydrochloride solutions

Cloud point (CP) phenomenon occurring in amphiphilic drug chlorpromazine hydrochloride (CPZ) solutions with and without salts is reported herein. The CP of a 50mM CPZ solution (prepared in 10mM sodium phosphate, SP, buffer) was found to decrease with increasing pH, both in the absence as well as presence (50mM) of added salts (NaCl, NaBr, LiBr, KBr, tetra-n-butylammonium bromide). Whereas, at a fixed concentration of NaCl, the CP increased with increasing CPZ concentration, addition of increasing amounts of salts (NaF, NaCl, NaBr, LiCl, KCl) to 50mM CPZ solution (at pH 6.7) caused continuous increase in CP. On the basis of these studies the binding-effect orders of counterions and co-ions have been deduced, respectively, as: Br(-)>Cl(-)>F(-) and Li(+)>Na(+)>K(+). The similar trend of increasing CP with addition of increasing amounts of quaternary bromides (tetramethylammonium bromide, TMeAB; tetraethylammonium bromide, TEtAB; tetra-n-propylammonium bromide, TPrAB; tetra-n-butylammonium bromide, TBuAB; tetra-n-pentylammonium bromide, TPeAB) to 50mM CPZ solutions (at pH 6.7) was found to be dependent upon the alkyl chain length of the particular salt. The overall behaviour has been discussed in terms of electrostatic interactions, micellar growth, and mixed micelle formation.