ABSTRACT
PURPOSE: To determine the cloud point of a variety of nonionic surfactants and to search for means to raise the surfactant cloud point in liquid formulations. METHODS: Cloud points of nonionic surfactants were determined visually in a water bath. Organic compounds, many of which have been used as pharmaceutical excipients, were tested initially for effect on the cloud point of poloxamine 908. Four effective cloud point boosters (CPBs) from different structural classes were further tested on additional surfactants. RESULTS: A number of compounds can raise the cloud point of nonionic surfactants. These cloud point boosters are classified into two categories: nonionic and ionic. The nonionic CPBs include poly(ethylene glycols), propylene glycol, methanol, ethanol, isopropanol, and 2-hydroxypropyl-beta-cyclodextrin. They are effective at molar concentrations. The ionic CPBs include anionic and cationic surfactants, charged phospholipids, long chain fatty acids, and bile salts. They are effective at millimolar concentrations. CONCLUSIONS: The cloud point of nonionic surfactants used in liquid formulations can be modulated through the proper choice of excipient.
Subject(s)
Excipients/chemistry , Surface-Active Agents/chemistry , Alcohols/chemistry , Buffers , Carbohydrates/chemistry , Chromatography, Gel , Chromatography, High Pressure Liquid , Drug Carriers/chemistry , Ethylenediamines/chemistry , Fatty Acids/chemistry , Ionophores/chemistry , Ions , Particle Size , Phospholipids/chemistry , Polyethylene Glycols/chemistry , Solubility , TemperatureABSTRACT
The electrokinetic chromatography (EKC) of a novel mixed surfactant system consisting of oppositely charged surfactants, sodium dodecyl sulfate (SDS) and n-dodecyltrimethylammonium bromide (DTAB), was investigated. The chromatographic characteristics of large liposome-like spontaneous vesicles and rodlike mixed micelles formed from the mixture were explored and compared with those of SDS micelles. Separations of a series of n-alkylphenones showed that the spontaneous vesicles provided about a 2 times wider elution window than SDS micelles. Both vesicle and mixed micelle systems were found to provide larger methylene selectivity than SDS. The different elution order of a group of nitrotoluene geometric isomers with DTAB/SDS spontaneous vesicles and SDS micelles pseudostationary phases suggested the possibility of different separation mechanisms with these two systems. Comparisons of polar group selectivity, retention, and efficiency were made between vesicles, mixed micelles, and SDS micelles. The correlation between the logarithms of the retention factors (log k') and octanol-water partition coefficients (log P(ow)) for a group of 20 neutral compounds was also studied with DTAB/SDS vesicles. Spontaneous vesicles have great potential as a pseudostationary phase in electrokinetic chromatography.
