Cloud point of nonionic surfactants: modulation with pharmaceutical excipients.
OBJECTIVE
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.
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Nycomed Amersham Imaging, Wayne, Pennsylvania 19087-8630, USA. george.na@us.nycomed-amersham.com
Yuan
B O
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Stevens
H J
HJ
Weekley
B S
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Rajagopalan
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D000438:Alcohols / Q000737:chemistry; D002021:Buffers; D002241:Carbohydrates / Q000737:chemistry; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry; D005029:Ethylenediamines / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry; D007476:Ionophores / Q000737:chemistry; D007477:Ions; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D013696:Temperature
D000438:Alcohols; D002021:Buffers; D002241:Carbohydrates; D004337:Drug Carriers; D005029:Ethylenediamines; D005079:Excipients; D005227:Fatty Acids; D007476:Ionophores; D007477:Ions; D010743:Phospholipids; D013501:Surface-Active Agents; C012571:tetronic 701; D011092:Polyethylene Glycols