Currently we dissolve it in minimal DMSO then add cremophore-EL. This mixture is then diluted in buffer immediately before injecting. It’s a struggle to keep the compound in solution it readily precipitates out. Any suggestions would be appreciated.
Dear PhD, a very good method to determine the best solvent for a solute is determined the polarity, using the contibucion method ferdors groups. Once one has the polarity of the solute is used a solvent or cosolvent mixture with similar polarity. [email protected]
Dear David,
You could try to delay precipitation by adding PVP (Polyvinylpyrrolidone) to your buffer. Up to 2% is safe for intravenous injection (in Humans) according to FDA's inactive ingredient database (link attached). It may help to keep your drug from crashing out when you dilute the stock prior to injection. See the other attached link for the precipitation inhibitory effect of a povidone on indomethacine.
A likely more efficient and easy way to avoid both supersaturation and subsequent precipitation is to adjust the pH of the diluent buffer. Norketamine has a pKa around 7.4 and will be considerably higher apparent soluble (~ 5 times if your current pH is 7.4) if you reduce the pH of the buffer one unit to 6.4.
Best regards / Jonas
http://www.ncbi.nlm.nih.gov/pubmed/24122167
http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm
Dear David,
you could try a polymer we are working with and could prepare extremely highly loaded and stable formulations of a number of drugs which otherwise crystallize easily, for example Paclitaxel.
http://www.sciencedirect.com/science/article/pii/S0142961210003030
http://pubs.acs.org/doi/abs/10.1021/mp300159u
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