An improved method to prepare an injectable microemulsion of the galanin-receptor 3 selective antagonist, SNAP 37889, using Kolliphor® HS 15

Research into the galanin-3 (GAL3) receptor has many challenges, including the lack of commercially available selective ligands. While the identification of non-peptidergic GAL3 receptor-selective antagonists, 1-phenyl-3-[3-(trifluoromethyl)phenyl]iminoindol-2-one (SNAP 37889) and 1-[3-(2-pyrrolidin-1-ylethoxy)phenyl]-3-[3-(trifluoromethyl)phenyl]iminoindol-2-one (SNAP 398299) have implicated a role for GAL3 receptors in anxiety, depression and drug-seeking behaviour, a major limitation of their use is poor aqueous solubility. Previously we have used 5% dimethylsulfoxide (DMSO) with 1% hydroxypropylmethyl cellulose in saline to dissolve SNAP 37889 for intraperitoneal (i.p.) injections of rats; however this produced a micro-suspension that was not ideal. The injectable formulation of SNAP 37889 was improved as follows:
• 30% (w/v) Kolliphor® HS 15 (Solutol HS® 15) and sodium phosphate buffer (0.01 M, pH 7.4) were used as vehicles.
• A smooth glass mortar and pestle was used to triturate the Kolliphor® HS 15 and SNAP 37889 into a paste before addition to the sodium phosphate buffer at room temperature (RT).
• The resulting mixture was vortexed until the paste was fully dissolved and the microemulsion was allowed to sit for 20 min to allow air bubbles to coalesce.

Figure optionsDownload as PowerPoint slide