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

摘要

class="kwd-title">Keywords: Injectable microemulsion of SNAP 37889 class="kwd-title">Keywords: Galanin-3 receptor, Galanin-3 antagonist, SNAP 37889, Kolliphor^® HS 15, Solubility, i.p. injection, Drug delivery, Microemulsion class="head no_bottom_margin" id="idm140403003205264title">AbstractResearch 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: class="first-line-outdent">

• 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.