High Throughput Salt Profiling
Development of BCS type II compounds is an increasingly important challenge because the exposure is limited by solubility/dissolution. For ionizable molecules, the earliest approach to solve these problems should be by salt formation. The main scope of the early Salt Profiling is to identify a preliminary crystalline salt to support PK studies in Research and to achieve maximum exposure for the CSP Phase TOX studies. Salt Profiling is performed on a limited amount of drug substance, typically 200-300mg available from Research. The low purity of the early Research batches may hinder crystallization of salts and crystalline forms and, as such, a broad screening and full characterization of salts cannot, typically, be performed in this stage. In this screening method, salt formation by solvent evaporation is utilized. Selected “hits from the salt screen are evaluated on a larger scale and their physicochemical properties investigated. A chosen salt form, having higher solubility and faster dissolution rate than the free compound, that is physically and chemically stable should be subjected to pharmacokinetic studies in rodent or non rodent animal models. This presentation outlines High Throughput (HT) salt screening method for New Chemical Entities (NCE’s) using a minimum amount of compound (200-300 mg) and is intended to give a general introduction for salt formation, selection of counter-ions and solvents and to describe the basic procedure for utilizing the Crissy platform and other instrumentation for liquid dispensing, mixing and analysis of new solid forms.
Ren Guobin
Chemical & Pharmaceutical Profiling (CPP), China Novartis Institutes for BioMedical Research Co., Ltd. (CNIBR), Shanghai, China
国际会议
International Symposium on Crystal Engineering and Drug Delivery System 2009(2009晶体工程与药物传送系统国际会议)
天津
英文
170
2009-09-05（万方平台首次上网日期，不代表论文的发表时间）