title: Solvent shift method for anti-precipitant screening of poorly soluble drugs using biorelevant medium and dimethyl sulfoxide.
abstract: 96-well plate based anti-precipitant screening using bio-relevant medium FaSSIF (fasted-state simulated small intestinal fluid) is a useful technique for discovering anti-precipitants that maintain supersaturation of poorly soluble drugs. In a previous report, two disadvantages of the solvent evaporation method (solvent casting method) were mentioned: precipitation during the evaporation process and the use of volatile solvents to dissolve compounds. In this report, we propose a solvent shift method using DMSO (dimethyl sulfoxide). Initially, the drug substance was dissolved in DMSO at a high concentration and diluted with FaSSIF that contained anti-precipitants. To evaluate the validity of the method, itraconazole (ITZ) was used as the poorly soluble model drug. The solvent shift method resolved the disadvantages of the evaporation method, and AQOAT (HPMC-AS) was found as the most appropriate anti-precipitant for ITZ in a facile and expeditious manner when compared with the solvent evaporation method. In the large scale JP paddle method, AQOAT-based solid dispersion maintained a higher concentration than Tc-5Ew (HPMC)-based formulation; this result corresponded well with the small scale of the solvent shift method.
authors.affiliation: Analytical Research, CMC Japan, Pharmaceutical Science & Technology Core Function Unit, Eisai Product Creation Systems, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan. t5-yamashita@hhc.eisai.co.jp
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ozaki
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kushida
mesh_terms: D011232:Chemical Precipitation; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D057166:High-Throughput Screening Assays / Q000379:methods; D007419:Intestinal Secretions / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D017964:Itraconazole / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*
chemical_list: D012997:Solvents; D017964:Itraconazole; D004121:Dimethyl Sulfoxide