title: Evaluation of drug load and polymer by using a 96-well plate vacuum dry system for amorphous solid dispersion drug delivery.
abstract: It is well recognized that poor dissolution rate and solubility of drug candidates are key limiting factors for oral bioavailability. While numerous technologies have been developed to enhance solubility of the drug candidates, poor water solubility continuously remains a challenge for drug delivery. Among those technologies, amorphous solid dispersions (SD) have been successfully employed to enhance both dissolution rate and solubility of poorly water-soluble drugs. This research reports a high-throughput screening technology developed by utilizing a 96-well plate system to identify optimal drug load and polymer using a solvent casting approach. A minimal amount of drug was required to evaluate optimal drug load in three different polymers with respect to solubility improvement and solid-state stability of the amorphous drug-polymer system. Validation of this method was demonstrated with three marketed drugs as well as with one internal compound. Scale up of the internal compound SD by spray drying further confirmed the validity of this method, and its quality was comparable to a larger scale process. Here, we demonstrate that our system is highly efficient, cost-effective, and robust to evaluate the feasibility of spray drying technology to produce amorphous solid dispersions.
authors.affiliation: Global Research and Development, SMPS, Genentech Inc., 1 DNA Way, South San Francisco, California 4080, USA. Chiang.pochang@gene.com
authors.forename: Po-Chang
authors.initials: PC
authors.lastname: Chiang
authors.forename: Yingqing
authors.initials: Y
authors.lastname: Ran
authors.forename: Kang-Jye
authors.initials: KJ
authors.lastname: Chou
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.forename: Amy
authors.initials: A
authors.lastname: Sambrone
authors.forename: Connie
authors.initials: C
authors.lastname: Chan
authors.forename: Ryan
authors.initials: R
authors.lastname: Hart
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D000068579:Celecoxib; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004337:Drug Carriers; D004355:Drug Stability; D004867:Equipment Design; D006118:Griseofulvin / Q000737:chemistry; D057166:High-Throughput Screening Assays / Q000295:instrumentation* / Q000592:standards; D065347:Hypromellose Derivatives; D007213:Indomethacin / Q000737:chemistry; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008904:Miniaturization; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D011720:Pyrazoles / Q000737:chemistry; D011786:Quality Control; D015203:Reproducibility of Results; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods / Q000592:standards; D014618:Vacuum; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D011108:Polymers; D011720:Pyrazoles; D012997:Solvents; D013449:Sulfonamides; D014867:Water; D006118:Griseofulvin; D000082:Acetaminophen; D065347:Hypromellose Derivatives; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose; D011205:Povidone; D000068579:Celecoxib; D007213:Indomethacin