Evaluation of Drug Load and Polymer by Using a 96-Well Plate Vacuum Dry System for Amorphous Solid Dispersion Drug Delivery

• Published in: AAPS PharmSciTech Vol. 13; no. 2; pp. 713 - 722
• Main Authors: Chiang, Po-Chang, Ran, Yingqing, Chou, Kang-Jye, Cui, Yong, Sambrone, Amy, Chan, Connie, Hart, Ryan
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.06.2012
• Subjects: Acetaminophen - chemistry; Bioavailability; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Celecoxib; Chemistry, Pharmaceutical; Crystallization; Dissolution; Drug Carriers; Drug delivery; Drug development; Drug Stability; Drying; Equipment Design; Griseofulvin - chemistry; high-throughput screening; High-Throughput Screening Assays - instrumentation; High-Throughput Screening Assays - standards; Hypromellose Derivatives; Indomethacin - chemistry; Kinetics; Limiting factors; Methylcellulose - analogs & derivatives; Methylcellulose - chemistry; Miniaturization; Pharmaceutical Preparations - chemistry; Pharmacology/Toxicology; Pharmacy; Polymers - chemistry; Povidone - chemistry; Pyrazoles - chemistry; Quality Control; Reproducibility of Results; Research Article; Solubility; Solvents; Solvents - chemistry; Sulfonamides - chemistry; Technology, Pharmaceutical - instrumentation; Technology, Pharmaceutical - methods; Technology, Pharmaceutical - standards; Vacuum; Water - chemistry; SD; SDD; amorphous; 96-well; bioavailability; HTPs; solid dispersions; spray dry
• DOI: 10.1208/s12249-012-9795-2
• ISSN: 1530-9932

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.