Xue-Qing Chen1, Srini Venkatesh. 1. Discovery Pharmaceutics, Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA. xue-qing.chen@bms.com
Abstract
PURPOSE: A miniature device was developed for the measurement of aqueous and non-aqueous equilibrium solubility during drug discovery. The solubility values obtained using the miniature device were compared to those obtained using the conventional shake-flask method. METHODS: The aqueous solubility of six structurally diverse compounds, the solubility of carbamazepine in various cosolvent systems, and the pH-solubility profile of saquinavir were determined using the miniature device. The device contains a multichannel cartridge pump and a Tygon tubing that is mounted on the pump with two ends linked by a syringe filter. The drug slurry was filled into the tubing and circulated inside, continually passing through the syringe filter. At the end of the experiment, the filtrate was collected and analyzed directly by High-Pressure Liquid Chromatography (HPLC). The solubility was also determined by the shake-flask method. RESULTS: The solubility values determined by the miniature device were in good agreement with those measured by the conventional shake-flask method. CONCLUSIONS: The miniature device provides a unique way of testing aqueous and non-aqueous equilibrium solubility in a microscale setting. With approximately 1 mg of compound, it is possible to determine the entire pH-solubility profile. The device is useful for solubility screening during lead optimization and candidate selection in early drug discovery, when compound supply is limited. It can also be used for screening solubility in non-aqueous systems to select vehicles for preclinical in vivo studies.
PURPOSE: A miniature device was developed for the measurement of aqueous and non-aqueous equilibrium solubility during drug discovery. The solubility values obtained using the miniature device were compared to those obtained using the conventional shake-flask method. METHODS: The aqueous solubility of six structurally diverse compounds, the solubility of carbamazepine in various cosolvent systems, and the pH-solubility profile of saquinavir were determined using the miniature device. The device contains a multichannel cartridge pump and a Tygon tubing that is mounted on the pump with two ends linked by a syringe filter. The drug slurry was filled into the tubing and circulated inside, continually passing through the syringe filter. At the end of the experiment, the filtrate was collected and analyzed directly by High-Pressure Liquid Chromatography (HPLC). The solubility was also determined by the shake-flask method. RESULTS: The solubility values determined by the miniature device were in good agreement with those measured by the conventional shake-flask method. CONCLUSIONS: The miniature device provides a unique way of testing aqueous and non-aqueous equilibrium solubility in a microscale setting. With approximately 1 mg of compound, it is possible to determine the entire pH-solubility profile. The device is useful for solubility screening during lead optimization and candidate selection in early drug discovery, when compound supply is limited. It can also be used for screening solubility in non-aqueous systems to select vehicles for preclinical in vivo studies.
Authors: Daniela Hartmann Jornada; Guilherme Felipe dos Santos Fernandes; Diego Eidy Chiba; Thais Regina Ferreira de Melo; Jean Leandro dos Santos; Man Chin Chung Journal: Molecules Date: 2015-12-29 Impact factor: 4.411