Described is a device and method for facilitating the determination of the solubility and dissolution properties of chemical compounds in various solvents. The device uses submilliliter quantities of a solvent and correspondingly small amounts of the chemical compound. The device enables solubility measurements to be made on small amounts of chemical compounds, and enables multiple sampling for generating dissolution profiles. The device includes a housing having first chamber in fluid communication with a second chamber. A pump is provided to force alternatingly the solvent from one chamber to another. A filter located between, and in fluid communication with, the first and second chambers allows flow of a solution of the solvent and the chemical compound between the chambers, and the filter prevents the passage of undissolved compound. The device may also be used for titration studies of submilliliter quantities of solutions or suspensions.
This application claims the benefit of U.S. Provisional Application No. 60/042,698, filed Apr. 4, 1997, and titled "Device and Method for Measuring Solubility and for Performing Titration Studies of Submilliliter Quantities".
This invention relates to a method for the determination of solubility of a compound and an analytical device for carrying out said method. The basic method involves determining solubility of a compound by measuring the UV spectrum of a reference solution of the compound, under conditions avoiding or suppressing precipitation, and comparing it to the UV spectrum of a saturated sample solution of the compound. Variations of the basic method include: (a) making reference solutions either by dilution of the sample solution to the point where precipitation is avoided, or making reference solutions by adding a water-miscible cosolvent to the sample solution so that precipitation is suppressed, and comparing the UV absorbances of the compound under reference conditions to the compound in a saturated solution, (b) determining the true aqueous solubility from the effect on the pK.sub.a that results from dissolving the compound in an aqueous solution containing some DMSO (typically 0.1-5% v/v), and (c) correcting concentrations determined from the UV absorbance values for impurities and other factors that might affect the shape of the sample absorbance curve taken of the saturated solution.
Equipment and method of use for in vitro buccal dissolution testing. The invention is particularly useful for evaluating the effect of taste-masking in oral dosage forms.
The invention is a method and device for determining dissolution of a solid compound within the oral cavity. The device models dissolution within the oral cavity with a flow-through cell containing a solid compound and physiological amounts of simulated saliva. The device supplies and removes the simulated saliva at rates similar to production and loss of saliva within the oral cavity. The simulated saliva interaction with the solid compound mimics saliva interaction with a solid compound within the oral cavity. Dissolution of solid compound is determined from simulated saliva collected from the flow-through cell outflow.
Methods and systems for determining a dissolution profile of a sample material, and for solubilization screening of a library defined by an array comprising multiple sample materials are disclosed. The methods and systems are particularly advantageous for sampling and evaluation of very small samples, and can be advantageously applied in connection with evaluation of drug candidates.
