Determination of drug dissolution using a quartz crystal microbalance
2014 American Association of Pharmaceutical Scientists Annual Meeting and Exposition
San Diego, CA
November 2-6, 2014
Date of Presentation
Purpose To develop a method to determine drug dissolution using micrograms of a sample. Methods Benzoic acid was dissolved in isopropyl alcohol and 150 μg of benzoic acid was deposited on a quartz crystal. After evaporation of the solvent, the quartz crystal was loaded onto the quartz crystal microbalance (QCM) with an attached flow-through cell and deionized water was used as the dissolution medium at the flow rates of 1000, 100, and 10 μL/min. As the benzoic acid was dissolved by the deionized water, the QCM measured the change in resonance frequency due to the change in mass. Using a 100 millisecond gate-time, the sensitivity of the QCM is 18 ng/cm2. With the corresponding change in frequency (and therefore mass), the dissolution rate of the sample was determined. Results Dissolution profiles from the dissolution of benzoic acid using a flow of deionized water on a QCM exhibit a mass loss profile that is similar to current methods. Additionally, decreasing the flow rate of the solvent decreases the rate of dissolution, resulting in average dissolution rates of 4.09x10-2, 5.80x10-3, and 1.25x10-3 mol/h using 1000, 100, and 10 μL/min flow rates respectively. The dissolution profiles exhibit a decrease in dissolution rate with decreased hydrodynamic forces. The profile is similar to current standardized methods. Conclusion The feasibility of using a QCM to determine the dissolution rate is demonstrated. The sample requirement for the determination of dissolution rate is at the microgram scale and the time requirement is well-within an hour. It is observed that a QCM can be used to find the dissolution rate of drugs in as little as 2 minutes. With the QCM being sensitive to mass changes of 18 ng/cm2, this method requires only several hundred micrograms of sample per trial, which is several orders below that of current methods.
Bonoan, J. A.,
Determination of drug dissolution using a quartz crystal microbalance.
Paper presented at 2014 American Association of Pharmaceutical Scientists Annual Meeting and Exposition in San Diego, CA.