Determining the suitability of mass spectrometry for understanding the dissolution processes involved with pharmaceutical tablets

Lewis, C. and Ray, A. and Bristow, T. and Wren, S. (2015) Determining the suitability of mass spectrometry for understanding the dissolution processes involved with pharmaceutical tablets. Rapid Communications in Mass Spectrometry, 29 (12). pp. 1107-1114. ISSN 1097-0231

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Abstract

RATIONALE: A current challenge for analytical chemists is the development of measurement systems and approaches required to understand dynamic processes such as tablet dissolution. The design and development of oral tablets could be improved by the availability of detailed information about the rates of release of the individual tablet components. Small footprint mass spectrometry (MS) systems are gaining use for on-line reaction monitoring because of their ability to rapidly determine multiple reactant, intermediate, and product species. We have therefore assessed the utility of such MS systems to the study of dissolution processes.

METHODS: Aqueous dissolution media containing phosphate and other non volatile buffer salts were pumped from a standard USPII dissolution vessel through an active splitter and back. The splitter sampled the dissolution stream and diluted it into a make-up flow which was pumped to a small single quadrupole mass spectrometer. Single ion monitoring was used to quantify the ions of interest. Three different bio-relevant dissolution media were studied to gauge the impact of the sample matrix.

RESULTS: Individual dissolution profiles were obtained from a tablet containing three drugs and lactose as the soluble filler. This was successfully demonstrated with three different bio-relevant media designed to reflect the pH of the different sections of the human gastro-intestinal tract. Component concentrations as low as 0.06 μg/mL (representing 1% dissolution) were detected. The MS dissolution profiles correlated with the visual observation of tablet dissolution. MS gave linear responses with concentration for the individual components, although analysis of the tablet solution indicated that ion suppression is an area for further investigation

CONCLUSIONS: An on-line MS system was used to determine the individual dissolution profiles of three drugs and lactose as they are released from the same tablet. The level of each of these components in solution was determined every 10 seconds, and each had a similar release profile. The dissolution profiles were determined using inorganic buffer solutions at three different bio-relevant pHs.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: C.Lewis, A. Ray, T. Bristow, S. Wren. Determining the suitability of mass spectrometry for understanding the dissolution processes involved with pharmaceutical tablets. Rapid Commun. Mass Spectrom. 2015,29,1107-1114, which has been published in final form at doi: 10.1002/rcm.7203. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Schools/Departments: University of Nottingham UK Campus > Faculty of Science > School of Pharmacy
Identification Number: https://doi.org/10.1002/rcm.7203
Depositing User: Lewis, Claire
Date Deposited: 10 Sep 2015 08:50
Last Modified: 17 Sep 2016 10:59
URI: http://eprints.nottingham.ac.uk/id/eprint/29883

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