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Characterization of pharmaceutical formulations, functional polymers and counterfeit medicines using broadband acoustic reasonance dissolution spectroscopy
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Date
2019
Authors
Alfarsi, Anas
Journal Title
Journal ISSN
Volume Title
Publisher
University College Cork
Published Version
Abstract
The research herein represents a significant advance on the characterization of pharmaceutical formulations, through faster, more efficient, greener, and real-time solutions. The methods developed using broadband acoustic resonance dissolution spectroscopy (BARDS) have the potential to revolutionize key test requirements such as dissolution testing which is a cornerstone of the pharmaceutical industry. Not only this, the research also outlines how BARDS technology can be used to track new application areas such as coating thickness, disintegration, deaggregation, and coating integrity. Chapter 3 highlights new investigations where the sub-coating of pellet formulations can be tracked from 0-10 µm. This is followed by establishing a linear relationship between key features of a BARDS plot and the enteric coating thickness. This development in capability allows for a new approach to coating end point determination in industry.
BARDS technology is based on a reproducible acoustic resonance frequency change during the dissolution of a substance in fixed volume of a solution. These changes in resonant frequency occur due to the changes in the solution compressibility during the dissolution process. The addition of a sample will lead to gas entertainment in the solution. Also, the dissolution of the sample will reduce the solubility of the dissolved gases in the solution significantly leading to bubbles formation. The generation of gas bubbles will affect the compressibility of the solution, thus, reducing_ the sound frequency that is generated and monitored in the BARDS vessel. This BARDS phenomenon is unique to the sample tested at known concentration and its dependant on the physical and chemical properties of the sample.
In this research, BARDS technology was used to monitor the loading of enteric coating layers at different manufacturing stages of Omeprazole pellets. BARDS data correlates directly with the thickness of the enteric coating measured by scanning electron microscopy and coating integrity is validated by HPLC.
The taste masking polymer loading of the coating process was investigated by testing caffeine pellets via BARDS technology. Eudraguard® protect and Eudragit® E PO are the two types of coating polymer formulations investigated in this study. The technique offers a rapid approach to characterising functional coatings during their application such as integrity and thickness. BARDS data is indicative of the coating layer thickness assuming that the quality of the film coating is high. BARDS represents a possible future surrogate test for in-process control (IPC) testing, as a process analytical technology (PAT) method and maybe also for conventional United States Pharmacopeia (USP) dissolution testing. BARDS data correlate directly with the thickness of the functional coating, its integrity and also with the drug loading as validated by UV-Vis spectroscopy and scanning electron macroscopy.
The use of BARDS to discriminate between genuine and counterfeit medicine was also investigated. Results show the ability of the technology to differentiate between genuine and fake medicines. BARDS analysis were performed on different pharmaceutical formulations such as antimalarial Artesunate tablets, Panadol Extra, Zentel, Alli, Clamoxyl, and Betnovate creams. This represents a rapid and simple approach to screen suspect medicines using genuine medicine as a reference control.
Also, in this research the effect of Triton X-100 surfactant on BARDS outgassing process was investigated: The data show the potential of BARDS to be used as a nonoptical method to characterise the effect of surfactant on ascending bubbles.
In summary, these new applications of this innovation have been demonstrated with opportunity for more to be created. From this work BARDS analysis shows its potential to provide a solution for some of the challenges that impact the production of pharmaceutical products.
Description
Keywords
Broadband acoustic resonance dissolution spectroscopy , BARDS
Citation
Alfarsi, A. 2019. Characterization of pharmaceutical formulations, functional polymers and counterfeit medicines using broadband acoustic reasonance dissolution spectroscopy. PhD Thesis, University College Cork.