JABLONSKA, Wioletta (2011). The use of ATR-FTIR to probe the release mechanism from hydrophilic matrices. Doctoral, Sheffield Hallam University.
Jablonska_use_of_ATR-FTIR.pdf - Accepted Version
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Hydrophilic matrices are widely used in the pharmaceutical industry as control release agents in solid oral dosage formulations. One of the key parameters that controls release in such systems is the distribution of exipients within the formulation, which in turn is governed by the processing and manufacturing procedures. This thesis explores the effect of processing on the distribution of excipients in binary and tertiary formulations obtained using different mixing procedures, (manual shaking, tumble blending and grinding) with a range of particle size distributions. Samples were prepared by compacting processed powder mixtures directly onto a diamond attenuated total reflectance (ATR) crystal using an in-house built compaction cell which proved to be a successful tool for small scale tablet manufacturing. For this study the following exipients were used; the hydrophilic matrix HPMC grade K4M, the drug 6-hydroxy buspirone hydrochloride and citric acid. The homogeneity of the formulations were determined by the reproducibility of the spectra obtained from the tablets after compaction and the concentration of exipients within the samples was successfully predicted using Partial Least Squares (PLS) data analysis. The distribution of the components was confirmed using Near Infrared imaging with principal components analysis (PCA). Standard dissolution tests of the binary and tertiary systems gave an indication about the release behaviour of the formulations in different dissolution media. Total dissolution of the drug was observed in 0.1N HCl for binary mixtures and in both pH 6.8 buffer and 0.1 N HCl for tertiary formulations highlighting the impact of citric acid on the dissolution results and confirming the pH dependence of the system. The release of drug was also studied using the complementary technique of ATR-FTIR by performing hydration experiments on the compacted tablets. Both standard data analysis approaches, such as peak area changes, and multivariate curve resolution (MCR) were applied to these datasets. The MCR studies showed some promise, but also highlighted a need for further development. The standard data analysis showed that the rate of release of the API and citric acid was higher than the rate of solvation of HPMC, indicating a diffusion controlled release mechanism. Standard dissolution experiments and infrared spectroscopy measurements were combined, by developing a hyphenated system, whereby dissolution media was circulated through the ATR compaction cell and out through a UV/vis flow detector in a closed loop. These results were in good agreement with the data from both the standard dissolution tests and the ATR-FTIR hydration studies.
|Item Type:||Thesis (Doctoral)|
|Research Institute, Centre or Group:||Sheffield Hallam Doctoral Theses|
|Depositing User:||Helen Garner|
|Date Deposited:||28 Aug 2013 15:15|
|Last Modified:||19 Aug 2015 17:36|
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