Vranic, Branko Z.. Design of experiments methodology in studying near-infrared spectral information of model intact tablets : simultaneous determination of metoprolol tartrate and hydrochlorothiazide in solid dosage forms and powder compressibility assessment using near-infrared spectroscopy. 2015, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_11144
Simultaneous NIRS quantification of two APIs in powders and tablets requires several challenges to be overcome. Overlapping absorption peaks of formulation components result in method specificity problem. Strategy for selecting the samples used for developing the prediction models is needed. Robustness of the method towards formulation factors needs to be assessed due to complex formulation. Fast and simple method for simultaneous quantification of Hydrochlorothiazide (HTZ) and Metoprolol Tartrate (MTP) in powders and tablets was proposed in work. Simulation of industrial scale tablet machine using tablet press replicator - Presster® was proposed as fast and cost-effective alternative for design and manufacture of tablet sets needed for NIRS calibration model development. Balance Reference Method (BRM) was proposed as an alternative to HPLC and UV-spectroscopy which are traditionally used as reference methods in NIRS model development. The proposed experimental setup was suggested for the feasibility study stage of the method development. The two model drugs were simultaneously quantified using NIRS exhibiting RMSEP of 1.69 and 1.31 mg in HTZ powder and tablet samples respectively, while MTP powder and tablet samples were predicted with RMSEP of 3.15 and 3.00 mg respectively. NIRS analysis of Metoprolol Tartrate and Hydrochlorothiazide in powders and tablets was not yet reported in the literature.
The compressibility and compatibility of a powder formulation is conventionally determined by compaction followed by destructive tensile strength and relative density measurement of the final compact. In this study, a non-destructive near-infrared spectroscopic (NIRS) was evaluated for the determination of powder compressibility and compactibility. Twelve different formulations were investigated with 2 batches produced per formulation. Relative density and tensile strength were measured using a traditional, destructive method on one tablet batch and subsequently by a developed non-destructive chemometric NIRS method on the second batch of the particular formulation. The outcomes of the two approaches were compared to validate the developed method. All data sets were fitted to the three established mathematical equations to calculate equation factors, which represent a formulation compressibility and compactibility. The study focus was set on the equation factor comparison between the traditional and the newly designed method. The results have shown a high degree similarity between the outcomes of the two methods. A discrepancy between the two methods was observed for the outcomes of the equation factors after fitting to Leuenberger equation. The approach using NIRS is suggested as a promising tool for monitoring tablet manufacturing process.
|Advisors:||Hamburger, Matthias Otto|
|Committee Members:||Vandamme, Thierry F. and Huwyler, Jörg|
|Faculties and Departments:||05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Biologie (Hamburger)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||133 Bl.|
|Last Modified:||30 Jun 2016 10:57|
|Deposited On:||24 Mar 2015 15:14|
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