Determination of the Optimum Settings of a Fibrous Loose-Fill Blowing Machine Using Design of Experiments

Development of HPLC Method for the Purity Test by Design of Experiments and Determination of Activation Energy of Hydrolytic Degradation Reactions of Sofosbuvir

Current Pharmaceutical Analysis ◽

10.2174/1573412915666190225161007 ◽

2020 ◽

Vol 16 (7) ◽

pp. 976-987

Author(s):

Jakub Petřík ◽

Jakub Heřt ◽

Pavel Řezanka ◽

Filip Vymyslický ◽

Michal Douša

Keyword(s):

Activation Energy ◽

Design Of Experiments ◽

Mobile Phase ◽

Hydrolytic Degradation ◽

Isoconversional Method ◽

Hplc Method ◽

Organic Modifier ◽

Calculation Methods ◽

Degradation Reactions

Background: The present study was focused on the development of HPLC method for purity testing of sofosbuvir by the Design of Experiments and determination of the activation energy of hydrolytic degradation reactions of sofosbuvir using HPLC based on the kinetics of sofosbuvir degradation. Methods: Following four factors for the Design of Experiments were selected, stationary phase, an organic modifier of the mobile phase, column temperature and pH of the mobile phase. These factors were examined in two or three level experimental design using Modde 11.0 (Umetrics) software. The chromatographic parameters like resolution, USP tailing and discrimination factor were calculated and analysed by partial least squares. The chromatography was performed based on Design of Experiments results with the mobile phase containing ammonium phosphate buffer pH 2.5 and methanol as an organic modifier. Separation was achieved using gradient elution on XBridge BEH C8 at 50 °C and a flow rate of 0.8 mL/min. UV detection was performed at 220 nm. The activation energy of hydrolytic degradation reactions of sofosbuvir was evaluated using two different calculation methods. The first method is based on the slope of dependence of natural logarithm of the rate constant on inverted thermodynamic temperature and the second approach is the isoconversional method. Results and Conclusion: Calculated activation energies were 77.9 ± 1.1 kJ/mol for the first method and 79.5 ± 3.2 kJ/mol for the isoconversional method. The results can be considered to be identical, therefore both calculation methods are suitable for the determination of the activation energy of degradation reactions.

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Software-guided microscale flow calorimeter for efficient acquisition of thermokinetic data

Journal of Flow Chemistry ◽

10.1007/s41981-021-00145-6 ◽

2021 ◽

Author(s):

Timothy Aljoscha Frede ◽

Marlene Dietz ◽

Norbert Kockmann

Keyword(s):

Design Of Experiments ◽

Process Development ◽

Reaction Conditions ◽

Experimental Conditions ◽

Flow Calorimeter ◽

Microscale Flow ◽

Increased Sensitivity ◽

Important Time ◽

Optimal Reaction

AbstractFast chemical process development is inevitably linked to an optimized determination of thermokinetic data of chemical reactions. A miniaturized flow calorimeter enables increased sensitivity when examining small amounts of reactants in a short time compared to traditional batch equipment. Therefore, a methodology to determine optimal reaction conditions for calorimetric measurement experiments was developed and is presented in this contribution. Within the methodology, short-cut calculations are supplemented by computational fluid dynamics (CFD) simulations for a better representation of the hydrodynamics within the microreactor. This approach leads to the effective design of experiments. Unfavourable experimental conditions for kinetics experiments are determined in advance and therefore, need not to be considered during design of experiments. The methodology is tested for an instantaneous acid-base reaction. Good agreement of simulations was obtained with experimental data. Thus, the prediction of the hydrodynamics is enabled and the first steps towards a digital twin of the calorimeter are performed. The flow rates proposed by the methodology are tested for the determination of reaction enthalpy and showed that reasonable experimental settings resulted. Graphical abstract A methodology is suggested to evaluate optimal reaction conditions for efficientacquisition of kinetic data. The experimental design space is limited by thestepwise determination of important time scales based on specified input data.

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