This study involved the optimization of experimental conditions for the forced degradation of atorvastatin employing the experimental design (DoE) approach, as a scientific multifactorial strategy. Using 2n full factorial design, stress conditions of oxidative, hydrolytic and thermal degradation were optimized to obtain a targeted level of atorvastatin degradation. Atorvastatin and all related and degradation products were separated on Poroshell 120 EC C18 50 ´ 3.0 mm 2.7 μm, using 10 mM ammonium formate and acetonitrile as mobile phases in the gradient mode. The impurity structures were confirmed by the direct hyphenation of a liquid chromatograph to an ion trap mass spectrometer with a heated electrospray ionization interface.This study highlights the multifold benefits of implementing the DoE concept, which provides a better understanding of the significant factors responsible for degradation and ensures a successful way to achieve degradation, thereby replacing the trial and error approach used in conventional forced degradation studies.

The release model of the optimized formulation has shown best fit to the zero order kinetics depicted with the Hixson-Crowell erosion-dependent mechanism of release. Level A correlation was obtained.

This manuscript presents chemometrically assisted optimization and validation of UPLC method intended for the quantitative analysis of simvastatin in pharmaceutical preparations. To achieve the desired chromatographic response and to simultaneously optimize the most important chromatographic parameters with a limited number of experiments in a minimum amount of time, Box-Behnken design was used. The separation was performed on Poroshell 120 EC C18 50 x 3.0 mm 2.7 μm, using 10 mM ammonium formate pH 4.0 and acetonitrile as the mobile phase. To obtain complete information about method performance and robustness, seven factors (column type, acetonitrile content, temperature, pH of mobile phase, molarities of ammonium formate, flow rate and wavelength) were assessed in twelve experiments according to Plackett–Burman design. The proposed method was validated according to International Conference on Harmonization (ICH) guidelines to confirm specificity, linearity, precision, detection and quantification limits. Validation results have shown that the proposed method is selective, linear, accurate, sensitive (LOD 0.06 μg/mL and LOQ 0.18 μg/mL), and robust and it is suitable for quantitative determination of simvastatin in pharmaceutical preparations. The optimized and validated method gives rapid and efficient separation and represents an improvement over the existing methods especially in the terms of sensitivity, low cost of analysis per sample and the environmental impact of the method. Keywords: chemometry, design of experiments, UPLC/DAD, simvastatin

Dissolution testing is an essential tool in the pharmaceutical industry and is used in formulation and process development, in monitoring of the manufacturing process, as a quality control test, to predict the in vivo performance. The purpose of this study is to evaluate the behaviour of the test and reference products using conventional dissolution apparatus basket and paddle, with tendency to evaluate the dependence of the in vitro dissolution of the dissolution test conditions (dissolution apparatus, medium, agitation, pH). Experimental design (ED) approach has been employed for assessment of the discriminatory properties of different dissolution conditions. The responses statistically evaluated were: f 2 similarity factor and the difference in the dissolution rate between the test and reference product, expressed in percentage, at every time point. Furthermore, this study focusses on developing a statistically reliable mathematical model for predicting discriminatory experimental conditions.