This manuscript describes comprehensive approach for assessment of degradation behavior of simvastatin employing experimental design methodology as scientific multifactorial strategy. Experimental design methodology was used for sample preparation and UHPLC method development and optimization. Simvastatin was subjected to stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic degradation. Using 2n full factorial design degradation conditions were optimized to obtain targeted level of degradation. Screening for optimal chromatographic condition was made by Plackett–Burman design and optimization chromatographic experiments were conducted according to Box-Behnken design. Successful separation of simvastatin from the impurities and degradation products was achieved on Poroshell 120 EC C18 50 × 3.0 mm 2.7 μm, using solutions of 20 mM ammonium formate pH 4.0 and acetonitrile as the mobile phase in gradient mode. The proposed method was validated according to International Conference on Harmonization (ICH) guidelines. Validation results have shown that the proposed method is selective, linear, sensitive, accurate, and robust and it is suitable for quantitative determination of simvastatin and its impurities. Afterwards, the degradation products were confirmed by a direct hyphenation of liquid chromatograph to ion-trap mass spectrometer with heated electrospray ionization interface. This study highlights the multiple benefits of implementing experimental design, which provides a better understanding of significant factors responsible for degradation and ensures successful way to achieve degradation and can replace the trial and error approach used in conventional forced degradation studies.

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.

Differential scanning calorimetry and Fourier transform infrared spectroscopy were applied as screening analytical methods to assess the solid-state compatibility of indapamide (4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoyl-benzamide) with several polymers aimed for development of 24 h sustained release solid-dosage formulation. After the initial research phase which was directed towards selection of suitable polymer matrices, based on their solid-state compatibility with the studied pharmaceutical active ingredient, the second phase of evaluation was intended for compatibility selection of other excipients required to complete a sustained release formulation. The preformulation studies have shown that polyvinylpyrrolydone/polyvinyl acetate might be considered incompatible with indapamide, and the implementation of this polymer career should be avoided in the case of the entitled development. The experimental data additionally have revealed that sorbitol is incompatible with indapamide. The obtained results afforded deeper insight in to the solid-state stability of the studied binary systems and pointed out directions for further development of indapamide sustained release solid-dosage formulation.

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.

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