Optimization of a forced degradation study of atorvastatin employing an experimental design approach

Abstract

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.

Development of a stability-indicating method for evaluation of impurity profile of Atorvastatin film-coated tablets using cyano column based on core-shell technology

“…The European Pharmacopoeia monograph of Atorvastatin calcium trihydrate 1 prescribes the HPLC method for impurities testing of atorvastatin active substance using an octylsilyl C8 column and a mobile phase composed of acetonitrile, tetrahydrofuran and ammonium acetate buffer adjusted to pH 5.0 with glacial acetic acid. There are also a few published HPLC analytical methods for the quantification of atorvastatin and its impurities using a C18 or C8 column, with tetrahydrofuran in the mobile phase composition, [15][16][17][18][19][20] which was to be avoided in our research due to its toxicity and instability. The method published by Vukkum 20 using simple gradient elution with 0.1 % trifluoroacetic acid and acetonitrile and a Zorbax Bonus RP column, reported good resolution between critical pairs in a short run time of 25 min.…”

“…As a hydrophobic molecule, mostly columns recommended for the evaluation of Atorvastatin impurity profile are C18 or C8. [15][16][17][18][19][20] However, the overlapping peaks co-eluting with impurity B during the predictive stability indicating experiments could not be separated using the commonly used methods on C8 and C18 columns.…”