An effective and stability-indicating method development and optimization utilizing the Box-Behnken design for the...

Analytical techniques must be sensitive, specific, and accurate to assess the active pharmaceutical ingredients in pharmaceutical dosage forms. The quality-by-design (QbD) application has proven to be a practical method for magnifying HPLC operations. This article discusses the successfully developed QbD-based stability-indicative LC method for evaluating acetaminophen, caffeine, and aspirin (ASP) in tablet dosage form. To achieve the necessary chromatographic separation, Milli-Q water, methanol, and glacial acetic acid were employed in the following ratios: 63:35:2 (v/v/v) for mobile phase A and 18:80:2 (v/v/v) for mobile phase B. The flow rate, column temperature, and detecting wavelength were 1.0 ml/min, 40°C, and 275 nm, respectively, and an InertSustain C18 analytical column (150 × 4.6 mm, 3 μm) was used. Linearity was between 10.0 and 150.0 μg/ml for ASP and acetaminophen and between 2.6 and 39.0 μg/ml for caffeine. The accuracy findings were more than 97%, and the correlation coefficient for all three components was found to be greater than 0.999. The validated HPLC method yielded reliable and accurate results. ASP was shown to be vulnerable to both acid and alkaline hydrolysis in the forced degradation study. The described method is capable of separating the degradants produced during stress testing and is regarded as stability indicating. The proposed method can be used for a wider range of other formulations with an appropriate diluent selection and sample preparation procedure optimization.