An effective and stability‐indicating method development and optimization utilizing the Box–Behnken design for the simultaneous determination of acetaminophen, caffeine, and aspirin in tablet formulation

Abstract

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.

Separation and quantitative estimation of stereo‐selective enantiomers of montelukast in pharmaceutical drug substance and tablets dosage forms by using stability‐indicating normal phase‐HPLC method

“…In the interest of optimizing the method, the experiments were conducted in a variety of trials utilizing various mobile phases, columns, and other chromatographic conditions 10–31 . The following is a summary of all the trials.…”

“…The stress testing discloses process‐related impurities, degradation‐related products, degradation pathways, and intrinsic stability 10–30 . The stability‐indicating characteristics of the proposed NP‐HPLC method was evaluated as follows using the stressed sample solution of 1.2 mg/mL.…”

“…As a result, the authors aimed to develop a new normal phase high‐performance liquid chromatography (NP‐HPLC) method for the separation and quantitative detection of the S‐enantiomer of montelukast in both pharmaceutical drug substance and drug products. The stability‐indicating characteristics of the developed NP‐HPLC method were proven through the stress testing studies, as all the peaks obtained from the placebo, solvents of the diluent or mobile phase, montelukast, and its other eight known impurities were separated well from each other without any interference 10–31 . The newly developed NP‐HPLC method was also capable of estimating the amount of the enantiomers of sulfoxide impurities (sulfoxide 1 impurity: R‐isomer, and sulfoxide 2 impurity: S‐isomer) in the MLS drug substance and formulated tablet dosage forms.…”

Separation and quantitation of valacyclovir enantiomers using stability‐indicating chiral liquid chromatography method with a chiral stationary phase of amylose tris‐(3,5‐dimethylphenylcarbamate)

“…The forced degradation study aids in the development of a stability‐indicating liquid chromatographic method and provides information regarding the drug moiety's intrinsic stability, impurity profile (process‐related impurities or degradation‐related products), and degradation pathways [27–50].…”

“…The authors, thus, focused on developing a new stability‐indicating method employing normal‐phase HPLC for the separation and estimation of D‐Valacyclovir impurity in the Valacclovir drug substance and drug product [27–50]. The chromatographic peaks obtained from placebo (a blend of excipients used in formulation) and diluent, as well as all 14 known impurities, were resolved very well from both the valacyclovir and D‐Valacyclovir.…”