Development of an Innovative Quality by Design (QbD) Based Stability-Indicating HPLC Method and its Validation for Clofazimine from its Bulk and Pharmaceutical Dosage Forms

Patil, Tulshidas S.; Deshpande, Ashwini

doi:10.1007/s10337-018-3660-8

Cited by 26 publications

(6 citation statements)

References 14 publications

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“…For the lipophilic antibiotic CFZ, a reduction by 32% was detected, which is probably due to the indirect effect of irradiation, that is, the production of reactive oxygen species. This observation is in accordance with a previous study, where CFZ was shown to be prone to degradation under oxidative stress conditions, resulting in 35.56% CFZ degradation ( 39 ). Importantly, regarding the distribution of CFZ, no irradiation-induced changes were observed by MALDI-MS imaging.…”

Section: Discussionsupporting

confidence: 94%

Interleukin-13-Overexpressing Mice Represent an Advanced Preclinical Model for Detecting the Distribution of Antimycobacterial Drugs within Centrally Necrotizing Granulomas

Walter

Kokesch-Himmelreich

Treu

et al. 2022

Antimicrob Agents Chemother

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The Mycobacterium tuberculosis (Mtb)-harboring granuloma with a necrotic center surrounded by a fibrous capsule is the hallmark of tuberculosis (TB). For a successful treatment, antibiotics need to penetrate these complex structures to reach their bacterial targets. Hence, animal models reflecting the pulmonary pathology of TB patients are of particular importance to improve the pre-clinical validation of novel drug candidates. Mtb-infected interleukin-13 overexpressing (IL-13 tg ) mice develop a TB pathology very similar to patients and, in contrast to other mouse models, also share pathogenetic mechanisms. Accordingly, IL-13 tg animals represent an ideal model for analyzing the penetration of novel anti-TB drugs into various compartments of necrotic granulomas by matrix-assisted-laser-desorption/ionization-mass spectrometry imaging (MALDI MS imaging). In the present study, we evaluated the suitability of BALB/c IL-13 tg mice for determining the antibiotic distribution within necrotizing lesions. To this end, we established a workflow based on the inactivation of Mtb by gamma irradiation while preserving lung tissue integrity and drug distribution, which is essential for correlating drug penetration with lesion pathology. MALDI MS imaging analysis of clofazimine, pyrazinamide and rifampicin revealed a drug-specific distribution within different lesion types including cellular granulomas, developing in BALB/c wild-type mice, and necrotic granulomas of BALB/c IL-13 tg animals, emphasizing the necessity of pre-clinical models reflecting human pathology. Most importantly, our study demonstrates that BALB/c IL-13 tg mice recapitulate the penetration of antibiotics into human lesions. Therefore, our workflow in combination with the IL-13 tg mouse model provides an improved and accelerated evaluation of novel anti-TB drugs and new regimens in the pre-clinical stage.

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Section: Discussionsupporting

confidence: 94%

Interleukin-13-Overexpressing Mice Represent an Advanced Preclinical Model for Detecting the Distribution of Antimycobacterial Drugs within Centrally Necrotizing Granulomas

Walter

Kokesch-Himmelreich

Treu

et al. 2022

Antimicrob Agents Chemother

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“…The statistical data set was further evaluated for parameters such as correlation coefficient ( R 2 ), adjusted correlation coefficient (adjusted R 2 ), predicted correlation coefficient (predicted R 2 ), and precision. Utilizing the response surface methodology (RSM) model, as elucidated by Patil and Deshpande (2019) graphical representations such as 2D contour plots and 3D response surfaces were generated. Subsequently, the optimized chromatographic method was integrated within the defined “design space.” Please refer to Figures 4 and 5 for details.…”

Section: Resultsmentioning

confidence: 99%

Development of a novel quality by design–enabled stability‐indicating HPLC method and its validation for the quantification of nirmatrelvir in bulk and pharmaceutical dosage forms

Alegete,

Byreddy

2024

Biomedical Chromatography

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A systematic and novel quality by design–enabled, rapid, simple, and economic stability–indicating HPLC method for quantifying nirmatrelvir (NMT) was successfully developed and validated. An analytical target profile (ATP) was established, and critical analytical attributes (CAAs) were allocated to meet the ATP requirements. The method used chromatographic separation using a Purosphere column with a 4.6 mm inner diameter × 250 mm (2.5 μm). The analysis occurred at 50°C with a flow rate of 1.2 mL/min and detection at 220 nm. A 10 μL sample was injected, and the mobile phase consisted of two components: mobile phase A, containing 0.1% formic acid in water (20%), and mobile phase B, containing 0.1% formic acid in acetonitrile (80%). The diluent was prepared by mixing acetonitrile and water at a 90:10 v/v ratio. The retention time for the analyte was determined to be 2.78 min. Accuracy exceeded 99%, and the correlation coefficient was greater than 0.999. The validated HPLC method was characterized as precise, accurate, and robust. Significantly, NMT was found to be susceptible to alkaline, acidic, and peroxide conditions during forced degradation testing. The stability‐indicating method developed effectively separated the degradation products formed during stress testing, underlining its effectiveness in stability testing and offering accuracy, reliability, and sensitivity in determining NMT.

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“…The statistical data were was analyzed for predicted correlation coefficient (predicted R2), adjusted correlation coefficient (adjusted R2), correlation coefficient (R2), and precision. The graphical presentation, 2D contour plots and 3D‐response surface, was created using the response surface methodology (RSM) model (Patil & Deshpande, 2018). The ‘design space’ was applied and implemented for the optimized chromatographic method.…”

Section: Resultsmentioning

confidence: 99%

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

Yenda

Katari

Ettaboina³

et al. 2023

Biomedical Chromatography

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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.

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Development of an Innovative Quality by Design (QbD) Based Stability-Indicating HPLC Method and its Validation for Clofazimine from its Bulk and Pharmaceutical Dosage Forms

Cited by 26 publications

References 14 publications

Interleukin-13-Overexpressing Mice Represent an Advanced Preclinical Model for Detecting the Distribution of Antimycobacterial Drugs within Centrally Necrotizing Granulomas

Interleukin-13-Overexpressing Mice Represent an Advanced Preclinical Model for Detecting the Distribution of Antimycobacterial Drugs within Centrally Necrotizing Granulomas

Development of a novel quality by design–enabled stability‐indicating HPLC method and its validation for the quantification of nirmatrelvir in bulk and pharmaceutical dosage forms

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

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