Assessment of pH-shift drug interactions of palbociclib by in vitro micro-dissolution in bio relevant media: An analytical QbD-driven RP-HPLC method optimization

Patil, Prajakta Harish and Desai, Mrunal and Rao, Rajat Radhakrishna and Mutalik, Srinivas and Shenoy, Gurupur Gautham and Rao, Mahadev and Jagadish, PC (2022) Assessment of pH-shift drug interactions of palbociclib by in vitro micro-dissolution in bio relevant media: An analytical QbD-driven RP-HPLC method optimization. Journal of Applied Pharmaceutical Science, 12 (5). pp. 78-87. ISSN 2231-3354

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Abstract

In the present study, pH-dependent solubility and dissolution of Palbociclib (PB), a weakly basic cyclin-dependent kinase 4/6 inhibitor was investigated by application of analytical quality by design (QbD) approach to an reverse phase high performance liquid chromatography (RP-HPLC) method. An integrated analytical QbD approach for quantification of PB using RP-HPLC was designed by three-level three factorial, Box–Behnken design with numericaland graphical optimization.In vitro micro-dissolution, pH-shift experiments in bio-relevant media were carried out to predict PB’s pH-dependent drug-drug interaction (DDI) behavior. RP-HPLC method developed utilizing a Box–Behnken three-stage three factorial design was shown to be specific towards PB. The optimized method leads to effective and faster chromatographic separation of PB with lower retention time value together with a satisfactory peak symmetry and low peak tailing. Based on in vitro micro-dissolution studies, it was observed that PB has a typical weak base pH-dependent solubility characteristic and dissolution behavior with its release ranging from 98.96% to 102.66% in simulated gastric fluid pH 1.2 before dropping to 43.43% by addition of fasted state simulated intestinal fluid pH 6.5. Overall, our findings demonstrated that in vitro micro-dissolution approaches may accurately predict the intensity of pH-dependent DDI and that the use of these techniques prior to clinical DDIs studies might allow for adequate prediction of pH-dependent drug absorption in vivo

Item Type: Article
Uncontrolled Keywords: Acid-reducing agents; AQbD; CDK inhibitor; Micro-dissolution; pH-dependent drug-drug; Interaction; RP-HPLC
Subjects: Pharmacy > MCOPS Manipal > Pharmaceutical Chemistry
Pharmacy > MCOPS Manipal > Pharmaceutics
Pharmacy > MCOPS Manipal > Pharmacy Practice
Depositing User: KMC Library
Date Deposited: 18 Jul 2022 03:54
Last Modified: 18 Jul 2022 03:54
URI: http://eprints.manipal.edu/id/eprint/158826

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