TY - JOUR
T1 - Assessment of pH-shift drug interactions of palbociclib by in vitro micro-dissolution in bio relevant media
T2 - An analytical QbD-driven RP-HPLC method optimization
AU - Patil, Prajakta Harish
AU - Desai, Mrunal
AU - Rao, Rajat Radhakrishna
AU - Mutalik, Srinivas
AU - Shenoy, Gurupur Gautham
AU - Rao, Mahadev
AU - Jagadish, Puralae Channabasavaiah
N1 - Funding Information:
Prajakta Harish Patil would like to express his gratitude for the fellowship and financial support provided by the Indian Council of Medical Research, Government of India. Mrunal Desai wishes to express her gratitude to Manipal College of Pharmaceutical Sciences and Manipal Academy of Higher Education for awarding her the TMA Pai fellowship (IMF) and providing the research facilities.
Funding Information:
This research has been supported by the ICMR India (Ad-hoc research Grant no.2020-4462).
Publisher Copyright:
© 2022. Prajakta Harish Patil et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License
PY - 2022/5
Y1 - 2022/5
N2 - 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 numerical and 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.
AB - 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 numerical and 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.
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U2 - 10.7324/JAPS.2022.120505
DO - 10.7324/JAPS.2022.120505
M3 - Article
AN - SCOPUS:85129925912
SN - 2231-3354
VL - 12
SP - 78
EP - 87
JO - Journal of Applied Pharmaceutical Science
JF - Journal of Applied Pharmaceutical Science
IS - 5
ER -