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Published on:September 2022
Indian Journal of Pharmaceutical Education and Research, 2022; 56(4):1219-1225
Original Article | doi:10.5530/ijper.56.4.203

Evaluation of pH Dependent Solubility and Examination of Variation in Pharmacokinetic Properties of Alectinib: A Quantitative Study by Implementing Integrated Quality by Design Approach for RP-HPLC Method Development and Optimization

Authors and affiliation (s):

Durga Deepthi Kolasani, Mrunal Desai, Prajakta Patil, Jagadish Puralae Channabasavaiah*

Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, INDIA.


Introduction: Alectinib, an anaplastic lymphoma kinase inhibitor of BCS class IV, is said to have pH-dependent solubility and is susceptible to interactions with co-prescribed acid-reducing agents. Objectives: A micro-dissolution study was performed to determine the effect of modulations in gastrointestinal pH using biorelevant media and a sensitive RP-HPLC technique was developed for quantification of alectinib in the same using quality by design approach. Materials and Methods: Analytical method was developed and optimized in accordance with box-behnken design followed by micro-dissolution experiment mimicking physiological pH shift. Results: The solubility of alectinib in FaSSGF decreased from 0.648 μg/ml to 0.270 μg/ml whereas in FaSSIF it dropped down from 0.574 μg/ml to 0.108 μg/ml at the end of the micro-dissolution experiment. This reveals that elevation of pH from 1.2 to 6.8 has no significant impact on its solubility and hence will not influence drug absorption. Conclusion: Nonetheless, the study would be useful for therapeutic medication monitoring, dose adjustment of co-administered drugs, proactively driving clinical research design, and obtaining a readout on pH liability for high-risk anticancer medications.

Keywords: Alectinib, QbD, pH, ALK kinase, Micro dissolution.



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The Official Journal of Association of Pharmaceutical Teachers of India (APTI)
(Registered under Registration of Societies Act XXI of 1860 No. 122 of 1966-1967, Lucknow)

Indian Journal of Pharmaceutical Education and Research (IJPER) [ISSN-0019-5464] is the official journal of Association of Pharmaceutical Teachers of India (APTI) and is being published since 1967.


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