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
By: Kolasani, Durga Deepthi
.
Contributor(s): Desai, Mrunal.
Publisher: Bangalore Association of Pharmaceutical Teachers of India (APTI) 2022Edition: Vol.56(4), Oct-Dec.Description: 1219-1225p.Subject(s): PHARMACEUTICSOnline resources: Click here
In:
Indian journal of pharmaceutical education and researchSummary: 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.
| Item type | Current location | Call number | Status | Date due | Barcode | Item holds |
|---|---|---|---|---|---|---|
Articles Abstract Database
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School of Pharmacy Archieval Section | Not for loan | 2023-0129 |
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.
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