4 research outputs found
Synthesis and Optimization of Canagliflozin by Employing Quality by Design (QbD) Principles
Efforts toward a synthesis and process
optimization of canagliflozin <b>1</b> are described. Canagliflozin
synthesis was accomplished
via purified open ring intermediate <b>12</b>. The process was
optimized by employing quality by design (QbD) methodologies, and
a telescopic strategy was executed for the first three and last two
steps in a total six-step sequence. Optimization of the Friedel–Craft
acylation reaction followed by Lewis acid mediated reductive elimination, <i>n</i>-BuLi mediated <i>C</i>-arylation, and reductive
demethoxylation was performed to develop a robust process. These steps
were found to be critical; therefore, critical process parameters
(CPPs) were identified by employing design of experiment (DoE) methodology.
In addition, control strategies for dealing with impurities are described
Synthesis and Optimization of Canagliflozin by Employing Quality by Design (QbD) Principles
Efforts toward a synthesis and process
optimization of canagliflozin <b>1</b> are described. Canagliflozin
synthesis was accomplished
via purified open ring intermediate <b>12</b>. The process was
optimized by employing quality by design (QbD) methodologies, and
a telescopic strategy was executed for the first three and last two
steps in a total six-step sequence. Optimization of the Friedel–Craft
acylation reaction followed by Lewis acid mediated reductive elimination, <i>n</i>-BuLi mediated <i>C</i>-arylation, and reductive
demethoxylation was performed to develop a robust process. These steps
were found to be critical; therefore, critical process parameters
(CPPs) were identified by employing design of experiment (DoE) methodology.
In addition, control strategies for dealing with impurities are described
Identification, Synthesis, and Strategy For Minimization of Potential Impurities Observed In Raltegravir Potassium Drug Substance
Multiple sources of anticipated degradation and process
impurities
of raltegravir potassium drug substance observed during the laboratory
optimization and later during its bulk synthesis are described in
this article. The impurities were monitored by UPLC, and their structures
are tentatively assigned on the basis of fragmentation patterns in
LC–MS and NMR spectroscopy. Most of the impurities are synthesized,
and their assigned constitutions were confirmed by co-injection in
UPLC. In addition to the formation, synthesis, and characterization,
strategy for minimizing these impurities to the level accepted by
ICH is also described. We feel that our study will be helpful to the
generic industry for obtaining chemically pure raltegravir potassium
Identification, Synthesis, and Strategy For Minimization of Potential Impurities Observed In Raltegravir Potassium Drug Substance
Multiple sources of anticipated degradation and process
impurities
of raltegravir potassium drug substance observed during the laboratory
optimization and later during its bulk synthesis are described in
this article. The impurities were monitored by UPLC, and their structures
are tentatively assigned on the basis of fragmentation patterns in
LC–MS and NMR spectroscopy. Most of the impurities are synthesized,
and their assigned constitutions were confirmed by co-injection in
UPLC. In addition to the formation, synthesis, and characterization,
strategy for minimizing these impurities to the level accepted by
ICH is also described. We feel that our study will be helpful to the
generic industry for obtaining chemically pure raltegravir potassium