Forced degradation of flibanserin bulk drug: Development and validation of stability indicating RP-HPLC method
By: Chew, Yik-Ling
.
Contributor(s): Lee, Hon-Kent.
Publisher: Karnataka Association of Pharmaceutical Teachers of India (APTI) 2022Edition: Vol.56(1), Jan-Mar.Description: 32-42p.Subject(s): PHARMACEUTICSOnline resources: Click here
In:
Indian journal of pharmaceutical education and researchSummary: Background: Flibanserin had been approved as the first drug by United State Food and
Drug Administration (USFDA) for the treatment of female sexual interest/arousal disorder
of any severity. However, the stability of this drug has yet to be studied extensively.
Objectives: The objectives of this study were to optimize the stability indicating method
and evaluate the stability of flibanserin under various forced degradation conditions,
determine the order of the degradation kinetics, half-life and shelf life of flibanserin under
certain stress conditions. The stability of flibanserin under various stress conditions which
would reflect the important aspects of storage condition and excipients which should be
avoided in the formulation of this drug substance into final drug products. Methods:
Stability indicating method was developed using HPLC. It was validated according to
ICH guideline for its linearity, precision, accuracy, robustness, LOD and LOQ. The forced
degradation was performed under various stress conditions, namely acidic, alkaline and
oxidative conditions (H2O2, AIBN and FeCl3). LC-MS was utilised for identification of the
degradation impurities, and the degradation kinetics was evaluated based on the kinetic
models. Results: Degradation of flibanserin was noticed under oxidative conditions.
Flibanserin was degraded under H2O2 oxidation at room temperature, while AIBN and
FeCl3 at elevated temperature. Two N-oxide impurities were identified under H2O2
oxidation. Flibanserin was degraded following the first-order kinetic under H2O2 and AIBN
oxidation, while zero-order under FeCl3 oxidation. Half-life and shelf life of flibanserin
under respective stress conditions were determined. Conclusion: It is concluded that
the RP-HPLC method developed could be used as the stability indicating method in
determination of flibanserin stability and its impurities. Flibanserin is sensitive towards
oxidative degradation. The impurities and the order of the degradation kinetics were identified.
| Item type | Current location | Call number | Status | Date due | Barcode | Item holds |
|---|---|---|---|---|---|---|
Articles Abstract Database
|
School of Pharmacy Archieval Section | Not for loan | 2022-1695 |
Background: Flibanserin had been approved as the first drug by United State Food and
Drug Administration (USFDA) for the treatment of female sexual interest/arousal disorder
of any severity. However, the stability of this drug has yet to be studied extensively.
Objectives: The objectives of this study were to optimize the stability indicating method
and evaluate the stability of flibanserin under various forced degradation conditions,
determine the order of the degradation kinetics, half-life and shelf life of flibanserin under
certain stress conditions. The stability of flibanserin under various stress conditions which
would reflect the important aspects of storage condition and excipients which should be
avoided in the formulation of this drug substance into final drug products. Methods:
Stability indicating method was developed using HPLC. It was validated according to
ICH guideline for its linearity, precision, accuracy, robustness, LOD and LOQ. The forced
degradation was performed under various stress conditions, namely acidic, alkaline and
oxidative conditions (H2O2, AIBN and FeCl3). LC-MS was utilised for identification of the
degradation impurities, and the degradation kinetics was evaluated based on the kinetic
models. Results: Degradation of flibanserin was noticed under oxidative conditions.
Flibanserin was degraded under H2O2 oxidation at room temperature, while AIBN and
FeCl3 at elevated temperature. Two N-oxide impurities were identified under H2O2
oxidation. Flibanserin was degraded following the first-order kinetic under H2O2 and AIBN
oxidation, while zero-order under FeCl3 oxidation. Half-life and shelf life of flibanserin
under respective stress conditions were determined. Conclusion: It is concluded that
the RP-HPLC method developed could be used as the stability indicating method in
determination of flibanserin stability and its impurities. Flibanserin is sensitive towards
oxidative degradation. The impurities and the order of the degradation kinetics were identified.
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