Development and validation of HPLC method for simultaneous estimation of erlotinib and niclosamide from liposomes
Amruta Prabhakar Padakanti1, Sachin Dattaram Pawar2, Pramod Kumar2
1Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER) Guwahati, Sila village, Changsari, Assam, India.
Abstract:
The emerging drug resistance to the approved first-line drug therapy leads to clinical failure in cancer. Drug repurposing studies lead to the identification of many old drugs to be used for cancer treatment. Combining the repurposed drugs (niclosamide) with first-line therapy agents like erlotinib HCl showed improved efficacy by inhibiting erlotinib HCl acquired resistance. But there is a need to develop a sensitive, accurate, and excellent analytical method and drug delivery system for successfully delivering drug combinations. In the current study, an HPLC method was developed and validated for the simultaneous estimation of niclosamide and erlotinib HCl. The retention time of niclosamide and erlotinib hydrochloride was 6.48 and 7.65 min at 333 nm. The developed method was rapid and sensitive to separating the two drugs with reasonable accuracy, precision, robustness, and ruggedness. A Plackett-Burman (PBD) screening design was used to identify the critical parameters affecting liposomal formulation development using particle size, size distribution, zeta potential, and entrapment efficiency as the response. Lipid concentration, drug concentration, hydration temperature, and media volume were critical parameters affecting the particle size, polydispersity index (PDI), ZP, and %EE of the liposomes. The optimized NCM-ERL liposomes showed the particle size (126.05 ± 2.1), PDI (0.498 ± 0.1), ZP (-16.2 ± 0.3), and %EE of NCM and ERL (50.04 ± 2.8 and 05.42 ± 1.3). In vitro release studies indicated the controlled release of the drugs loaded liposomes (87.06 ± 9.93% and 42.33 ± 0.89% in 24 h).
Insights
This study developed an HPLC method and liposomal drug delivery system for niclosamide and erlotinib HCl combination therapy to overcome cancer drug resistance. The optimized liposomes demonstrated controlled drug release, showing promise for improved cancer treatment efficacy.
Area of Science:
- Pharmaceutical Sciences
- Analytical Chemistry
- Drug Delivery
Background:
- Emerging drug resistance to first-line cancer therapies necessitates novel treatment strategies.
- Drug repurposing, such as using niclosamide, offers potential for combination therapies.
- Erlotinib HCl resistance can be inhibited by combining it with repurposed drugs like niclosamide.
Purpose of the Study:
- To develop and validate a simultaneous HPLC method for estimating niclosamide and erlotinib HCl.
- To create and optimize a liposomal drug delivery system for the niclosamide-erlotinib HCl combination.
- To evaluate the physicochemical properties and in vitro drug release of the optimized liposomal formulation.
Main Methods:
- High-Performance Liquid Chromatography (HPLC) method development and validation for simultaneous drug estimation.
- Plackett-Burman (PBD) screening design for identifying critical parameters in liposomal formulation.
- Characterization of liposomes including particle size, PDI, zeta potential, and entrapment efficiency.
- In vitro drug release studies of niclosamide and erlotinib HCl from liposomes.
Main Results:
- A rapid, sensitive, and validated HPLC method was established for niclosamide and erlotinib HCl.
- Critical parameters for liposomal formulation (lipid concentration, drug concentration, hydration temperature, media volume) were identified.
- Optimized liposomes (NCM-ERL) exhibited favorable characteristics: particle size (126.05 nm), PDI (0.498), ZP (-16.2 mV), and entrapment efficiency (50.04% NCM, 5.42% ERL).
- In vitro studies showed controlled release of both drugs from liposomes over 24 hours.
Conclusions:
- The developed HPLC method is suitable for simultaneous analysis of niclosamide and erlotinib HCl.
- The optimized liposomal formulation provides a promising drug delivery system for cancer combination therapy.
- This approach holds potential for overcoming drug resistance and improving therapeutic outcomes in cancer treatment.
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