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Quality by Design Approach for Development and Characterization of Solid Lipid Nanoparticles of Quetiapine Fumarate.

Abstract

BACKGROUND

Quetiapine fumarate, a 2nd generation anti-psychotic drug has oral bioavailability of 9% because of extensive hepatic first pass metabolism. Reports suggest that co-administration of drugs with lipids affects their absorption pathways, enhances lymphatic transport thus bypassing hepatic first pass metabolism resulting in enhanced bioavailability.

OBJECTIVE

The present work was attempted with the aim of developing and characterising potentially lymphatic system absorbable solid lipid nanoparticles (SLN) of Quetiapine fumarate (QF) by Quality by Design approach.

METHOD

Hot emulsification followed by ultrasonication was used as method of preparation. Precirol ATO5, Phospholipon 90G and Poloxamer 188 were used as lipid, stabilizer and surfactant respectively. A 32 Central Composite design (CCD) optimised the 2 independent variables, lipid concentration (X1) and stabilizer concentration (X2) and assessed their effect on percent Entrapment Efficiency (%EE: Y1). The SLN, lyophilized using mannitol, were studied for stability at 5οC ±3 οC and 25 ± 2οC/60 ± 5% RH for 3 months.

RESULTS

The optimised formula derived for SLN had 270mg PrecirolATO5 and 107mg of Phospholipon 90G giving %EE of 76.53%. Mean particle size was 159.8nm with polydispersity index 0.273 and zeta potential -6.6mV. In-vitro drug release followed Korsmeyer-Peppas kinetic model (R2=0.917) with release exponent n=0.722 indicating non-Fickian diffusion . TEM images exhibited particles to be spherical and smooth. FTIR, DSC and XRD studies ascertained drug-excipient compatibility. Stability studies suggested 5οC as appropriate temperature for SLN storage preserving important characteristics within acceptable limits.

CONCLUSION

Development and optimisation by Quality by Design was justified as it yielded SLN having acceptable characteristics and potential application for intestinal lymphatic transport.

Authors+Show Affiliations

Research and Development, Pharmaceutical Sciences, IKGPTU,Kapurthala. India.Department of Pharmaceutics, ASBASJSM College of Pharmacy, Ropar. India.Department of Pharmacy, MSU, Baroda, Vadodara. India.Registrar, CUJ, Ranchi. India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31429691

Citation

Agarwal, Shweta, et al. "Quality By Design Approach for Development and Characterization of Solid Lipid Nanoparticles of Quetiapine Fumarate." Current Computer-aided Drug Design, 2019.
Agarwal S, Garg R, Murthy RSR, et al. Quality by Design Approach for Development and Characterization of Solid Lipid Nanoparticles of Quetiapine Fumarate. Curr Comput Aided Drug Des. 2019.
Agarwal, S., Garg, R., Murthy, R. S. R., & Kumar, S. L. H. (2019). Quality by Design Approach for Development and Characterization of Solid Lipid Nanoparticles of Quetiapine Fumarate. Current Computer-aided Drug Design, doi:10.2174/1573409915666190722122827.
Agarwal S, et al. Quality By Design Approach for Development and Characterization of Solid Lipid Nanoparticles of Quetiapine Fumarate. Curr Comput Aided Drug Des. 2019 Jul 22; PubMed PMID: 31429691.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quality by Design Approach for Development and Characterization of Solid Lipid Nanoparticles of Quetiapine Fumarate. AU - Agarwal,Shweta, AU - Garg,Rajeev, AU - Murthy,R S R, AU - Kumar,S L Hari, Y1 - 2019/07/22/ PY - 2019/01/04/received PY - 2019/06/19/revised PY - 2019/07/04/accepted PY - 2019/8/21/entrez KW - Phospholipon 90G KW - Precirol ATO5 KW - Quality by Design KW - Quetiapine fumarate KW - percent entrapment efficiency KW - solid lipid nanoparticles JF - Current computer-aided drug design JO - Curr Comput Aided Drug Des N2 - BACKGROUND: Quetiapine fumarate, a 2nd generation anti-psychotic drug has oral bioavailability of 9% because of extensive hepatic first pass metabolism. Reports suggest that co-administration of drugs with lipids affects their absorption pathways, enhances lymphatic transport thus bypassing hepatic first pass metabolism resulting in enhanced bioavailability. OBJECTIVE: The present work was attempted with the aim of developing and characterising potentially lymphatic system absorbable solid lipid nanoparticles (SLN) of Quetiapine fumarate (QF) by Quality by Design approach. METHOD: Hot emulsification followed by ultrasonication was used as method of preparation. Precirol ATO5, Phospholipon 90G and Poloxamer 188 were used as lipid, stabilizer and surfactant respectively. A 32 Central Composite design (CCD) optimised the 2 independent variables, lipid concentration (X1) and stabilizer concentration (X2) and assessed their effect on percent Entrapment Efficiency (%EE: Y1). The SLN, lyophilized using mannitol, were studied for stability at 5οC ±3 οC and 25 ± 2οC/60 ± 5% RH for 3 months. RESULTS: The optimised formula derived for SLN had 270mg PrecirolATO5 and 107mg of Phospholipon 90G giving %EE of 76.53%. Mean particle size was 159.8nm with polydispersity index 0.273 and zeta potential -6.6mV. In-vitro drug release followed Korsmeyer-Peppas kinetic model (R2=0.917) with release exponent n=0.722 indicating non-Fickian diffusion . TEM images exhibited particles to be spherical and smooth. FTIR, DSC and XRD studies ascertained drug-excipient compatibility. Stability studies suggested 5οC as appropriate temperature for SLN storage preserving important characteristics within acceptable limits. CONCLUSION: Development and optimisation by Quality by Design was justified as it yielded SLN having acceptable characteristics and potential application for intestinal lymphatic transport. SN - 1875-6697 UR - https://www.unboundmedicine.com/medline/citation/31429691/Quality_by_Design_Approach_for_Development_and_Characterization_of_Solid_Lipid_Nanoparticles_of_Quetiapine_Fumarate L2 - http://www.eurekaselect.com/173695/article DB - PRIME DP - Unbound Medicine ER -