{"title":"Voriconazole Loaded Lipidic Nanoparticles for Ophthalmic Delivery: Development Using QbD Combined with Risk-based Approach","authors":"Akanksha Patel, A. Dharamsi","doi":"10.2174/2468187313666230420075952","DOIUrl":null,"url":null,"abstract":"\n\nVoriconazole (VRZ) is widely used for fungal keratitis topically. It is sparingly water soluble and has limited permeability which can lead to poor bioavailability. Nanostructured Lipid Carriers (NLCs) are selected as a carrier for voriconazole as they increase solubility\nwhile the lipidic character of the formulation facilitates permeation.\n\n\n\no To develop a new method of preparation of lipidic nanoparticles\no To apply Quality by design and risk-based approach to find variables\no To optimize variables and find the design space\no To evaluate and characterize the optimized formulation\n\n\n\nThe present study is an attempt to address the challenges in the formulation of NLCs using a high-speed homogenizer. Quality by Design approach was used to find the material attributes\nand process parameters playing a significant role in the formulation development. Quality Target\nproduct profile was prepared, and failure mode and effect analysis was performed for a better understanding of the risks, ways to alleviate risks, and finally, to propose a control strategy. The formulation was optimized by using 3-levels 3-factors central composite design, and design space was\nobtained by using graphical optimization. The morphology of the particles was studied by using\nTransmission Electron Microscope. In vitro drug release study was performed using Franz diffusion\ncell.\n\n\n\nThe amount of solid lipid, solid lipid to total lipid ratio, and concentration of surfactant\nwere found to be high risk variables and their effects on the product quality were examined using\nCentral composite design considering particle size, particle size distribution and %entrapment\nefficiency as dependent variables. Optimized NLC had a particle size of 72.58 nm with PDI 0.137\nand %entrapment efficiency of 78.79%. The in vitro drug release study showed sustained drug\nrelease over the period of 24 hrs and followed the Higuchi model with a fickian diffusion mechanism\n\n\n\nThe present study successfully explored QbD along with Risk-based approach for the\ndevelopment of voriconazole containing lipidic nanoparticles.\n","PeriodicalId":10818,"journal":{"name":"Current Nanomedicine","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2023-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Nanomedicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/2468187313666230420075952","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Voriconazole (VRZ) is widely used for fungal keratitis topically. It is sparingly water soluble and has limited permeability which can lead to poor bioavailability. Nanostructured Lipid Carriers (NLCs) are selected as a carrier for voriconazole as they increase solubility
while the lipidic character of the formulation facilitates permeation.
o To develop a new method of preparation of lipidic nanoparticles
o To apply Quality by design and risk-based approach to find variables
o To optimize variables and find the design space
o To evaluate and characterize the optimized formulation
The present study is an attempt to address the challenges in the formulation of NLCs using a high-speed homogenizer. Quality by Design approach was used to find the material attributes
and process parameters playing a significant role in the formulation development. Quality Target
product profile was prepared, and failure mode and effect analysis was performed for a better understanding of the risks, ways to alleviate risks, and finally, to propose a control strategy. The formulation was optimized by using 3-levels 3-factors central composite design, and design space was
obtained by using graphical optimization. The morphology of the particles was studied by using
Transmission Electron Microscope. In vitro drug release study was performed using Franz diffusion
cell.
The amount of solid lipid, solid lipid to total lipid ratio, and concentration of surfactant
were found to be high risk variables and their effects on the product quality were examined using
Central composite design considering particle size, particle size distribution and %entrapment
efficiency as dependent variables. Optimized NLC had a particle size of 72.58 nm with PDI 0.137
and %entrapment efficiency of 78.79%. The in vitro drug release study showed sustained drug
release over the period of 24 hrs and followed the Higuchi model with a fickian diffusion mechanism
The present study successfully explored QbD along with Risk-based approach for the
development of voriconazole containing lipidic nanoparticles.