Eplerenone nanoemulsions for treatment of hypertension. Part I: Experimental design for optimization of formulations and physical characterization

Özdemir, Samet; Çelik, Burak; Acar, Ebru Türköz; Duman, Gülengül; Üner, Melike

doi:10.1016/j.jddst.2018.03.011

Cited by 17 publications

(24 citation statements)

References 46 publications

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“…Particle size and polydispersity index (PI) of nano particulate formulations were measured by the dynamic light scattering (DLS) method by using a Malvern Zetasizer Nano ZS (Malvern Instruments, UK) (22). Before the analysis, formulations were diluted with water (1:20, v:v) and then transferred into disposable polystyrene cuvettes.…”

Section: Characterization Of Formulations Particle Size Analysismentioning

confidence: 99%

Development of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers of Loteprednol Etabonate: Physicochemical Characterization and Ex Vivo Permeation Studies

Uner

Özdemir²,

Taş

et al. 2021

Preprint

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Purpose Loteprednol etabonate (LE) is a new generation corticosteroid that is used for the treatment of inflammatory and allergic conditions of the eye, and management of seasonal allergic rhinitis nasally. LE which is a poorly soluble drug with insufficient bioavailability, has a high binding affinity to steroid receptors. Sophisticated colloidal drug delivery systems of LE could present an alternative for treatment of inflammatory and allergic conditions of the skin. For this purpose, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were attempted to improve for transdermal LE delivery for the first time. Methods SLN and NLC were produced by hot homogenization and ultrasonication technique. Formulations were characterized by dynamic light scattering, scanning electron microscopy, fourier transform infrared spectroscopy and differential scanning calorimetry. Their physical stability was monitored for 3 months of storage. Drug release profiles and permeation properties of SLN and NLC through the porcine skin were investigated. Results It was determined that SLN and NLC below 150 nm particle size had a homogeneous particle size distribution as well as high drug loading capacities. They were found to be stable both physically and chemically at room temperature for 90 days. In terms of release kinetics, it was determined that they released from SLN and NLC in accordance with Fickian diffusion release. Formulations prepared in this study were seen to significantly increase drug penetration through pig skin compared to the control group (p ≤ 0.05). Conclusion SLN and NLC formulations of LE can be stated among the systems that can be an alternative to conventional systems with less side-effect profile in the treatment of inflammatory problems on the skin.

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Section: Characterization Of Formulations Particle Size Analysismentioning

confidence: 99%

Development of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers of Loteprednol Etabonate: Physicochemical Characterization and Ex Vivo Permeation Studies

Uner

Özdemir²,

Taş

et al. 2021

Preprint

Self Cite

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“…In this approach, the factors are manipulated for the desired responses. Then, interactions between the factors and responses can be interpreted using a suitable mathematical model [5]. In this study, we propose a robust optimization approach based on DoE, which may be widely used in many industries and in medicine to achieve the target quality of CKD-497.…”

Section: Research Backgroundmentioning

confidence: 99%

“…Finally, a numerical example shows that the proposed robust desirability function (RDF) can be efficiently applied to pharmaceutical process design. Reference [5], described the successful preparation of nano-emulsions of eplerenone (EP) using non-ionic surfactants. Those formulations were designed and optimized using the design of experiments approach, which accelerates the formulation process and provides desirable properties for the formulations.…”

Section: Literature Reviewmentioning

confidence: 99%

Robust Optimization Approaches for a Natural Pharmaceutical Complex Product of Atractylodes Japonica Koidz and Schisandra Chinensis

et al. 2020

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Experimental results pertaining to natural pharmaceutical complex products (NPCPs) often exhibit large variabilities in their associated response variables. To improve the quality of an NPCP, systemic studies (i.e., statistical analysis and mathematical optimization), including variability analysis and robust optimization, are often required. To this end, a systemic approach for an NPCP development process is proposed by integrating robust design and optimization methodologies. A quality function deployment method can be used to systematically define a standardized manufacturing process and relevant process variables for Chong Kun Dang (CKD)-497. Based on those variables, an experiment is designed using response surface methodology to mathematically estimate the output response functions associated with input variables. In addition, a design space (DS), which can guarantee the quality of an NPCP, is demonstrated by utilizing the overlaid contour plots of the estimated response functions. Finally, a CKD-497 case study is conducted for verification and validation.

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“…Unfortunately, EPL is class II drug according to biopharmaceutical classification system with limited aqueous solubility (less than 1 mg/mL) (Khames, 2019 ), having a maximum aqueous solubility of 0.00908 mg/ml only (Kendre & Chaudhari, 2017 ), in addition to being extensively metabolized into the liver to inactive metabolites (Almeida et al., 2011 ; Salehi et al., 2015 ). This leads to poor oral bioavailability and consequently low therapeutic response (Özdemir et al., 2018b ). Previous studies succeeded to improve its oral bioavailability and biodistribution through the formulation of EPL nano-emulsion and EPL solid dispersion (Almeida et al.…”

Section: Introductionmentioning

confidence: 99%

Lipid-based nano-formulation platform for eplerenone oral delivery as a potential treatment of chronic central serous chorioretinopathy: in-vitro optimization and ex-vivo assessment

2021

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Purpose Eplerenone (EPL) is a selective mineralocorticoid receptor antagonist used for treatment of chronic central serous chorioretinopathy which characterized by accumulation of subretinal fluid causing a localized area of retinal detachment. unfortunately, EPL suffers from poor oral bioavailability due to poor aqueous solubility in addition to high hepatic first pass metabolism. Method Aiming to improve its oral bioavailability, EPL-loaded nanostructured lipid carriers (NLCs) were prepared by the emulsification solvent evaporation method and in-vitro evaluated for particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). A D-optimal design was used for study the effect of liquid lipid to solid lipid ratio, surfactant type and percentage on PS, PDI, EE%, and for data optimization. The optimized EPL-loaded NLCs system was further evaluated using in-vitro drug release and ex-vivo permeation studies through rabbit intestine in comparison to EPL aqueous suspension. The physicochemical properties of the drug in the optimized system were further examined using FT-IR and X-ray diffraction studies. Results The resultant NLCs showed small PS (100.85–346.60 nm), homogenous distribution (0.173–0.624), negatively charged particles (ZP −20.20 to −36.75 mV), in addition to EE% (34.31–70.64%). The optimized EPL-loaded NLCs system with a desirability value of 0.905 was suggested through the Design expert ® software, containing liquid to solid lipid ratio (2:1) in presence of 0.43%w/v Pluronic ® F127 as a surfactant. The optimized EPL-loaded NLCs system showed a PS of 134 nm and PDI of 0.31, in addition to high EE% (76 ± 6.56%w/w), and ZP (-32.37 mV). The ex-vivo permeation study showed two-fold higher drug permeation through rabbit intestine compared to that from the aqueous drug suspension after 24 h, confirming the ability of optimized EPL-loaded NLCs system as successful oral targeting delivery carrier. Conclusion Our results pave the way for a new oral nanotherapeutic approach toward CSCR treatment. In-vivo study is currently under investigation.

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Eplerenone nanoemulsions for treatment of hypertension. Part I: Experimental design for optimization of formulations and physical characterization

Cited by 17 publications

References 46 publications

Development of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers of Loteprednol Etabonate: Physicochemical Characterization and Ex Vivo Permeation Studies

Development of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers of Loteprednol Etabonate: Physicochemical Characterization and Ex Vivo Permeation Studies

Robust Optimization Approaches for a Natural Pharmaceutical Complex Product of Atractylodes Japonica Koidz and Schisandra Chinensis

Lipid-based nano-formulation platform for eplerenone oral delivery as a potential treatment of chronic central serous chorioretinopathy: in-vitro optimization and ex-vivo assessment

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