Quality by design (QbD)–based fabrication of atazanavir-loaded nanostructured lipid carriers for lymph targeting: bioavailability enhancement using chylomicron flow block model and toxicity studies

2021 ◽  
Author(s):  
Vishal C. Gurumukhi ◽  
Sanjaykumar B. Bari
Keyword(s):  
Quality By Design ◽  
Nanostructured Lipid Carriers ◽  
Block Model ◽  
Bioavailability Enhancement ◽  
Toxicity Studies

scholarly journals Quality by design (QbD) based fabrication of atazanavir loaded nanostructured lipid carriers for lymph targeting: Bioavailability enhancement using chylomicron flow block model and toxicity study

2021 ◽  
Author(s):  
Vishal Gurumukhi ◽  
Sanjaykumar Bari
Keyword(s):  
High Pressure ◽  
Quality By Design ◽  
Aqueous Solubility ◽  
Relative Bioavailability ◽  
Nanostructured Lipid Carriers ◽  
Block Model ◽  
Critical Material ◽  
Bioavailability Enhancement

Abstract Atazanavir (ATV) is widely used as anti-HIV agent with poor aqueous solubility which requires fabrication of novel drug delivery system to enhance therapeutic activity and safety. For this purpose, the quality by design (QbD) based ATV loaded nanostructured lipid carriers (NLCs) to address the challenges of bioavailability and its safety on oral administration. Herein, the main objective was to identify the influencing variables for the production of quality product. Considering this objective, quality target product profile (QTPP) was assigned and a systematic risk assessment study was performed to identify the critical material attributes (CMAs) and critical process parameter (CPP) having an influence on critical quality attributes (CQAs). Lipid concentrations, surfactant concentrations, and pressure of high-pressure homogenizer were identified as CMAs and CPP. ATV-NLCs were prepared by emulsification-high pressure homogenization method and further lyophilized to obtain solid-state NLCs. The effect of formulation variables (CMAs and CPP) on responses like particle size (Y1), polydispersity index (Y2), and zeta potential (Y3) was observed by central composite rotatable design (CCRD). The data were statistically evaluated by ANOVA for confirmation of a significant level (P<0.05). The optimal conditions of NLCs were obtained by generating design space and desirability value. The lyophilized ATV-NLCs were characterized by DSC, PXRD, and FT-IR analysis. The morphology of NLCs was revealed by TEM and FESEM. In vitro study suggested a sustained release pattern of drug (92.37±1.03 %) with a mechanism of Korsmeyer-Peppas model (r2 =0.925, and n=0.63). In vivo evaluation in Wistar rats showed significantly higher (p<0.001) plasma drug concentration of ATV-NLCs as compared to ATV-suspension using chylomicron flow block model. The relative bioavailability of ATV-NLCs was obtained to be 2.54 folds. Thus, a safe and promising drug targeting system was successfully developed to improve bioavailability and avoiding first-pass effect ensures to circumvent the acute-toxicity of liver.

scholarly journals Application of the quality-by-design (QbD) approach to improve the nose-to-brain delivery of diazepam-loaded nanostructured lipid carriers (NLC)

2020 ◽  
Author(s):  
Cláudia Costa ◽  
Sara Cunha ◽  
Andreia Peixoto ◽  
João Moreira ◽  
José Sousa Lobo ◽  
...  
Keyword(s):  
Quality By Design ◽  
Nanostructured Lipid Carriers ◽  
Brain Delivery

scholarly journals Nanostructured lipid carriers employing polyphenols as promising anticancer agents: Quality by design (QbD) approach

2017 ◽  
Vol 526 (1-2) ◽  
pp. 506-515 ◽  
Author(s):  
Ketki Bhise ◽  
Sushil Kumar Kashaw ◽  
Samaresh Sau ◽  
Arun K. Iyer
Keyword(s):  
Anticancer Agents ◽  
Quality By Design ◽  
Nanostructured Lipid Carriers

scholarly journals Double Optimization of Rivastigmine-Loaded Nanostructured Lipid Carriers (NLC) for Nose-to-Brain Delivery Using the Quality by Design (QbD) Approach: Formulation Variables and Instrumental Parameters

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 599 ◽  
Author(s):  
Sara Cunha ◽  
Cláudia Pina Costa ◽  
Joana A. Loureiro ◽  
Jorge Alves ◽  
Andreia F. Peixoto ◽  
...  
Keyword(s):  
Particle Size ◽  
High Pressure ◽  
Drug Release ◽  
Quality By Design ◽  
Nanostructured Lipid Carriers ◽  
Brain Delivery ◽  
High Pressure Homogenization ◽  
Ultrasound Technique ◽  
Formulation Variables

Rivastigmine is a drug commonly used in the management of Alzheimer’s disease that shows bioavailability problems. To overcome this, the use of nanosystems, such as nanostructured lipid carriers (NLC), administered through alternative routes seems promising. In this work, we performed a double optimization of a rivastigmine-loaded NLC formulation for direct drug delivery from the nose to the brain using the quality by design (QbD) approach, whereby the quality target product profile (QTPP) was the requisite for nose to brain delivery. The experiments started with the optimization of the formulation variables (or critical material attributes—CMAs) using a central composite design. The rivastigmine-loaded NLC formulations with the best critical quality attributes (CQAs) of particle size, polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) were selected for the second optimization, which was related to the production methods (ultrasound technique and high-pressure homogenization). The most suitable instrumental parameters for the production of NLC were analyzed through a Box–Behnken design, with the same CQAs being evaluated for the first optimization. For the second part of the optimization studies, were selected two rivastigmine-loaded NLC formulations: one produced by ultrasound technique and the other by the high-pressure homogenization (HPH) method. Afterwards, the pH and osmolarity of these formulations were adjusted to the physiological nasal mucosa values and in vitro drug release studies were performed. The results of the first part of the optimization showed that the most adequate ratios of lipids and surfactants were 7.49:1.94 and 4.5:0.5 (%, w/w), respectively. From the second part of the optimization, the results for the particle size, PDI, ZP, and EE of the rivastigmine-loaded NLC formulations produced by ultrasound technique and HPH method were, respectively, 114.0 ± 1.9 nm and 109.0 ± 0.9 nm; 0.221 ± 0.003 and 0.196 ± 0.007; −30.6 ± 0.3 mV and −30.5 ± 0.3 mV; 97.0 ± 0.5% and 97.2 ± 0.3%. Herein, the HPH was selected as the most suitable production method, although the ultrasound technique has also shown effectiveness. In addition, no significant changes in CQAs were observed after 90 days of storage of the formulations at different temperatures. In vitro studies showed that the release of rivastigmine followed a non-Fickian mechanism, with an initial fast drug release followed by a prolonged release over 48 h. This study has optimized a rivastigmine-loaded NLC formulation produced by the HPH method for nose-to-brain delivery of rivastigmine. The next step is for in vitro and in vivo experiments to demonstrate preclinical efficacy and safety. QbD was demonstrated to be a useful approach for the optimization of NLC formulations for which specific physicochemical requisites can be identified.

Tacrolimus-loaded nanostructured lipid carriers for oral delivery-in vivo bioavailability enhancement

2016 ◽  
Vol 109 ◽  
pp. 149-157 ◽  
Author(s):  
Saba Khan ◽  
M. Shaharyar ◽  
Mohammad Fazil ◽  
Md Quamrul Hassan ◽  
Sanjula Baboota ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Nanostructured Lipid Carriers ◽  
Bioavailability Enhancement

scholarly journals Preparation and Characterization of Fenofibrate-Loaded Nanostructured Lipid Carriers for Oral Bioavailability Enhancement

2014 ◽  
Vol 15 (6) ◽  
pp. 1509-1515 ◽  
Author(s):  
Tuan Hiep Tran ◽  
Thiruganesh Ramasamy ◽  
Duy Hieu Truong ◽  
Han-Gon Choi ◽  
Chul Soon Yong ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Nanostructured Lipid Carriers ◽  
Bioavailability Enhancement

Development and optimization of Luliconazole Nanostructured lipid carriers based gel by Quality by Design its skin distribution studies, dermatokinetic modeling & In-vitro and Ex-vivo correlation

2020 ◽  
Vol 18 ◽  
Author(s):  
Eranti Bhargav ◽  
Yiragamreddy Padmanabha Reddy ◽  
Koteshwara Kunnatur B
Keyword(s):  
Particle Size ◽  
Quality By Design ◽  
Fungal Infections ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Nanostructured Lipid Carriers ◽  
Fractional Factorial ◽  
Sonication Time ◽  
Drug Concentrations

Objective : The present study was aimed to improve the permeability of Luliconazole (LZ) and to localize high drug concentrations at skin layers by Quality by Design (QbD) based Nanostructured lipid carriers (NC) based gel. Methods: Quality Target Product Profile was set and Critical Quality attributes were identified. FT-IR and DSC studies confirmed compatibility. Risk assessment was carried out by screening the factors using 27-27-2 fractional factorial design and optimization by Box Behnken design. Cholesterol: Cetyl Palmitate, PEG 200 and probe sonication time were identified as factors, Particle size (<200 nm), PDI (0.4), % Entrapment efficiency (% EE, >80%) and % Cumulative Drug release (% CDR, >95%) as responses. Contour plots, Overlay plots and desirability were utilized to create design space. Results: The quadratic polynomial equations showed that increased lipid content, PEG 200 and optimum sonication time reduced Particle size, PDI, improved % EE and % CDR. The optimized formula was formulated into a gel. Ex-vivo permeation studies performed using pig ear pinna skin revealed that developed LZ NC gel exhibited greater permeation 272.98±8.57 (µg/cm2 ) and 32.11 ±4.7 (µg/cm2 /h) flux than plain drug dispersed gel. Dermatokinetic parameters of LZ NC gel revealed that highly significant amount of LZ was permeated, distributed and transported through the skin layers. The better linear correlations were obtained by LZ permeation through synthetic membrane (in-vitro) and pig ear pinna skin (ex-vivo). Conclusion: The above findings revealed that developed LZ NC gel exhibited better permeation and localization at skin layers in treating fungal infections.

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