Development and characterization of nanostructured lipid carrier-based gels for the transdermal delivery of donepezil

Mendes, I.T.; Ruela, André Luís Morais; Carvalho, Flávia Chiva; Freitas, Jennifer Tavares Jacon; Bonfílio, Rudy; Pereira, Gislaine Ribeiro

doi:10.1016/j.colsurfb.2019.02.007

Cited by 79 publications

(28 citation statements)

References 43 publications

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“…For both optimized NLC formulations, from 4 up to 48 h, the release of rivastigmine was controlled by the diffusion rate of the drug through the lipid matrix or by the lipid matrix degradation in the dissolution medium [ 62 , 102 ]. For the rivastigmine-loaded NLC produced by the ultrasound technique, about 80.75 ± 7.43% of rivastigmine was released after 12 h and the maximum drug release (88.67 ± 3.45%) was observed at 48 h. In contrast, for the rivastigmine-loaded NLC produced by the HPH method, at 12 h the release of rivastigmine was lower (60.13 ± 3.12%) and the maximum drug release (89.25 ± 3.22%) was observed at 48h.…”

Section: Resultsmentioning

confidence: 99%

“…Surfactants should be selected according to their charge, molecular weight, and adequacy for the desired route of administration for the formulation [ 22 , 50 , 60 , 61 ]. Smaller particle sizes have been observed when a higher surfactant/lipid ratio was used [ 31 , 62 , 63 ]. Accordingly, polysorbate 80 (Tween ® 80), a non-ionic surfactant containing a polyoxyethylene chain tetrahydrofuran ring that provides steric stabilization and a hydrophobic tail that prevents particle aggregation, was selected based on previous works that showed its compatibility with the lipids used [ 46 , 52 , 53 , 59 , 60 , 64 ].…”

Section: Methodsmentioning

confidence: 99%

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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

et al. 2020

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

et al. 2020

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“…The emulsion is then vigorously mixed to break the particles down into the micron range. NLCs are then formed by further dispersion of the microemulsion in a chilled hydrophilic phase that causes particles to become smaller [32,41,42]. Although this method can be suitable for the preparation of NLCs loaded with thermolabile drugs, it requires significant amounts of surface active agents and a large volume of water for extensive dilution, which can be considered as the main drawbacks of this technique [24,34,43,44].…”

Section: Microemulsionsmentioning

confidence: 99%

Nanostructured Lipid Carriers for Delivery of Chemotherapeutics: A Review

et al. 2020

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The efficacy of current standard chemotherapy is suboptimal due to the poor solubility and short half-lives of chemotherapeutic agents, as well as their high toxicity and lack of specificity which may result in severe side effects, noncompliance and patient inconvenience. The application of nanotechnology has revolutionized the pharmaceutical industry and attracted increasing attention as a significant means for optimizing the delivery of chemotherapeutic agents and enhancing their efficiency and safety profiles. Nanostructured lipid carriers (NLCs) are lipid-based formulations that have been broadly studied as drug delivery systems. They have a solid matrix at room temperature and are considered superior to many other traditional lipid-based nanocarriers such as nanoemulsions, liposomes and solid lipid nanoparticles (SLNs) due to their enhanced physical stability, improved drug loading capacity, and biocompatibility. This review focuses on the latest advances in the use of NLCs as drug delivery systems and their preparation and characterization techniques with special emphasis on their applications as delivery systems for chemotherapeutic agents and different strategies for their use in tumor targeting.

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“…In particular, transdermal drug delivery has attracted researchers with multiple approaches because multiple dosing or insufficient drug delivery often results in low therapeutic effects [4,5,6,7,8]. Among these techniques, films (patches) and gels have been extensively designed for use in skin diseases or wound care in the past decades [9,10,11,12,13,14,15,16,17]. These dosage forms can also contain drugs for therapeutic applications.…”

Section: Introductionmentioning

confidence: 99%

Controlled Release Film Forming Systems in Drug Delivery: The Potential for Efficient Drug Delivery

Tran

2019

Pharmaceutics

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Despite many available approaches for transdermal drug delivery, patient compliance and drug targeting at the desired concentration are still concerns for effective therapies. Precise and efficient film-forming systems provide great potential for controlling drug delivery through the skin with the combined advantages of films and hydrogels. The associated disadvantages of both systems (films and hydrogels) will be overcome in film-forming systems. Different strategies have been designed to control drug release through the skin, including changes to film-forming polymers, plasticizers, additives or even model drugs in formulations. In the current review, we aim to discuss the recent advances in film-forming systems to provide the principles and review the methods of these systems as applied to controlled drug release. Advances in the design of film-forming systems open a new generation of these systems.

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Development and characterization of nanostructured lipid carrier-based gels for the transdermal delivery of donepezil

Cited by 79 publications

References 43 publications

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

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

Nanostructured Lipid Carriers for Delivery of Chemotherapeutics: A Review

Controlled Release Film Forming Systems in Drug Delivery: The Potential for Efficient Drug Delivery

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