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The management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the various strategies that have been studied to circumvent this challenge, the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results. In addition, the encapsulation of the drugs in lipid-based nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) or nanoemulsions (NEs), can improve nose-to-brain transport by increasing the bioavailability and site-specific delivery. This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers (SLNs, NLCs and NEs) for nose-to-brain delivery. Based on the literature available from the past two years, we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration. The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out. Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear, it appears that the intranasal route together with the use of NLCs, SLNs or NEs is advantageous for targeting drugs to the brain. These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs, so they are expected to be approved by regulatory authorities in the coming years. Intranasal delivery of nanostructured lipid carriers (NLC), solid lipid nanoparticles (SLN) and nanoemulsions in rats and rabbits resulted in higher drug concentration in the brain, compared to blood, proving the effectiveness of nose-to-brain delivery. [Display omitted] [ABSTRACT FROM AUTHOR]

Quality-by-design (QbD) approach has been applied to optimize lipid-based nanosystems formulations, including solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions, besides being increasingly requested by regulatory authorities. Different mathematical models and statistical tests have been used, with similar conclusions regarding the parameters that influence the physical features of the resulting nanosystems. These include, variations in composition (e.g. lipid(s) and/or emulsifier(s)) and manufacturing parameters (e.g. emulsification rate and/or time, sonication amplitude and/or time, and homogenization pressure and/or cycles). These are critical parameters that influence nanoparticle/globule mean size, polydispersity index, zeta potential, drug encapsulation efficiency and in vitro drug release. This review addresses the concepts and applications of QbD for the development of lipid-based nanosystems, reporting successful examples published in the last 2 years. Although, some limitations have been identified, it is expected that in the upcoming years the application of QbD in pharmaceutical development will be an established approach. Unlabelled Image [ABSTRACT FROM AUTHOR]

• HPβCD was used for the first time to prepare 3D printed formulations (printlets). • Micro-extrusion printing enabled in situ formation of HPβCD-carbamazepine complexes. • Orodispersible and immediate release printlets were successfully prepared. • Small changes in cellulose ethers ratio allowed fine tuning of drug release profile. This work aimed to explore for the first time the use of cyclodextrins to prepare printlets of poorly soluble drugs, such as carbamazepine, which require fine dose adjustment and rapid release. Orodispersible (flash) and immediate release formulations were 3D printed via semisolid extrusion of wet masses of hydroxypropyl-β-cyclodextrin (HPβCD) and cellulose ethers and regulating tablet porosity. Rheology of the wet masses allowed identifying printable compositions. Printing robustness was assessed evaluating weight, dimensions, hardness, drug content, and microstructure. Drug crystallinity, printlet disintegration and dissolution profiles were also characterized. The results highlight the feasibility of using HPβCD as excipient in printlets of poorly soluble drugs, and the possibilities of tuning drug release profiles through small changes in cellulose ethers nature and ratio. Semisolid extrusion-based 3D printing is revealed as a feasible approach to in situ form carbamazepine-HPβCD complexes and to produce printlets with suitable physical and drug release properties for oral delivery. [ABSTRACT FROM AUTHOR]

Adherence to topical treatment has been less studied in comparison with systemic therapeutic regimens and is poorly understood. High-quality research on this area is essential to outline a strategy to increase medication adherence and clinical outcomes. For a more comprehensive understanding of this issue, a systematic review of the methodologies for topical treatment adherence evaluation in psoriasis was undertaken. Twenty one studies were selected from the literature which used six different adherence methodologies. Merely three studies used multiple adherence measurement methods. The most used method was questionnaire (44%) which was also associated with higher variability of the adherence results. One possible explanation is the lack of a validated questionnaire designed specifically for the evaluation of adherence to topical treatment. Only one method (medication weight) takes into consideration the applied dose. However, the estimation of the expected weight is complex, which renders this method, as used presently, less effective. The use of a dosing device could improve its accuracy and be helpful to clearly instruct the patients about the correct dose. As there is no single method that allows an accurate and complete assessment of adherence it is recommended to use a combination of methods, including self-report and medicines’ weight measurements. [ABSTRACT FROM AUTHOR]