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Spray congealed lipid microparticles for the local delivery of β-galactosidase to the small intestine
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Effect of polyoxylglycerides-based excipients (Gelucire®) on ketoprofen amorphous solubility and crystallization from the supersaturated state
No full textPolyoxylglycerides-based solid mixtures, commercially known as Gelucire®, are excipients commonly used for bioavailability improvement of poorly water-soluble drugs. However, their effect on solutions containing hydrophobic drugs above crystalline solubility has not yet been explored. The goal of this study was to investigate the impact of a mix of two commercial Gelucire® with high HLB values (Gelucire®50/13 and Gelucire®48/16) on the amorphous solubility and crystallization from supersaturated solutions of ketoprofen, used as model drug. The results evidenced a strong interaction between Gelucire® components and the drug-rich nanodroplets generated upon liquid–liquid phase separation. This led to two important consequences: on one hand, the drug amorphous solubility was decreased, together with the amorphous-to-crystalline solubility ratio; on the other hand, the enlargement and coalescence of the drug-rich droplets were prevented. This stabilizing effect towards the drug-rich phase was comparable to, or even stronger than, that obtained with traditional amorphous polymers (PVP or HPMC) and contributed to inhibiting drug crystallization. Notably, the impact of Gelucire® on drug crystallization from the supersaturated state depended on its micellar behaviour: the monomeric form (below 50 μg/mL) accelerated the formation of crystals, whereas pre-micellar aggregates (50–500 μg/mL) and solubilizing micelles (above 500 μg/mL) inhibited drug crystallization. These findings will contribute to a better understanding of the behaviour of supersaturated drug solutions in the presence of Gelucire® and will facilitate the rational design of supersaturating drug delivery systems containing these excipients
Manual dexterity predicts phonological decoding speed in typical reading adults
No full textManual dexterity and phonological decoding involve the posterior parietal cortex, which controls location coding for visually guided actions, as well as a large fronto-cerebellar network. We studied the relationship between manual dexterity and reading ability in adult typical readers. Two measurements of manual dexterity were collected to index the procedural learning effect. A linear regression model demonstrated that phonological short-term memory, manual dexterity at time 1 and procedural learning of manual dexterity predicted phonological decoding speed. Similar results were found when left-hand dexterity at time 1 and procedural learning dexterity were entered last. The better one’s phonological decoding skill was, the less fluent their manual dexterity was, suggesting a recycle from object–location to letter–location coding. However, the greater the procedural learning, the faster phonological decoding was, suggesting that larger plasticity of object–location coding was linked to better letter–location coding. An independent role of the interhemispheric connections or of the right posterior parietal cortex is also suggested
Spray congealing: An emerging technology to prepare solid dispersions with enhanced oral bioavailability of poorly water soluble drugs
Full text linkThe low and variable oral bioavailability of poorly water soluble drugs remains a major concern for the pharmaceutical industry. Spray congealing is an emerging technology for the production of solid dispersion to enhance the bioavailability of poorly soluble drugs by using low-melting hydrophilic excipients. The main advantages are the absence of solvents and the possibility to obtain spherical free-flowing microparticles (MPs) by a relatively inexpensive, simple, and one-step process. This review aims to fully describe the composition, structure, physico-chemical properties, and characterization techniques of spray congealed-formulations. Moreover, the influence of these properties on the MPs performance in terms of solubility and dissolution enhancement are examined. Following, an overview of the different spray congealed systems developed to increase the oral drug bioavailability is provided, with a focus on the mechanisms underpinning the bioavailability enhancement. Finally, this work gives specific insights on the main factors to be considered for the rational formulation, manufacturing, and characterization of spray congealed solid dispersions
Liquid lipids act as polymorphic modifiers of tristearin-based formulations produced by melting technologies
Full text linkDespite the growing interest in lipid-based formulations, their polymorphism is still a challenge in the pharmaceutical industry. Understanding and controlling the polymorphic behavior of lipids is a key element for achieving the quality and preventing stability issues. This study aims to evaluate the impact of different oral-approved liquid lipids (LL) on the polymorphism, phase transitions and structure of solid lipid-based formulations and explore their influence on drug release. The LL investigated were isopropyl myristate, ethyl oleate, oleic acid, medium chain trigycerides, vitamin E acetate, glyceryl monooleate, lecithin and sorbitane monooleate. Spraycongealing was selected as an example of a melting-based solvent-free manufacturing method to produce microparticles (MPs) of tristearin (Dynasan®118). During the production process, tristearin MPs crystallized in the metastable α-form. Stability studied evidenced a slow phase transition to the stable β-polymorph overtime, with the presence of the α-form still detected after 60 days of storage at 25◦C. The addition of 10% w/w of LL promoted the transition of tristearin from the α-form to the stable β-form with a kinetic varying from few minutes to days, depending on the specific LL. The combination of various techniques (DSC, X-ray diffraction analysis, Hot-stage polarized light microscopy, SEM) showed that the addition of LL significantly modified the crystal structure of tristearin-based formulations at different length scales. Both the polymorphic form and the LL addition had a strong influence on the release behavior of a model hydrophilic drug (caffeine). Overall, the addition of LL can be considered an interesting approach to control triglyceride crystallization in the β-form. From the industrial viewpoint, this approach might be advantageous as any polymorphic change will be complete before storage, hence enabling the production of stable lipid formulations
Different BCS class II drug-gelucire solid dispersions prepared by spray congealing: Evaluation of solid state properties and in vitro performances
Full text linkDelivery of poorly water soluble active pharmaceutical ingredients (APIs) by semi-crystalline solid dispersions prepared by spray congealing in form of microparticles (MPs) is an emerging method to increase their oral bioavailability. In this study, solid dispersions based on hydrophilic Gelucires® (Gelucire® 50/13 and Gelucire® 48/16 in different ratio) of three BCS class II model compounds (carbamazepine, CBZ, tolbutamide, TBM, and cinnarizine, CIN) having different physicochemical properties (logP, pKa, Tm) were produced by spray congealing process. The obtained MPs were investigated in terms of morphology, particles size, drug content, solid state properties, drug-carrier interactions, solubility, and dissolution performances. The solid-state characterization showed that the properties of the incorporated drug had a profound influence on the structure of the obtained solid dispersion: CBZ recrystallized in a different polymorphic form, TBM crystallinity was significantly reduced as a result of specific interactions with the carrier, while smaller crystals were observed in case of CIN. The in vitro tests suggested that the drug solubility was mainly influenced by carrier composition, while the drug dissolution behavior was affected by the API solid state in the MPs after the spray congealing process. Among the tested APIs, TBM- Gelucire dispersions showed the highest enhancement in drug dissolution as a result of the reduced drug crystallinity
Nanomaterials for oral drug administration
No full textIn the last decade, a wide variety of oral nano-scaled drug delivery systems have been developed. This book chapter first gives a background on the challenges associated with the design of oral drug formulations, in relation to the well-known barriers presented by the gastrointestinal tract. Then, the most common nanomaterials used for oral formulations, which are classified as nanocrystals and nanosuspensions, polymeric, lipid and inorganic-based nanocarriers are described, plus a view on the most advanced nanomaterials, such as hybrid, protein and stimuli-responsive nanocarriers. Specifically, the properties, advantages and disadvantages of the different nanomaterials are reported. The design aspects of nanosystems for the targeting of specific gastrointestinal regions are also highlighted. Finally, critical considerations on the approaches to convert nanocarriers into final dosage forms suitable for oral administration, which are crucial to make these nanocarriers clinically and commercially available, are provided
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