1,721,061 research outputs found
Spray congealed lipid microparticles for the local delivery of β-galactosidase to the small intestine
No full textDevelopment of microparticles for oral administration of the non-conventional radical scavenger IAC and testing in an inflammatory rat model.
No full textDevelopment of microparticles for oral administration of the non-conventional radical scavenger
IAC and testing in an inflammatory rat model
1)Cirillo S.. 2)Paolini M.. 3)Vivarelli F.. 4)Passerini N.. 5)Albertini B.. 6)Di sabatino M. 7)Corace G.. 8)Luppi B..
9)Canistro D..
University of Bologna
The bis (1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) is an innovative nonconventional
radical scavenger used with success in several disease models, such as inflammation,
neurological disorders, hepatitis and diabetes. To date, the main limit for the drug use is
represented by the intraperitoneal (i.p.) route of administration used in the pharmacological
treatments. In order to develop a delivery system that allowed both oral administration and the
therapeutic efficacy, Solid Lipid Microparticles (SLMs) containing a theoretical 18% w/w of IAC
have been produced. Recently, three formulations (A, B, C) have been tested at different dosages
in an inflammation and pain rat model. Inflammatory model was induced by the use of an
intraplantar injection of 100ml/paw of Freund's complete adjuvant (FCA). Administered per os at
different dosages, IAC B (60% stearic acid-20% Compritol® HD5 ATO) was the most efficient
formulation in reducing oedema and alleviating pain, compared to the gold standard Paracetamol.
Since the anti-diabetic effects of the i.p. formulation of IAC was already demonstrated in vivo, we
are now investigating the therapeutic efficacy of the selected (B) oral IAC formulation (SLMs) in
streptozotocin-nicotinamide diabetic mice
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
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
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
Investigating the physicochemical properties of solid dispersions based on semicrystalline carriers: A case study with ketoprofen
Full text linkHydrophilic semicrystalline carriers represent an alternative to amorphous polymers due to their low melting temperature, useful for the production of solid dispersions (SDs) by melting-based technologies. This research aims to compare SDs of ketoprofen (KET) and three different semicrystalline carriers (PEG, Poloxamer and Gelucire) regarding miscibility, phase behavior, molecular interactions and stability. KET was chosen owing to its low solubility and high glass forming ability. Estimation of drug-excipient miscibility was performed by Flory-Huggins theory. Negative Gibbs free energy indicated a spontaneous mixing of KET with the three carriers and miscibility in the order PEG > Poloxamer > Gelucire. SDs up to 40 % w/w of drug were produced by melting process at a temperature below KET melting point. Characterization of SDs was performed by differential scanning calorimetry, polarized light microscopy and powder X-ray diffraction. In case of PEG and Poloxamer, the drug incorporation did not affect carrier crystallinity, while KET was in the amorphous state. Differently, KET retarded the crystallization of Gelucire and at high drug loadings the SDs were amorphous and semisolid. FT-IR analysis revealed a strong interaction between KET and the three carriers. Finally, PEG-based SDs above 20 % KET loading displayed drug crystallization after 6 months of storage; while Poloxamer and Gelucire-based SDs showed KET crystallization only at 40 % KET. Due to its less hydrophilic character and limited water uptake, Gelucire showed the best stability among the three excipients
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
- …
