1,721,056 research outputs found
Bioavailability of metoclopramide from a new chewing gum device
No full textMetoclopramide is widely used for treatment of nausea. Development of metoclopramide as a
medicated chewing gum has the potential advantage related to patient compliance, fast onset of
effect and improved bioavailability. In this study, bioavailability of metoclopramide from a new
chewing gum device, 3TabGum® was evaluated in healthy volunteers. Medicated chewing gum was
well tolerated in all subjects. Compared to immediate release tablet, AUC following administration
of chewing gum was higher (224.91 vs. 166.53 ng h/ml), while tmax was smaller (1.38 vs. 1.88 h),
suggesting improved bioavailability and rapid onset of drug absorption. However, absorption rate
was lower, as evidenced by lower Cmax (17.23 vs. 20.80 ng/ml). Terminal half-life was prolonged
(11.58 vs. 5.35 h), implying that initial fast release of metoclopramide is followed by much slower
release of the remaining smaller portion of the drug. These results indicate that chewing gum is a
promising alternative to current metoclopramide formulations
Development and preclinical pharmacokinetics of a novel subcutaneous thermoresponsive system for prolonged delivery of heparin
Full text linkHeparin is still widely used for treatment and prevention of thromboembolic diseases. Due to specific physicochemical properties, it requires frequent parenteral injections. In this study we present the development and in vitro evaluation of an advanced delivery system for prolonged subcutaneous release of heparin. The delivery system consisted of an in situ forming thermoresponsive poloxamer-based platform combined with pH-responsive polyelectrolyte heparin/chitosan nanocomplexes. Thermoresponsive hydrogels were tested for gelation temperature, gel dissolution and in vitro heparin release, whereas polyelectrolyte nanocomplexes were physico-chemically characterized, as well as tested for in vitro cytotoxicity and in vitro heparin release. Hydrogel combined of two poloxamers demonstrated the highest gelation temperature (28.6 C), while the addition of hydroxypropyl methylcellulose prolonged gel dissolution. On the other hand, nanocomplexes’ dispersions, prepared at 1:1 heparin/chitosan mass ratio and in the concentration range 0.375–1.875 mg/mL, demonstrated mean diameter 34 mV. Pharmacokinetics of selected formulations (thermoresponsive hydrogel, nanocomplexes and a dual system consisting of nanocomplexes incorporated into thermoresponsive
hydrogel) were studied in rats. Heparin plasma concentration-time profiles revealed a double-peak phenomenon, probably due to heparin diffusion inside the polymer matrix and gel dissolution. Pharmacokinetic parameters were determined by a non-linear mixed effects modeling approach. It was
demonstrated that thermoresponsive hydrogel with heparin/chitosan nanocomplexes enabled the lowest absorption rate of heparin into systemic circulation and provided heparin concentration above the prophylaxis threshold for 5 days. In situ gelling thermoresponsive matrix combined with chitosan nanocomplexes present a promising delivery system for heparin, requiring less frequent administration during long-term treatment
Bisoprolol pharmacokinetics and body composition in patients with chronic heart failure: a longitudinal study
No full textPharmacokinetics and immunomodulatory effect of lipophilic Echinacea extract formulated in softgel capsules
Full text linkAn attractive herbal product, softgel capsules containing 10 mg of Echinacea angustifolia lipophilic extract, was given in a single oral administration to 10 human volunteers to perform a pharmacokinetic and immunological study. The plasma concentration of the major constituent was monitored, quantifying at predetermined time points the dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamides (tetraene). The plasmatic levels of IL-2, IL-6, IL-8, IL-10 and TNF-a in samples collected before and 24 h after drug administration were analyzed by cytokine assay. The total RNA was extracted from limpho-monocyte isolated from the same blood samples and the same cytokines in terms of gene expression were evaluated. With the help of proper statistical tests the differences between the values obtained at 0 and 24 h were evaluated. Results of pharmacokinetic studies attest an approximately 3.5-fold improvement of tetraene oral bioavailability compared with previously published studies. Dodeca-2E,4E-dienoic acid isobutylamide exerts immunomodulatory effects down-regulating the gene expression and reducing the protein plasmatic levels of pro-inflammatory cytokines such as IL-6, TNF-a and IL-8, and up-regulating the expression of anti-inflammatory molecules as IL-10. Student’s two-sided paired t-test and non-parametric
Wilcoxon–Mann–Whitney signed rank test agree in the conclusions about the differences between the ln values at 24 h and corresponding ln values at 0 h
Natural Deep Eutectic Solvents (NADES) as a Tool for Bioavailability Improvement: Pharmacokinetics of Rutin Dissolved in Proline/Glycine after Oral Administration in Rats: Possible Application in Nutraceuticals
Full text linkThere is a need for innovation in plant-derived pharmaceuticals, food supplements and nutraceutical products regarding the use of more eco-sustainable solvents for their extraction. Furthermore, the poor oral bioavailability of several phytochemicals with health promoting effects stimulates the research in the field of pharmaceutical formulations. Natural Deep Eutectic Solvents (NADES) are formed by natural compounds, and can be considered as future solvents being especially useful for the preparation of nutraceuticals and food-grade extracts. In this paper various NADES were prepared using sugars, aminoacids and organic acids. Rutin (quercetin-3-O-α-l-rhamnopyranosyl-(1→6))-β-d-glucopyranose) was used as a model compound to study NADES. Moreover, the effect of various eutectic mixtures on rutin's water solubility was studied. Proline/glutamic acid (2:1) and proline/choline chloride (1:1) mixtures have a solubility comparable to ethanol. The proline/glutamic acid (2:1) eutectic containing rutin was used in a pharmacokinetic study in Balb/c mice while bioavailability was compared to oral dosing of water suspension. Plasmatic levels of rutin were measured by HPLC-MS/MS showing increased levels and longer period of rutin permanence in plasma of NADES treated animals. This paper reports the possible use of non-toxic NADES for pharmaceutical and nutraceutical preparations
Quality improvement of melt extruded laminar systems using mixture design
Full text linkThis study investigates the application of melt extrusion for the development of an oral retard formulation with a precise drug release over time. Since adjusting the formulation appears to be of the utmost importance in achieving the desired drug release patterns, different formulations of laminar extrudates were prepared according to the principles of Experimental Design, using a design for mixtures to assess
the influence of formulation composition on the in vitro drug release from the extrudates after 1 h and after 8 h. The effect of each component on the two response variables was also studied.
Ternary mixtures of theophylline (model drug), monohydrate lactose and microcrystalline wax (as
thermoplastic binder) were extruded in a lab scale vertical ram extruder in absence of solvents at a temperature
below the melting point of the binder (so that the crystalline state of the drug could be maintained),
through a rectangular die to obtain suitable laminar systems.
Thanks to the desirability approach and a reliability study for ensuring the quality of the formulation, a
very restricted optimal zone was defined within the experimental domain. Among the mixture components,
the variation of microcrystalline wax content played the most significant role in overall influence
on the in vitro drug release. The formulation theophylline:lactose:wax, 57:14:29 (by weight), selected
based on the desirability zone, was subsequently used for in vivo studies. The plasma profile, obtained
after oral administration of the laminar extruded system in hard gelatine capsules, revealed the typical
trend of an oral retard formulation.
The application of the mixture experimental design associated to a desirability function permitted to
optimize the extruded system and to determine the composition space that ensures final product quality.
2015 Elsevier B.V. All rights reserved
Improving Biopharmaceutical Properties of Vinpocetine Through Cocrystallization
Full text linkVinpocetine is a poorly water soluble weakly basic drug (pKa 1⁄4 7.1) used for the treatment of several cerebrovascular and cognitive disorders. Because existing formulations exhibit poor bioavailability and scarce absorption, a dosage form with improved pharmacokinetic properties is highly desirable. Cocrystallization represents a promising approach to generate diverse novel crystal forms and to improve the aqueous solubility and in turn the oral bioavailability. In this article, a novel ionic cocrystal of vinpocetine is described, using boric acid as a coformer, and fully characterized (by means of differential scanning calorimetry, solid-state nuclear magnetic resonance, powder and singlecrystal X-ray diffraction, and powder dissolution test). Pharmacokinetic performance was also tested in a human pilot study. This pharmaceutical ionic cocrystal exhibits superior solubilization kinetics and modulates important pharmacokinetic values such as maximum concentration in plasma (Cmax), time to maximum concentration (tmax), and area under the plasma concentration-time curve (AUC) of the poorly soluble vinpocetine and it therefore offers an innovative approach to improve its bioavailability
Optimization of the design of pediatric clinical trial with fentanyl using population pharmacokinetic-pharmacodynamic modelling and simulation
No full textA systematic review of assessment reports for granting marketing authorization of biosimilars in European Union
No full textEvaluation of the agreement between the results of electrochemiuminiscence immunoassay and microparticle enzyme immunoassay method aimed at determining gonadotropins and prolactin
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