Intravesical Treatments of Bladder Cancer: Review

For bladder cancer, intravesical chemo/immunotherapy is widely used as adjuvant therapies after surgical transurethal resection, while systemic therapy is typically reserved for higher stage, muscle-invading, or metastatic diseases. The goal of intravesical therapy is to eradicate existing or residual tumors through direct cytoablation or immunostimulation. The unique properties of the urinary bladder render it a fertile ground for evaluating additional novel experimental approaches to regional therapy, including iontophoresis/electrophoresis, local hyperthermia, co-administration of permeation enhancers, bioadhesive carriers, magnetic-targeted particles and gene therapy. Furthermore, due to its unique anatomical properties, the drug concentration-time profiles in various layers of bladder tissues during and after intravesical therapy can be described by mathematical models comprised of drug disposition and transport kinetic parameters. The drug delivery data, in turn, can be combined with the effective drug exposure to infer treatment efficacy and thereby assists the selection of optimal regimens. To our knowledge, intravesical therapy of bladder cancer represents the first example where computational pharmacological approach was used to design, and successfully predicted the outcome of, a randomized phase III trial (using mitomycin C). This review summarizes the pharmacological principles and the current status of intravesical therapy, and the application of computation to optimize the drug delivery to target sites and the treatment efficacy

Humanities for the Future: a new European Agenda

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Translational Medicine: Pharmacokinetic and Pharmacogenetic Aspects of Personalized Pharmacotherapy

Variability among individuals that affects clinical outcome is still one of the major challenges in drug development and in the practice of medicine. [...

EFFECT OF COMPOSITION ON THE RELEASE FROM MELT EXTRUDED LAMINAR SYSTEMS BY APPLICATION OF MIXTURE EXPERIMENTAL DESIGN

EFFECT OF COMPOSITION ON THE RELEASE FROM MELT EXTRUDED LAMINAR SYSTEMS BY APPLICATION OF MIXTURE EXPERIMENTAL DESIG

Bioavailability of metoclopramide from a new chewing gum device

5Metoclopramide is widely used in the treatment of nausea. The development of metoclopramide as medicated chewing gum has potential advantages in terms of 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 with immediate release tablets, AUC following administration of chewing gum was higher (224.9 vs. 166.5 ng h/mL), while t max 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 C max (17.2 vs. 20.8 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 formulationsnonemixedI.GRABNAR; L.MAGGI; M.COCCHIETTO; U.CONTE; VOINOVICH D.I., Grabnar; L., Maggi; M., Cocchietto; U., Conte; Voinovich, Dari

Preparation in high-shear mixer of sustained-release pellets by melt pelletisation

The preparation of sustained-release pellets by melt pelletisation was investigated in a 10-l high shear mixer and ternary mixtures containing stearic acid as a melting binder, anhydrous lactose as a filler and theophylline as a model drug. A translated Doehlert matrix was applied for the optimisation of process variables and quality control of pellets characteristics. After determination of size distribution, the pellets were characterised with scanning electron microscopy, X-ray photoelectron spectroscopy and porosimetric analysis. Finally, the in vitro release from every single size fraction was evaluated and the release mechanism was analysed. Since the drug release rate decreased when enhancing the pellet size fraction, the 2000-mm fraction, exhibiting a substantially zero-order release, was selected for further in vivo biovailability studies. These data demonstrated that pellets based on the combination of stearic acid and lactose can be used to formulate sustained release pellets for theophylline. \ua9 2000 Elsevier Science B.V. All rights reserved

An innovative oxytetracycline self-emulsifying formulation for fish diets: preparation,characterisation and oral bioavailability in Rainbow Trout (Oncorhyncus mykiss)and in EuropeanSea Bass (Dicentrarchus Labrax)

The aim of this study was to develop a self-emulsifying system (SES) with practical applications in fish farming. In particular, the lipid vehicle was developed in order to deliver oxytetracycline hydrocloride to rainbow trout (RT) and European sea bass (ESB) so as to improve the drug\u2019 s oral bioavailability. The developed formulation was assessed in comparison to an aqueous solution working with two fish species (one fresh-water and one salt-water), after oral administration with a gastric probe. Results indicated an enhancement of bioavailability of 5.86 and 5.41 times over the aqueous solution, in RT and ESB, respectively. SES was then used to prepare medicated feed containing the formulation. The pharmacokinetic of this feed was evaluated after oral administration and compared to that of commercial OTC medicated feed. The bioavailability of OTC delivered in SES was 3.2 times higher in RT and 2.7 times higher in ESB, than OTC supplied by commercial medicated feed. This bioavailability enhancement was confirmed when RT were fed by classical administration in fish tanks of single and repeated administration of OTC delivered in SES and commercial medicated feed, attesting to better absorption of the SES formulation

Preparation end in vitro/in vivo characterisation of melt pelletised paracetamol/stearic acid sustained release delivery system

The potential of a sustained release formulation for paracetamol produced by melt pelletisation was investigated. After the production of the pellets, based on the combination of stearic acid as a melting binder and anhydrous lactose as a filler, the 3000-2000 \u3bcm size fraction was selected in the light of the promising in vitro dissolution results for further characterisations, including scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), specific surface area and true density determination. Hence the release mechanism was analysed with the help of an appropriate mathematical model. The mathematical model was built on the hypotheses that drug diffusion and solid drug dissolution in the release environment are the key phenomena affecting drug release kinetics. Bioavailability of the developed formulation was evaluated in an in vivo study in eight subjects

An innovative oxytetracycline self-emulsifying formulation for fish diets: preparation, characterisation and oral bioavailability in rainbow trout (Oncorhyncus mykiss) and in European sea bass (Dicentrarchus labrax)

The aim of this study was to develop a self-emulsifying system (SES) with practical applications in fish farming. In particular, the lipid vehicle was developed in order to deliver oxytetracycline hydrocloride to rainbow trout (RT) and European sea bass (ESB) so as to improve the drug\u2019 s oral bioavailability. The developed formulation was assessed in comparison to an aqueous solution working with two fish species (one fresh-water and one salt-water), after oral administration with a gastric probe. Results indicated an enhancement of bioavailability of 5.86 and 5.41 times over the aqueous solution, in RT and ESB, respectively. SES was then used to prepare medicated feed containing the formulation. The pharmacokinetic of this feed was evaluated after oral administration and compared to that of commercial OTC medicated feed. The bioavailability of OTC delivered in SES was 3.2 times higher in RT and 2.7 times higher in ESB, than OTC supplied by commercial medicated feed. This bioavailability enhancement was confirmed when RT were fed by classical administration in fish tanks of single and repeated administration of OTC delivered in SES and commercial medicated feed, attesting to better absorption of the SES formulation