Factorial design, physicochemical characterisation and activity of ciprofloxacin-PLGA nanoparticles

Poly(lactide-co-glycolide) nanoparticles incorporating ciprofloxacin HCl were prepared by means of a W/O/W emulsification solvent evaporation method. The stabiliser selected was poly(vinylalcohol). A 2(4) full factorial design based on four independent variables was used to plan the experiments and the variable parameters were the number of homogenisation cycles, addition of boric acid to the inner water phase containing the drug, ciprofloxacin concentration in the inner water phase and oil:outer water phase ratio. The effects of these parameters on the particle size, zeta potential, drug loading efficiency and drug release were investigated. Also the effect of gamma irradiation on the particle size and drug release was evaluated and DSC and XRD analyses of the compounds and the nanoparticles were performed. The activity on two series of microorganisms, Pseudomonas aeruginosa and Staphylococcus aureus, was examined.status: publishe

Use of ordered mesoporous silica to enhance the oral bioavailability of ezetimibe in dogs

The aim of this study was to investigate the bioavailability enhancement of the biopharmaceutics classification system class II compound ezetimibe loaded in ordered mesoporous silica (OMS) in dogs. The OMS was characterized as highly ordered mesoporous material with a narrow pore size distribution. Ezetimibe was loaded in OMS via incipient wetness impregnation to obtain a 20% (w/w) drug load, characterized by nitrogen adsorption and differential scanning calorimetry, and formulated in one capsule and two tablet formulations. Physicochemical characterization of loaded OMS indicated that ezetimibe molecules were molecularly deposited on the hydrophilic surface of the OMS. Two in vitro dissolution experiments were performed at 37°C in simulated gastric fluid with 0.1% sodium lauryl sulfate or Tween 80 to determine the drug release. All concepts were compared in vitro and in vivo with the commercially available tablet Ezetrol®. A dog study was designed to determine the oral bioavailability of ezetimibe capsules and tablets. The tablet preparations showed similar results to that of Ezetrol®. The capsule formulation demonstrated a faster absorption into the blood circulation, including a superior metabolization of ezetimibe into the active glucuronide conjugate. In vivo evaluation in dogs confirmed the improvement of ezetimibe absorption with the use of OMS as drug delivery technology.status: publishe

Evaluation of hop (Humulus lupulus) as a repellent for the management of Drosophila suzukii

status: Published onlin

Trace Level Detection and Quantification of Crystalline Silica in an Amorphous Silica Matrix with Natural Abundance Si-29 NMR

A protocol for the detection of trace amounts of quartz in amorphous silica gels by NMR spectroscopy was developed and tested on commercially available samples. Using natural abundance 29Si MAS NMR spectroscopy with CPMG acquisition and standard addition of crystalline quartz, quantitative detection of quartz concentrations down to 0.1% wt. was achieved. CPMG permitted to suppress the amorphous silica-derived signal, benefitting from the extremely long T2 relaxation time of quartz in 29Si and hence dramatically increasing the sensitivity. Dedicated post-processing exploiting the known CPMG spikelet frequencies allowed to probe the near-absence of quartz in commercial, 100% silica samples, enabling assessment of conformity of unknown samples to EU legislation (REACH).status: publishe

Magneto-Hydrodynamic Mixing: a New Technique for Preparing Carbomer Hydrogels

Magnetohydrodynamic mixing was evaluated as an alternative to conventional high shear mixing in the preparation of carbomer hydrogels containing 1.22 wt.% Carbopol® 980 NF. Neutralization of the carbomer dispersion (pH = 2.74) with triethanolamine (TEA) enabled to adjust the pH of the mixture and tune the viscosity of the hydrogel. Using high shear mixing, this approach was limited to 0.2 wt.% TEA (pH = 3.83) as the gel became too viscous and the recirculation flow dropped from 12 to 0.3 m3/h. Magnetohydrodynamic mixing enabled to reach TEA concentrations up to 1.0 wt.% (pH = 5.31). Apparent viscosity measurements on samples having 0.2 wt.% TEA revealed lower viscosities for carbomer hydrogels prepared with high shear mixing, i.e. 6,800 mPa·s versus 8,800 mPa for magneto-hydrodynamic mixing. Based on 1H NMR evidence, this decrease in apparent viscosity was attributed to structural damage to the carbomer backbone in combination with mechanochemical degradation of the added TEA

In Vivo Performance of Fenofibrate Formulated With Ordered Mesoporous Silica Versus 2-Marketed Formulations: A Comparative Bioavailability Study in Beagle Dogs

The present study aims to evaluate the in vitro and in vivo performance of ordered mesoporous silica (OMS) as a carrier for the poorly water-soluble compound fenofibrate. Fenofibrate was loaded into OMS via incipient wetness impregnation to obtain a 29% drug load and formulated into capsules. Two capsule dosage forms (containing 33.5 and 16.75 mg fenofibrate, respectively) were compared with the commercially available forms-Lipanthyl (R) (fenofibrate microcrystals) and Tricor (R) (fenofibrate nanocrystals). In vitro dissolution tests showed that the amount of fenofibrate released from Lipanthyl (R) and Tricor (R) was approximately 30%, whereas approximately 66% and 60% of the drug was released from OMS capsules containing 33.5 and 16.75 mg of fenofibrate, respectively. Storage of OMS capsules loaded with 33.5 mg of fenofibrate at 25 degrees C/60% relative humidity (RH) or 40 degrees C/75% RH did not alter the release kinetics, nor the physical state of the compound, pointing the stability of the present formulation. The in vivo study in dogs confirmed satisfying level of safety and tolerability of fenofibrate-OMS formulation (eq. 33.5 mg) with the potential to improve the absorption of fenofibrate. Though some variability in the data, this formulation is promising to be further investigated in a clinical trial setting

Ordered mesoporous silica to enhance the bioavailability of poorly water-soluble drugs: Proof of concept in man

Formulating poorly water soluble drugs using ordered mesoporous silica materials is an emerging approach to tackle solubility-related bioavailability problems. The current study was conducted to assess the bioavailability-enhancing potential of ordered mesoporous silica in man. In this open-label, randomized, two-way cross-over study, 12 overnight fasted healthy volunteers received a single dose of fenofibrate formulated with ordered mesoporous silica-or a marketed product based on micronized fenofibrate. Plasma concentrations of fenofibric acid, the pharmacologically active metabolite of fenofibrate, were monitored up to 96 h post-dose. The rate (C-max/dose increased by 77%; t(max) reduced by 0.75 h) and extent of absorption (AUC(0-24h)/dose increased by 54%) of fenofibrate were significantly enhanced following administration of the ordered mesoporous silica based formulation. The results of this study serve as a proof of concept in man for this novel formulation approach