Development and characterization of the voriconazole loaded lipid-based nanoparticles.

The number of topical fungal infections is growing, mostly owing to immunosuppressive therapy. Several topical fungal infections, such as eye mycoses, can be treated by local administration of antimycotic drugs. One major group of the antifungal agents is triazole, such as voriconazole (VCZ), which is used as the first line treatment of aspergillosis. A disadvantage of VCZ is its low water solubility making the drug difficult to administer in a liquid preparation. The lipid-based nanoparticles (LNP) have attracted increasing attention due to their advantageous properties. Contrarily to the conventional carrier systems, LNP can improve the poor solubility of topically used drugs, such as VCZ. Therefore, LNP represents promising alternatives to traditional carrier systems. The aim of the study was to formulate VCZ loaded lipid-based nanoparticles (VCZ-LNP) by high pressure homogenization (HPH). The developed LNPs were characterized by particle size analysis, IR spectroscopy, differential scanning calorimetry, dialysis test and antifungal efficacy studies. The particle size of the optimized nanoparticles from the selected lipid base, Witepsol® W35, was 182±4.1nm after five cycles of homogenization at 600bar. The antifungal study confirmed that the optimized VCZ-LNP inhibited the fungus reproduction.

Development and characterization of voriconazole loaded nanoparticles for parenteral delivery.

Human serum albumin (HSA) has attracted the most attention in the last decades as a new nanocarrier system of active pharmaceutical ingredients (API) due to its biocompatibility and high binding capacity to hydrophobic drugs. Voriconazole (VCZ), an antifungal agent with low water solubility, was selected to produce albumin based nanoparticles using nanoparticle albumin-bound technology (nab™-technology). Aim of our study was to study the development process of VCZ-loaded nanoparticles for parenteral drug delivery, such as homogenizing pressure, homogenizing cycle number and drug loading capacity. The main characters of nanoparticles such as particle size distribution and polydispersity index (PDI) were determined by dynamic light scattering. Six homogenization cycles at 1800bar were ensured the acceptable PDI value (lower than 0.3) of the VCZ content nanoparticles. Optimized formulation process produced 81.2±1nm average particle size which meets the requirements of intravenous administration. Furthermore, the encapsulated concentration of VCZ was 69.7±4.2% and the water solubility was over 2 times greater than the API itself which were determined by the developed HPLC method. The in vivo release behavior can be predicted from our applied in vitro dissolution study. Almost 50% of VCZ was liberated from the nanoparticles in the first 60min.

A Lipid Base Formulation for Intramuscular Administration of a Novel Sulfur Donor for Cyanide Antagonism.

This study represents a new formulation of the novel Cyanide (CN) antidote, Dimethyl trisulfide (DMTS), for intramuscular administration. This is a naturally occurring organosulfur molecule with the capability of reacting with CN more efficiently than the present sulfur donor type CN therapy of Thiosulfate (TS). Two types of micelles (PEG2000-DSPE and PEG2000-DSPE/TPGS) were prepared and tested for their ability to encapsulate the liquid, highly lipophilic and volatile drug, DMTS. The micellar encapsulation for DMTS does not only eliminate the possible muscle necrosis at the injection sites, but the rate of evaporation within the micelles is suppressed, that can provide a level of stability for the formulation. The method of micelle preparation was optimized and it was demonstrated that the PEG2000-DSPE preparation can dissolve up to 2.0 mg/ml of the antidote candidate. Keeping the injection volume minimized this could provide a maximum DMTS dose of 12.5 mg/kg. However, even this low dose of DMTS showed a remarkable in vivo therapeutic efficacy (2 X LD50 protection) in a mice model when injected intramuscularly. These in vitro and in vivo findings proved the efficacy of DMTS in combating CN intoxication, and the presented work gives valuable insight to micelle preparation and sets the bases for a more advanced future formulation of DMTS.

[In vivo effect of food on absorption of fluoroquinolones]. / Fluorokinolonok in vivo étel-interakciós vizsgálatai.

Although food-drug interactions have been studied extensively in recent years, in the light of the complex nature of these interactions general guideline for clinical practice can not be given. Drug interactions with food (containing multivalent metal ions or protein) can have an influence on drug absorption with widely variety of mechanism, resulting in changes in both the rate and extent of bioavailability. Food-drug interaction can be important in the clinical practice. Studies of the interaction between food/juice and fluoroquinolones have produced conflicting results. A number of studies give evidence that fluoroquinolones forming slightly soluble complex with metal ions of food show reduced bioavailability. In the same time, concurrent ingestion of food/ juice with fluoroquinolones has been shown not to interfere with their absorption to a clinically significant degree.