Dissipative Particle Dynamics Investigation of the Transport of Salicylic Acid through a Simulated In Vitro Skin Permeation Model.

Permeation models are often used to determine diffusion properties of a drug through a membrane as it is released from a delivery system. In order to circumvent problematic in vivo studies, diffusion studies can be performed in vitro, using (semi-)synthetic membranes. In this study salicylic acid permeation was studied, employing a nitrocellulose membrane. Both saturated and unsaturated salicylic acid solutions were studied. Additionally, the transport of salicylic acid through the nitrocellulose membrane was simulated by computational modelling. Experimental observations could be explained by the transport mechanism that was revealed by dissipative particle dynamics (DPD) simulations. The DPD model was developed with the aid of atomistic scale molecular dynamics (AA-MD). The choice of a suitable model membrane can therefore, be predicted by AA-MD and DPD simulations. Additionally, the difference in the magnitude of release from saturated and unsaturated salicylic acid and solutions could also be observed with DPD. Moreover, computational studies can reveal hidden variables such as membrane-permeant interaction that cannot be measured experimentally. A recommendation is made for the development of future model permeation membranes is to incorporate computational modelling to aid the choice of model.

Tolerance and growth kinetics of bacteria isolated from gold and gemstone mining sites in response to heavy metal concentrations.

Response and growth kinetics of microbes in contaminated medium are useful indices for the screening and selection of tolerant species for eco-friendly bio-augmentative remediation of polluted environments. In this study, the heavy metal (HM) tolerance, bioaccumulation and growth kinetics of seven bacterial strains isolated from mining sites to 10 HMs (Cd, Hg, Ni, Al, Cr, Pb, Cu, Fe, Mn and Zn) at varied concentrations (25-600 mgL-1) were investigated. The isolates were phylogenetically (16S rRNA gene) related to Lysinibacillus macroides, Achromobacter spanius, Bacillus kochii, B. cereus, Klebsiella pneumoniae, Pseudomonas mosselii and P. nitroreducens. Metal tolerance, effects on lag phase duration and growth rates were assessed using the 96-well micro-titre method. Furthermore, metal bioaccumulation and quantities within cells were determined by transmission electron microscopy and electron dispersive x-ray analyses. Tolerance to Ni, Pb, Fe and Mn occurred at highest concentrations tested. Growth rates increased with increasing Fe concentrations, but reduced significantly (p < .05) with increasing Zn, Cu, Hg, Cd and Al. Significantly higher (p < .05) growth rates (compared to controls) was found with some isolates in Hg (25 mgL-1), Ni (100 mgL-1), Cr (150 mgL-1), Mn (600 mgL-1), Pb (100 mgL-1), Fe (600 mgL-1) and Al (50 mgL-1). Lag phase urations were isolate- and heavy metal-specific, in direct proportion to concentrations. A. spanius accumulated the most Mn and Zn, while B. cereus accumulated the most Cu. Metals accumulated intra-cellularly without cell morphology distortions. The isolates' multi-metal tolerance, intra-cellular metal bioaccumulation and growth kinetics suggest potentials for application in the synergetic biodegradation and bioremediation of polluted environments, especially HM-rich sites.

Preparation and characterization of highly porous direct compression carrier particles with improved drug loading during an interactive mixing process.

The aim of this study was to prepare highly porous carrier particles by emulsion solvent evaporation and compare the loading capacity of these beads with two traditional carriers, sugar beads, and microcrystalline cellulose granules during an interactive mixing process. The porous carrier particles were prepared by an emulsion solvent evaporation process using cellulose propionate as a binder, anhydrous dibasic calcium phosphate, and ion exchange resins as a fillers, and polyethylene glycol as a pore inducer. Micronized furosemide or griseofulvin powder was mixed with the same volume of each carrier in an interactive mixing process. The tableting properties, drug loading per unit volume of carrier, content uniformity of the mixtures, and dissolution of the drugs from the mixtures were measured. The results showed that highly porous microcapsules with desirable hardness equivalent to that of sugar beads and MCC granules were successfully prepared. On average the loading capacity of the new carrier was 310% that of sugar beads and 320% that of MCC granules during an interactive mixing process with very good content uniformity. The tableting properties of the microcapsules were equivalent to that of microcrystalline cellulose granules, and the dissolution of the drugs from interactive mixtures prepared with the new carrier was equivalent to that of drug suspensions. This showed that the prepared microcapsule carrier could be used to improve the loading capacity during an interactive mixing and to prepare tablets by direct compression.

Nanoparticle multilayers: surface modification of photosensitive drug microparticles for increased stability and in vitro bioavailability.

The results of this study report the novel use of electrostatic layer-by-layer nanoassembly of biocompatible nanoparticulate TiO2 multilayers to coat irregular nifedipine (NF) microcrystals to increase the photostability of the drug when exposed to simulated sunlight and to increase the dissolution rate and possibly the bioavailability of the drug after oral administration. The photostability of NF microcrystals (35 microm) coated with multiple bilayers of positively charged PDDA and negatively charged nanosized TiO2 particles (20-25 nm) was measured when exposed to an illuminance of 12 W/m2 corresponding to a light dose of 30 k lux or 25 W/m2 corresponding to light dose of 60 k lux. The dissolution rate of nifedipine from the coated microcrystals was measured in simulated gastric fluid containing 0.05% w/v polysorbate 80. Coating with one TiO2 layer increased the shelf life of nifedipine by 30 hours independent of the intensity of the light exposure. With an increase in the number of TiO2 layers; the photostability of the drug was enhanced even more. A TiO2 monolayer decreased the contact angle by 20 degrees for water and 33 degrees for the dissolution medium as compared with uncoated NF surfaces. This increase in wettability due to a decrease in contact angle increased the dissolution rate of nifedipine microcrystals coated with 1 PDDA/TiO2 bilayer 13-fold after 10 minutes, 5-fold after 1 hour, and 2-fold after 12 hours when compared to uncoated microcrystals. It is assumed that TiO2 increased the photostability because the nanoparticulate multilayers acts as a potential filter protecting the drug from damaging light rays reaching the drug crystals. The dissolution rate was increased because the hydrophilic TiO2 nanoparticles increased the aqueous wettability of the drug crystals thereby preventing aggregation in the dissolution medium. This ensured that the maximum drug surface area was exposed to the dissolution medium.