Stability of an ophthalmic micellar formulation of cyclosporine A in unopened multidose eyedroppers and in simulated use conditions.

Cyclosporine A eye drops are used at concentrations ranging from 0.5 to 20mg/mL to treat a variety of ophthalmic diseases. Cyclosporine A formulations at high concentrations are difficult to manufacture because of cyclosporine's lipophilicity, and generally require an oil based vector. In this study, we investigated the physicochemical and microbiological stability of two high concentrations (10mg/mL and 20mg/mL) of an ophthalmic cyclosporine A micellar solution in a low density polyethylene multidose eyedropper, at two conservation conditions (5°C and 25°C), before and with simulated use. Analyses used were the following: visual inspection, cyclosporine quantification by a stability-indicating liquid chromatography method, osmolality and pH measurements and turbidity. A complementary analysis by dynamic light scattering was implemented to evaluate potential particle formation or micelle size change. In the in-use study, cyclosporine quantification was also performed on the drops emitted from the multidose eyedroppers. Our results show that the cyclosporine micellar formulation retains good physicochemical and microbiological stability, as all parameters stayed within acceptable range limits, however a higher variability in cyclosporine concentrations was observed for 20mg/mL units stored at 25°C. The in-use study showed that cyclosporine concentrations in the emitted drops were also within acceptable range limits. The micellar formulation presented in this study can therefore be stored at 5°C or at ≤25°C for up to 6months.

In vitro evaluation of TiO2 nanotubes as cefuroxime carriers on orthopaedic implants for the prevention of periprosthetic joint infections.

CONTEXT: The prevention of periprosthetic joint infections requires an antibiotic prophylactic therapy, which could be delivered locally using titanium dioxide nanotubes as novel reservoirs created directly on the orthopaedic implant titanium surface. OBJECTIVE: In this study, the influence of several parameters that could impact the use of titanium dioxide nanotubes as cefuroxime carriers was investigated. METHOD: Cefuroxime loading and release was studied for 90 min with three nano-topography conditions (nano-smooth, nano-rugged and nano-tubular), two cefuroxime loading solution concentrations (150 mg/mL and 25mg/mL) and two nano-tubular crystalline structures. RESULTS: In all tested conditions, maximum amount of cefuroxime was obtained within 2 min. For both cefuroxime loading solution concentrations, nano-smooth samples released the least cefuroxime, and the nano-tubular samples released the most, and a six-fold increase in the concentration of the cefuroxime loading increased the amount of cefuroxime quantified by more than seven times, for all tested nano-topographies. However, the nano-tubes' crystalline structure did not have any influence on the amount of cefuroxime quantified. CONCLUSION: The results demonstrated that the surface nano-topography and loading solution concentration influence the efficiency of titanium dioxide nanotubes as cefuroxime carriers and need to be optimized for use as novel reservoirs for local delivery of cefuroxime to prevent periprosthetic infections.

Nanoporous surface wetting behavior: the line tension influence.

The aim of this work is to develop a physical model to describe the evolution of the apparent contact angle for four different liquids on nanotextured alumina surfaces with different pore radius. The nanoporous alumina templates were fabricated by anodization of Al foil in a 0.3 M oxalic acid solution. Scanning electron microscopy was used to characterize the morphology of the surfaces. The templates are approximately 400 nm in thickness and consist of a well-ordered hexagonal array of uniform radius pores spaced 105 nm apart with pore radii from 12 to 42 nm. The wettability of nanoporous alumina templates was investigated using contact-angle measurements. We measured the contact angles using four liquids: water, ethylene glycol, aniline, and a mixture of ethylene glycol and aniline. We developed a new theoretical model for the contact angle on nanoporous surfaces as a function of the pore radius. This model is based on energy considerations and involves liquid penetration into the nanopores driven by the capillarity (Laplace's law). Because the air is compressed inside the pores, this model also includes the effect of the line tension. This is important because the three-phase line length is greatly enhanced in our nanoporous structures. For example: for a millimeter-sized droplet, the three-phase line around the perimeter of the droplet is a few millimeters long, whereas the total three-phase line within the pores can reach several tens of meters. Using our model, the line-tension value for our nanopore samples is positive and ranges from 4 to 13 × 10(-9) N, which falls within the wide interval from 10(-11) to 10(-5) N quoted in the literature. Nanoporous surfaces may allow the effect of line tension to be visible for micro- to macrodroplets.