Self-nanoemulsifying drug delivery system to improve transcorneal permeability of voriconazole: in-vivo studies.

OBJECTIVE: This study investigates the effectiveness of self-nanoemulsifying drug delivery system (SNEDDS) in improving voriconazole transcorneal permeability. METHODS: Voriconazole-SNEDDS was prepared with isopropyl myristate, PEG 400, Tween 80® and Span 80® and was subjected for physicochemical characterization after reconstitution with NaCl 0.9% (1/9; v/v). In-vitro antifungal activity was assessed and compared with the marketed formulation. In-vivo studies, namely ocular irritation test via modified Draize test and pharmacokinetic study, were investigated using rabbit as animal model. KEY FINDINGS: Voriconazole-SNEDDS presented a droplet size of 21.353 ± 0.065 nm, a polydispersity index of 0.123 ± 0.003, a pH of 7.205 ± 0.006 and an osmolarity of 342.667 ± 2.517 mOsmol/l after reconstitution with NaCl 0.9%. Voriconazole-SNEDDS minimum inhibitory concentration (MIC90 ) was similar to the one of marketed formulation for Candida species while it was significantly lower (P < 0.001) for Aspergillus fumigatus. Draize test revealed that Voriconazole-SNEDDS was safe for ocular administration. Voriconazole maximum concentration (5.577 ± 0.852 µg/ml) from SNEDDS was higher than marketed formulation (Cmax  = 4.307 ± 0.623 µg/ml), and the Tmax was delayed to 2 h. The area under the concentration-time curve value of Voriconazole-SNEDDS was improved by 2.419-fold. CONCLUSION: Our results suggest that SNEDDS is a promising carrier for voriconazole ocular delivery and this encourages further clinical studies.

Voriconazole-loaded self-nanoemulsifying drug delivery system (SNEDDS) to improve transcorneal permeability.

The aim of this study was to develop self- nanoemulsifying drug delivery system (SNEDDS) to improve the transcorneal permeability of voriconazole. A 'mixture design around a reference mixture' approach was applied. This latter included four components, namely, isopropyl myristate, PEG 400, Tween® 80 and Span® 80 as oil, co-solvent, surfactant and co-surfactant, respectively. Droplet size was selected as response. The effect of mixture components on droplet size was analyzed by means of response trace method. Optimal formulation was subjected to stability studies and characterized for droplet size, polydispersity index (PDI), pH, osmolarity, viscosity and percentage of transmittance. Ex-vivo transcorneal permeation of the optimal and the marketed formulations was carried out on excised bovine cornea using Franz cell diffusion apparatus. Optimal voriconazole loaded-SNEDDS showed moderate emulsification efficiency and was characterized by a droplet size of 21.447 ± 0.081 nm, a PDI of 0.156 ± 0.004, a pH of 7.205 ± 0.006, an osmolarity of 310 mosmol/Kg and a viscosity of 8.818 ± 0.076 cP. Moreover, it presented an excellent stability and exhibited a significant improvement (p < 0.05) in apparent permeability coefficient (1.982 ± 0.187 × 10-6 cm/s) when compared to commercialized formulation (1.165 ± 0.106 × 10-6 cm/s). These results suggest that SNEDDS is a promising carrier for voriconazole ocular delivery.

Nanoprecipitation process: From encapsulation to drug delivery.

Drugs encapsulation is a suitable strategy in order to cope with the limitations of conventional dosage forms such as unsuitable bioavailability, stability, taste, and odor. Nanoprecipitation technique has been used in the pharmaceutical and agricultural research as clean alternative for other drug carrier formulations. This technique is based on precipitation mechanism. Polymer precipitation occurs after the addition of a non-solvent to a polymer solution in four steps mechanism: supersaturation, nucleation, growth by condensation, and growth by coagulation that leads to the formation of polymer nanoparticles or aggregates. The scale-up of laboratory-based nanoprecipitation method shows a good reproducibility. In addition, flash nanoprecipitation is a good strategy for industrial scale production of nanoparticles. Nanoprecipitation is usually used for encapsulation of hydrophobic or hydrophilic compounds. Nanoprecipitation was also shown to be a good alternative for the encapsulation of natural compounds. As a whole, process and formulation related parameters in nanoprecipitation technique have critical effect on nanoparticles characteristics. Biodegradable or non-biodegradable polymers have been used for the preparation of nanoparticles intended to in vivo studies. Literature studies have demonstrated the biodistribution of the active loaded nanoparticles in different organs after administration via various routes. In general, in vitro drug release from nanoparticles prepared by nanoprecipitation includes two phases: a first phase of "burst release" which is followed by a second phase of prolonged release. Moreover, many encapsulated active molecules have been commercialized in the pharmaceutical market.

Polycaprolactone Based Nanoparticles Loaded with Indomethacin for Anti-Inflammatory Therapy: From Preparation to Ex Vivo Study.

PURPOSE: This work focused on the preparation of polycaprolactone based nanoparticles containing indomethacin to provide topical analgesic and anti-inflammatory effect for symptomatic treatment of inflammatory diseases. Indomethacin loaded nanoparticles are prepared for topical application to decrease indomethacin side effects and administration frequency. Oppositely to already reported works, in this research non-invasive method has been used for the enhancement of indomethacin dermal drug penetration. Ex-vivo skin penetration study was carried out on fresh human skin. METHODS: Nanoprecipitation was used to prepare nanoparticles. Nanoparticles were characterized using numerous techniques; dynamic light scattering, SEM, TEM, DSC and FTIR. Regarding ex-vivo skin penetration of nanoparticles, confocal laser scanning microscopy has been used. RESULTS: The results showed that NPs hydrodynamic size was between 220 to 245 nm and the zeta potential value ranges from -19 to -13 mV at pH 5 and 1 mM NaCl. The encapsulation efficiency was around 70% and the drug loading was about 14 to 17%. SEM and TEM images confirmed that the obtained nanoparticles were spherical with smooth surface. The prepared nanoparticles dispersions were stable for a period of 30 days under three temperatures of 4°C, 25°C and 40°C. In addition, CLSM images proved that obtained NPs can penetrate the skin as well. CONCLUSION: The prepared nanoparticles are submicron in nature, with good colloidal stability and penetrate the stratum corneum layer of the skin. This formulation potentiates IND skin penetration and as a promising strategy would be able to decline the side effects of IND.

Encapsulation of NSAIDs for inflammation management: Overview, progress, challenges and prospects.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed drugs. Debilitating diseases such as rheumatoid arthritis and osteoarthritis are commonly managed by NSAIDs. However, NSAIDs pharmacological mechanism is often associated with the presence of gastrointestinal side effects. NSAIDs encapsulation is performed in order to overcome some of the drawbacks linked to their clinical use. To fulfill this purpose, various vectors like polymer-based nanoparticles, liposomes and solid lipid nanoparticles have been proposed. Such vehicles could have advantages but some limitations as well. This manuscript highlights current NSAIDs encapsulation approaches based on either preformed polymers or lipids. Moreover, properties of the prepared carriers and their applications are also discussed. Many factors are taken into account for selecting carrier type and encapsulation method. It was concluded that different vehicles and preparation methods have been employed for NSAIDs encapsulation. Mostly, vehicles sizes ranged within the nanoscale. Main advantages that have been confirmed by in vitro and in vivo studies include promoted stability, sustained release and bioavailability enhancement.