Background: A large number of new substances have insufficient biopharmaceutical properties for oral administration caused by their slow dissolution rate and poor solubility. Objective: The purpose of our experiment was to improve the physicochemical properties of a hydrophobic drug, quercetin, by the nanomilling approach. Methods: Quercetin nanosuspensions were prepared using a wet-milling method followed by lyophilization. Stabilizer type and ratio, drug content, milling time, and bead size were identified as critical variables, and their impacts on quercetin particle size were assessed. The optimized nanocrystal was characterized by its morphology, crystallinity, molecular interactions, saturation solubility, and dissolution properties. Results: At optimized process conditions of milling at 500 rpm for 18 cycles of grinding with 0.3 - 0.4 mm zirconium oxide beads, minimum particle size, and PDI values were 281.21 nm and 0.22, respectively. Nanocrystals showed rod-like nanostructures, and XRD scans confirmed a decrease in drug crystallinity. The optimized formulation showed increased solubility and dissolution rate, as well as good physical stability. Conclusions: Particle size reduction by media milling technique was an efficient method for the solubility enhancement of hydrophobic drugs.

Current study intended to prepare and evaluate phospholipid-based, mixed micelles (MMs) to improve the ocular delivery of posaconazole (POS), a broad-spectrum antifungal drug. For this, MMs based on egg phosphatidylcholine (EPC), as the main component, in combination with various bile salts (sodium cholate (NaC), sodium deoxycholate (NaDC), sodium taurocholate (NaTC)) or non-ionic surfactants (Pluronic® F-127, Pluronic® F-68, Tween 80, Labrasol® ALF, and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)) were prepared. Particle size, polydispersity index, zeta potential and entrapment efficiency were evaluated to optimize the composition and preparation method of the MMs. Finally, morphology, stability, in vitro release pattern, and in vitro antifungal activity of the optimized formulation were investigated. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30, prepared by the thin-film hydration method, showed more appropriate features. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30 showed more appropriate features, including an entrapment efficiency (EE) greater than 80%, spherical shape morphology, an average particle size of about 58 nm, desirable stability over a month, slow-release without a noticeable initial burst, and a significantly higher in vitro antifungal activity in comparison with the drug suspension. Therefore, this formulation was selected as the optimal MMs and could be considered as a promising carrier for topical ocular delivery of POS.

Background: Amphotericin B (AmB) is the first-line drug to treat invasive fungal infections. However, its delivery to the body and clinical use faces many challenges because of its poor solubility, poor pharmacokinetics, and severe nephrotoxicity. Objectives: Due to the necessity for designing safer and more effective nanocarriers for AmB and the importance of preclinical pharmacokinetic studies in evaluating these novel drug delivery systems, the present study was framed to explore the influence of rat strain on the pharmacokinetic profile of this drug. Methods: Twenty-four Wistar and Sprague–Dawley (SD) rats were intravenously injected with 1 mg/kg AmB as Fungizone or AmBisome, which are the two most commonly marketed formulations of the drug. Blood samples were collected before and at regular intervals up to 24 h after administration. Drug concentration was analyzed by a validated HPLC method, and pharmacokinetic parameters were determined by the non-compartmental method. Results: Irrespective of the type of formulation, the AUC0-t and AUC0-∞ values were significantly higher (P < 0.001), and Cl as an important PK parameter was markedly lower (P < 0.001) in SD rats compared to the Wistar strain. For Fungizone, the mean Cl values in SD and Wistar rats were 206.90 and 462.95 mL/h/kg (P < 0.001), respectively. The apparent volume of distribution (Vss) was also lower in SD rats compared to Wistar; however, for AmBisome, the difference in Vss was not statistically significant. Our further investigation suggested that the higher amount of total protein in the SD strain may justify the higher plasma concentrations and lower Cl and Vss of amphotericin B in this strain compared to the Wistar strain. Conclusions: Overall, following intravenous administration of AmB, there were significant differences in the pharmacokinetic parameters of the drug between two rat strains for both formulations. The obtained data is important for correctly interpreting experimental data from different research groups.