Nanosuspensions (NSs), which are nanosized colloidal particle systems, have recently become one of the most interesting substances in nanopharmaceuticals. NSs have high commercial potential because they provide the enhanced solubility and dissolution of low-water-soluble drugs by means of their small particle sizes and large surface areas. In addition, they can alter the pharmacokinetics of the drug and, thus, improve its efficacy and safety. These advantages can be used to enhance the bioavailability of poorly soluble drugs in oral, dermal, parenteral, pulmonary, ocular, or nasal routes for systemic or local effects. Although NSs often consist mainly of pure drugs in aqueous media, they can also contain stabilizers, organic solvents, surfactants, co-surfactants, cryoprotectants, osmogents, and other components. The selection of stabilizer types, such as surfactants or/and polymers, and their ratio are the most critical factors in NS formulations. NSs can be prepared both with top-down methods (wet milling, dry milling, high-pressure homogenization, and co-grinding) and with bottom-up methods (anti-solvent precipitation, liquid emulsion, and sono-precipitation) by research laboratories and pharmaceutical professionals. Nowadays, techniques combining these two technologies are also frequently encountered. NSs can be presented to patients in liquid dosage forms, or post-production processes (freeze drying, spray drying, or spray freezing) can also be applied to transform the liquid state into the solid state for the preparation of different dosage forms such as powders, pellets, tablets, capsules, films, or gels. Thus, in the development of NS formulations, the components/amounts, preparation methods, process parameters/levels, administration routes, and dosage forms must be defined. Moreover, those factors that are the most effective for the intended use should be determined and optimized. This review discusses the effect of the formulation and process parameters on the properties of NSs and highlights the recent advances, novel strategies, and practical considerations relevant to the application of NSs to various administration routes.

Cyclosporine A is a calcineurin inhibitor and is usually used as an immunosuppressant medication. The main purpose of this study is to develop nanosuspension of polypeptide cyclosporine A by using the wet milling method for oral administration. Cell culture studies were also performed with human intestinal Caco-2 cell lines. Hydroxypropyl methylcellulose and sodium dodecyl sulfate were used as stabilizers in nanosuspension. In vitro characterization studies such as fourier transformed infrared analysis and morphological imaging with scanning electron microscopy have been carried out with obtained cyclosporine A nanosuspension. The particle size, particle size distribution, and zeta potential values ​​of the nanosuspension were measured approximately 400 nm, 0.4, -25 mV, respectively. The solubility of cyclosporine A was increased 4.5 times in nanosuspension compared to the coarse cyclosporine A powder. As a result of cytotoxicity studies conducted with different concentrations, it was decided to conduct permeability studies at a dose equivalent to 150 µg/mL cyclosporine A. Permeation studies have shown that the nanosuspension increases cyclosporine A transport by 5 and 1.5 times, respectively, compared to coarse powder and commercial product.

Objectives: This study aimed to develop nanosuspensions (NSs) of cyclosporine A (CycA) using a top-down technology [high-pressure homogenization-(HPH)] for oral administration. Materials and Methods: Formulas were prepared using different ratios of hydroxypropyl methylcellulose (HPMC) (1% and 0.5%) and sodium dodecyl sulfate (SDS) (1%) to improve the solubility of CycA. The HPH method was optimized by investigating the effects of critical formulation parameters (stabilizer ratio) and critical process parameters (number of homogenization cycles) on the particle size (PS), polydispersity index (PDI), and zeta potential (ZP) of NS using the Design of Experiment (DoE). After lyophilization, differential scanning calorimetry, X-ray diffraction, fourier-transform infrared spectroscopy, and morphological evaluation with scanning electron microscopy were performed. Stability studies were conducted at 4 degrees C and 25 degrees C storage conditions. The solubility of the optimum CycA NS was investigated by comparing it with a coarse CycA powder and a physical mixture (PM). In vitro dissolution studies were conducted in four media using United States Pharmacopeia apparatus I. Results: PS, PDI, and ZP values for the NS were approximately 250 nm, 0.6, and 35 mV, respectively. Under storage conditions, the CycA NS exhibited significant physical stability at both 4 degrees C and 25 degrees C for 9 months. The solubility of CycA was improved 1.9 and 1.4 times by NS in the presence of CycA powder and PM, respectively. CycA NS exhibited higher dissolution than CycA coarse powder in 0.1 N HCl, fasted simulated intestinal fluid, and fed simulated intestinal fluid. Conclusion: CycA NS was successfully developed using the DoE approach with the HPH method with HPMC:SDS combination in a 1:0.5 ratio, and the solubility and dissolution of CycA in the NS were improved.