Effect of Process Parameters on Formation and Aggregation of Nanoparticles Prepared with a Shirasu Porous Glass Membrane

Abstract

The objectives of this study were to prepare itraconazole (ITZ) nanoparticles using a Shirasu porous glass (SPG) membrane and to characterize the effects of diverse preparation parameters on the physical stability of nanoparticles. SPG membrane technology was used for the antisolvent precipitation method. The preparation of nanoparticles was carried out over a wide range of continuous-phase factors (type of surfactant, surfactant concentration), dispersed-phase factors (solvent type, solvent volume used to dissolve ITZ), and technical factors (pressure, membrane pore size, stirring speed in the continuous phase, temperature). Improved physical stability of nanoparticles was observed when surfactant with a lower molecular weight and higher hydrophilic segment ratio was used. The water miscibility of the solvent also had an effect on the physical stability. N,N-Dimethylacetamide contributed to creating a well-rounded shape and narrow size distribution due to high miscibility. Concentration of the surfactant and solvent volume used for dissolving ITZ were related to instability of nanoparticles, resulting from depletion attraction and Ostwald ripening. In addition to these factors, technical factors changed the environment surrounding ITZ nanoparticles, such as the physicochemical equilibrium between surfactant and ITZ nanoparticles. Therefore, the appropriate continuous-phase factors, dispersed-phase factors, and technical factors should be maintained for stabilizing ITZ nanoparticles.Key words Shirasu porous glass membrane; antisolvent precipitation; nanoparticle; itraconazole; physical stability Oral administration of poorly water-soluble drugs often leads to many problems in drug research and development. The aqueous solubility of a drug is an important factor for its dissolution rate. Poorly soluble compounds tend to be eliminated from the gastrointestinal (GI) tract before they have had opportunity to be absorbed into the circulation, and the low dissolution rate arising from low solubility results in low bioavailability. In such cases, dose escalation often causes topical toxicity in the GI tract and reduces patient compliance, which would be required for reaching therapeutic concentrations in the blood. 1)There have been many attempts to increase bioavailability and dissolution rate of poorly water-soluble drugs. These include solid dispersions composed of solid state microfines or molecular dispersions, water-soluble cyclodextrin complexes and self-emulsifying drug delivery systems using diverse surfactants.1,2) The principle limitation of all these approaches is that the drug needs to have certain physicochemical properties. For example, sufficient solubility in oils or surfactants is needed for self-emulsifying drug delivery systems and the proper molecular size is essential for synthesizing a complex with cyclodextrin. In addition, the use of solubilizing excipients in drug solubilization is limited because of their toxicity or volume of formulation. Because of these limitations, there are the relativel...

Encapsulation and Controlled Release of Rapamycin from Polycaprolactone Nanoparticles Prepared by Membrane Micromixing Combined with Antisolvent Precipitation

“…In this series of experiments, blank PCL NPs were prepared using two different organic solvents, Figure 2. The same trend was observed for itraconazole and ZnO NPs prepared via SPG membrane, 42,43 and liposomes and micelles produced using nickel membrane. 27,44,45 .…”

“…The Z -average mean decreased with increasing aqueous-to-organic volumetric ratio, as shown in Figure . The same trend was observed for itraconazole and ZnO NPs prepared via SPG membrane, , and liposomes and micelles produced using nickel membrane. ,, The size of NPs formed by antisolvent precipitation is a result of the relative rates of nucleation, particle growth, and agglomeration. The faster removal of solvent at higher V aq / V or values led to higher supersaturation levels, which promoted nucleation over particle growth and resulted in smaller NPs.…”

Oral nanoemulsions of candesartan cilexetil: formulation, characterization and in vitro drug release studies

“…Another point to be added that further potentiate the NE stability is the polymeric and bulky flexible structure of poloxamer which can stabilize the nanosystem by creating spatial exclusion, cover the surface of nanodroplets efficiently and avoid the formation of van der Waals forces between the nanodroplets (Pratiwi et al 2016;Seo et al 2015).…”

Single synchronous delivery of FK506-loaded polymeric microspheres with pancreatic islets for the successful treatment of streptozocin-induced diabetes in mice

“…Then, the solution was filtered, diluted appropriately, and quantified by using HPLC method, as described previously (Pathak et al., 2016a ). Encapsulation efficiency (EE) was calculated using the following formula (Kondo et al., 2015 ; Seo et al., 2015 ; Zhao et al., 2015 ): …”