Assessment of the relative performance of a confined impinging jets mixer and a multi-inlet vortex mixer for curcumin nanoparticle production

Impact of molecular rearrangement of amphiphilic stabilizers on physical stability of itraconazole nanoparticles prepared by flash nanoprecipitation

“…As a means of tackling the process controllability issue, flash nanoprecipitation (FNP), a controlled antisolvent process, has been subsequently developed (Johnson and Prud'homme, 2003). Process control is mainly achieved by using a specially designed mixer such as confined impinging jet (CIJ) mixer and multi-inlet vortex mixer (MIVM) (Chow et al, 2014;Liu et al, 2008a), which provide high-efficiency mixing of all components present. Employing various amphiphilic co-block polymers as stabilizers, the technology has proven effective for consistent production of nanoparticles with a defined mean particle size (< 200nm) and a narrow particle size range (Chow et al, 2015;Zhu et al, 2007).…”

Development of highly stabilized curcumin nanoparticles by flash nanoprecipitation and lyophilization

“…Two stabiliz-129 ers, an amphiphilic diblock copolymer (i.e., PEG-PLA 2-8 k) plus a 130 co-stabilizer (i.e., PVP), were found necessary to maintain the sta-131 bility of the CUR nanoparticles during subsequent processing treat-132 ments (i.e., dialysis and freeze drying). Further work comparing the 133 relative performance of a CIJ-D-M and an MIVM also indicated that 134 while good particle size control could be achieved with either 135 mixer, the stability of the preparation in the presence of copolymer 136 stabilizer alone could not last for more than a few hours even with 137 some process optimization [22]. It should be reiterated that our 138 choice of CUR in this previous work was guided by it having a 139 log P value ($3) typical of most drugs and its wide array of proven 140 pharmacological activities (e.g., anti-oxidative, anti-inflammatory, 141 cholesterol-lowering, anti-amyloid, and anti-cancer activities), 142 which may be beneficial to the treatment of Alzheimer's disease 143 and cancers [23,24].…”

“…Apparently, the extremely high 148 lipophilicity or poor water solubility of such compounds favors 149 their tight binding to the hydrophobic cores of the particles, which 150 accounts for their superior nanoparticle stability. For drugs in the 151 typical log P range of 3-5, such binding in the nanoparticle cores 152 is expected to be weaker, which possibly explains why our CUR 153 nanoparticles are relatively unstable when formulated with the 154 copolymer stabilizer alone [22]. 155 As an alternative formulation approach to generating stable 156 curcumin nanoparticles by FNP using the CIJ-D-M, Margulis and 157 co-workers employed a coarse oil-in-water emulsion instead of a 158 simple solution of curcumin to co-mix with water in the initial 159 mixing step inside the mixer [26].…”

“…478 Interestingly, exclusion of the particle size data for the control 479 sample (i.e., without any stabilizer) from the linear correlation [32]. Such a discrepancy could be explained by the difference in [20], and has proven effective for achieving homogenous mixing of 493 all solute components involved prior to particle nucleation in the 494 nanoparticle production of a good number of hydrophobic com-495 pounds or drugs, including CUR, in previous studies [22,33]. 496 However, it should be noted that the condition of homogenous 497 stream mixing is not always guaranteed with any CIJ mixer, as this 498 would depend on the kinetics of competition between stream mix-499 ing and solute nucleation, which in turn is governed by the mixer 500 design as well as the characteristics of the mixing system involved 501 (e.g., flow rate, solute composition/concentration and related prop-502 erties) [34].…”

“…A volatile, partially out using the CIJ-D-M) afforded visible precipitates [26]. 185 In the present study, rather than modifying the formulation and 186 method of preparation as Margulis et al did [26] to resolve the sta-187 bility issue with nanoparticle production by FNP, we propose to 188 include an auxiliary stabilizer (co-stabilizer) in the formulation 189 to offer the nanoparticles additional protection once they are properties with different mixing systems [18]: The intensity-weighted particle size, polydispersity index (PI) 252 and zeta potential of samples were measured by a Delsa™ Nano 253 C particle size analyzer (Beckman Coulter, Miami, FL, USA) as 254 described previously [22]. In addition to PI, another parameter, 255 span, was used to quantify particle size distribution.…”