Formulation and characterization of biocompatible and stable I.V. itraconazole nanosuspensions stabilized by a new stabilizer polyethylene glycol-poly(β-Benzyl- l -aspartate) (PEG-PBLA)

Abstract

Formulation and characterization of biocompatible and stable I.V.itraconazole nanosuspensions stabilized by a new stabilizer polyethylene glycolpoly(␤-Benzyl-L-aspartate) (PEG-PBLA).International Journal of Pharmaceutics http://dx.doi.org/10. 1016/j.ijpharm.2017.08.082 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractAmphiphilic block copolymers, PEG-PBLA with different molecular weights, were synthesized and used as new stabilizers for Itraconazole nannosuspensions (ITZ-PBLA-Nanos). ITZ-PBLA-Nanos were prepared by the microprecipitation-high pressure homogenization method, and the particle size and zeta potential were measured using a ZetaSizer Nano-ZS90. Morphology and crystallinity were studied using TEM, DSC and powder X-ray. The effect of the PEG-to-PBLA ratio, and the drug-to-stabilizer ratio were investigated to obtain the optimal formulation. It was found that the optimal length of hydrophobic block was 25 BLA-NCA molecules and the optimal ratio of drug/stabilizer was 1:1, where the resulted average particle size of ITZ-PBLA-Nanos was 262.1±7.13 nm with a PDI value of 0.163±0.011. The images of TEM suggest that ITZ-PBLA-Nanos were rectangular in shape. ITZ existed as crystals in the nanoparticles as suggested by the DSC and XRD results. Compared with the crude drug suspensions, the dissolution rate of ITZ nanocrystals, was significantly increased and was similar to Sporanox ® injection. The ITZ-PBLA-Nanos also demonstrated better dilution stability and storage stability compared with ITZ-F68-Nanos. The particle size of ITZ-PBLA-Nanos did not change significantly after incubated in rat plasma for 24 h which is a good attribute for I.V. administration. Acute toxicity tests showed that ITZ-PBLA-Nanos has the highest LD50 compared with ITZ-F68-Nanos and Sporanox ® injection. ITZ-PBLA-Nanos also showed stronger inhibiting effect on the growth of Candida albicans compared with Sporanox ® injection. Therefore, PEG-PBLA has a promising potential as a biocompatible stabilizer for ITZ nanosuspensions and potentially for other nanosuspensions as well.

Enhanced oral bioavailability of magnolol via mixed micelles and nanosuspensions based on Soluplus ® -Poloxamer 188

“…Hydrophobic micelles were likely to exhibit a higher solubilization capacity than hydrophilic forms do, and the increased hydrophobicity of the MMs cores enhanced their stability following dilution. Furthermore, in MNs, Soluplus ® and Poloxamer 188 likely adsorbed onto the surface of the nanoparticles more strongly than the other stabilizers did, thereby protecting the drug against dilution (Deng et al., 2010 ; Zong et al., 2017 ). However, when a large amount of liquid dilution occurs, the concentration of stabilizer in MNs decreases, and the stabilizer cannot maintain adsorption on the surface of magnolol.…”

Molecularly Imprinting Polymers (MIP) Based on Nitrogen Doped Carbon Dots and MIL-101(Fe) for Doxorubicin Hydrochloride Delivery

“…Therefore, many researchers are endeavoring to research and develop drug delivery systems (DDS) for DOX. For this purpose, polymer conjugates [ 6 , 7 ], metal-organic frameworks [ 8 , 9 , 10 ], and polymeric micelles [ 11 ] have been applied as carriers for DOX delivery.…”

Study on Formulation, in vivo Exposure, and Passive Targeting of Intravenous Itraconazole Nanosuspensions

“…Nanosuspensions have been used to deliver the poorly soluble ITZ using various stabilizers, such as poloxamer 407 (Matteucci et al., 2006), Hydroxypropyl methyl cellulose (HPMC) (Matteucci et al., 2007; Matteucci et al., 2009), Polyvinyl alcohol and glycyrrhizinic acid (Fernández-Ronco et al., 2015), poloxamer 188 and sodium deoxycholate (Rabinow et al., 2007), tween 80 (Wlaz et al., 2015), the hybrid of HPMC and sodium dodecylbenzene sulfonate (SDS) (Azad et al., 2016), and tween 20 (Foglio Bonda et al., 2016). As many of these formulations have various limitations such as large particle size, poor stability, or toxicity for intravenous administration (Decuzzi et al., 2010; Pu et al., 2012), a new stabilizer, polyethylene glycol-poly(Benzyl aspartic acid ester) (PEG-PBLA), has been employed to stabilize ITZ nanoparticles (Zong et al., 2017). The PEG-PBLA-stabilized ITZ nanosuspensions (ITZ-Nanos) were fabricated by a combination of microprecipitation and high-pressure homogenization (mPHPH) method (Zong et al., 2017).…”

“…As many of these formulations have various limitations such as large particle size, poor stability, or toxicity for intravenous administration (Decuzzi et al., 2010; Pu et al., 2012), a new stabilizer, polyethylene glycol-poly(Benzyl aspartic acid ester) (PEG-PBLA), has been employed to stabilize ITZ nanoparticles (Zong et al., 2017). The PEG-PBLA-stabilized ITZ nanosuspensions (ITZ-Nanos) were fabricated by a combination of microprecipitation and high-pressure homogenization (mPHPH) method (Zong et al., 2017). The ITZ-Nanos demonstrated good stability and biocompatibility in comparison with poloxamer 188-stabilized nanosuspensions.…”