Freeze-drying of nanoparticles

The poor long-term stability of nanoparticles in aqueous medium results in serious drawbacks for pharmaceutical applications. Water should thus be removed from the system in order to prevent the aggregation of nanoparticles, the destruction of polymer constituting the nanoparticles, and the escape of drug entrapped in the nanoparticles, thus enhancing the physical and chemical stability of these colloidal systems 

In general, the great majority of the products undergoing a freeze-drying process are processed from aqueous solutions. Nevertheless, both organic or water/organic 

This result can be accomplished in the case where TEA is used as solvent in the manufacturing process, as recently discussed by Zelenkova et al. [73]. 

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Abdelwahed, W, Degobert, G., Stainmesse, S., and Fessi, H., Freeze-drying of nanoparticles Formulation, process and storage considerations, Adv. Drug Deliv. Rev., 2006,58,1688-1713. 

Fouarge and Dewulf [3.45] reported about the freeze drying of poly (isohexylcyanocrylat) nanoparticles, which were loaded with dehydroemetine (DHE). The load of absorbed DHE was uniform and reproducible. The stability remained good during 24 months, and the acute toxicity of DHE was reduced by combination with nanoparticles, as was the radical concentration. 

Schwarz C. and Mehnert W, Freeze-drying of drug-free and drug-loaded solid lipid nanoparticles, Int. J. Pharm., 157, 171, 1997. 

The use of crystalline nanoparticles of cellulose (CNP) allows for paving a new path for the development of nanocosmetics. The CNP for cosmetics application can be produced by hydrolysis of pure cotton cellulose with mineral acids as was described in Section 9.3.1. The paste of CNP for cosmetic application was obtained by evaporation of dilute aqueous dispersion. The powder of CNP was prepared by freeze-drying of the aqueous dispersion. Testing has shown that the obtained powder of CNP meets requirements of the US pharmacopeia 23/NF 18 for inactive medical excipients (Table 9.13). 

T. Zelenkova, D. Fissore, D.L. Marchisio, and A.A. Barresi, Size control in production and freeze-drying of poly-e-caprolactone nanoparticles. Journal of Pharmaceutical Sciences, 103 (6), 1839-1850, 2014. 

Anhorn MG, Mahler HC, Langer K. Freeze drying of human serum albumin (HSA) nanoparticles with different excipients. Int J Pharm. 363 (1-2) 162-169,2008. 

Fattale et al. [3.46] compared negatively charged liposomes with nanoparticles from poly- (isohexyl-cyanoacrylate), which of both were loaded with ampicillin. Both carriers were of approximately the same size 200 nm but the nanoparticles could be loaded with approx, twenty times more ampicilin. After freeze drying and storage at-4 °C, no ampicillin leaked from the nanoparticles, while it migrated quickly from the liposomes. 

The determination of the molecular weight of nanoparticles is performed by gel permeation chromatography (GPC). The experimental setup consists of a high performance liquid chromatography system with a size exclusion column and a refractive index detector. The nanoparticles are usually freeze-dried and dissolved in tetrahydrofuran for analysis on the system. Poly(styrene) or poly(methylmethacrylate) standards are used to calibrate the column, to enable the determination of number average molecular weight (Mn), as in... 

Particle size is one of the most important characterization parameters for sohd hpid nanoparticle dispersions, and parameters relahng to particle size are consequently reported in all stndies on these systems. Particle size determinations are predominantly performed to conhrm that the desired colloidal size range has been obtained dnring preparation and that it is retained upon storage or further processing (e.g., during freeze drying or sterilization). 

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