Nanosuspensions stability

Existing formulations possessing side effects due to the excipients used (e.g., Cremophor EL) could be replaced by nanosuspensions stabilized by well-tolerated excipients (e.g., lecithin, poloxamer 188). 

Van Eerdenbrugh B, Van den Mooter G, Augustijns P (2008) Top-down production of drag nanocrystals nanosuspension stabilization, miniaturization and transfmniation into solid... 

The principles of particle stabilization are even more critical to the stabilization of very small solid particles, less than one micron in diameter (e.g., nanosuspensions), which have much greater surface area. The Ostwald-Freundlich equation,... 

Nanosuspensions Drug nanocrystals dispersing in aqueous media commonly stabilized by surfactants Suitable for insoluble drugs to obtain good bioavailability and targeting 19... 

Nanosuspensions Pure drugs and stabilizers (including surfactants or polymers) Precipitation, wet milling, homogenization 19,60,61... 

Recently,with respect to the importance of particle size distribution in terms of particle characterization and product physical stability testing, there has been interest in newer light-scattering methods for particle detection called photon correlation spectroscopy (PCS). PCS methods can be applied to both micro-and nanosuspensions. 

The key to long-term physical stability of aqueous nanosuspensions is the selection of a suitable water-soluble surfactant or polymer as an external particle stabilizer to prevent particle growth. Several potential stabilizers are lecithin, phospholipids, poloxamers, and polysorbates. 

The physical stability of nanosuspensions may be monitored with the use of electron microscopic analysis. 

A schematic representation of the variation of G jx> Gg] surface-surface separation distance h is shown in Figure 13.5. G jj, increases very sharply with decrease of h, when h < 25. while G j increases very sharply with decrease of h, when h<5. Gj versus h shows a minimum, G, at separation distances comparable to 25, and when h < 25, Gj shows a rapid increase with decrease in h. The depth of the minimum depends on the Hamaker constant A, the particle radius R, and the adsorbed layer thickness 5. increases with increase of A and R. At given values of A and R, G increases with a decrease in 5 (i.e., with a decrease in the molecular weight, M, of the stabiliser). This is illustrated in Figure 13.6, which shows the energy-distance curves as a function of 5/R, and where the larger is the value of 5/R the smaller is the value of G j, . In this case, the system may approach thermodynamic stability, as is the case with nanosuspensions. 

CDC are defined only by their size (most scientists agree on sizes below 1 pm others set 0.5 pm as the upper limit). CDC are very heterogeneous in all other aspects (e.g., thermodynamic stability, chemical composition, and the physical state, including solid, liquid, or liquid-crystalline dispersions) [ 1 ]. The most prominent examples are nanoparticles, nanoemulsions, nanocapsules, liposomes, nanosuspensions, (mixed) micelles, microemulsions, and cubosomes. Some CDC have reached the commercial market. Probably the best known example is the microemulsion preconcentrate of cyclosporine (Sandimmun-Neoral), which minimized the high variability of pharmacokinetics of the Sandimmun formulation. In addition, intravenous injectable CDC have been on the commercial market for many years. Examples include nanoemulsions of etomidate (Etomidat-Lipuro) and diazepam (Diazepam-Lipuro) [2-4], mixed micelles (Valium-MM, Konakion), and liposomes (AmBisome) [5]. 

Use as a template to fabricate nanoparticulate systems The inherent thermodynamic stability, large interfacial area and small droplet size of the microemulsions enable them to act as a template for facile synthesis of pharmaceutical nanoparticulates systems such as solid lipid nanoparticles [11] and nanosuspensions [12]. Additionally, microemulsions represent nanoreactors which can be tailored to fabricate pharmaceutical nanomaterials. 

Nanosuspensions consist of the pure poorly water-soluble drug without any matrix material suspended in dispersion. It is sub-micron colloidal dispersion of pure particles of drug stabilized by surfactants. By formulating nanosuspensions, problems associated with the delivery of poorly water-soluble drugs and poorly water-soluble and lipid-soluble drugs can be solved. Nanosuspensions differ from nanoparticles, " which are polymeric colloidal carriers of drugs (nanospheres and nanocapsules), and from solid-lipid nanoparticles, which are lipidic carriers of drug. 

Apart from the already established formulations, researchers are trying to develop novel oil-based formulations to combat the poor solubility and bioavailablity of NCE. Shevachman et al. developed novel U-type microemulsions to improve the percutaneous permeability of diclofenac. Shah et al.2 2 used microwave heating for the preparation of solid lipid nanoparticles by microemulsion techniques, which resulted in improved particle characteristics. Ki et al. reported sustained-release liquid crystal of injectable leuprolide using sorbitan monooleate. Recently, various novel oil-based drug delivery technologies are reported, which includes tocol emulsions, solid lipid nanopar-ticles, nanosuspensions, Upid microbubbles, sterically stabilized phospholipid micelles, and environmentally responsive drug delivery systems for parenteral administration.25 259... 

VI. Physical Long-Term Stability of Aqueous Nanosuspensions 397... 

To. summarize For autoclaving, nanosuspensioms need preferentially to he stabilized by charged emulsifiers such as lecithin (Phospholipon). Similar to fat emulsions for parenteral nutrition, which are also stabilized by iecUhin. nanosuspensions can withstand the sterilization procedure. 

---