*Nano- and Microencapsulation - Techniques and Applications*

**3.2 General characteristics of the particles**

*DOI: http://dx.doi.org/10.5772/intechopen.93338*

*3.2.1 Shape*

*3.2.2 Particle size*

polydispersity [66].

*3.2.3 Drug entrapment efficiency*

*3.2.4 Physicochemical stability*

**107**

determining their pharmaceutical performance [61].

Regardless of the type of particle, the shape, the particle size, the drug entrapment, and loading, and the zeta potential are among the crucial properties

*Nanoprecipitation: Applications for Entrapping Active Molecules of Interest in Pharmaceutics*

Polymeric and hybrid particles prepared by using the nanoprecipitation technique exhibit spherical shape as it is revealed by techniques of microscopy, mainly scanning electron (SEM), transmission electron (TEM), atomic force (AFM), and field emission scanning microscopies (FESEM). To investigate the shape of lipid nanoparticles in most cases, the same techniques were used, and spherical shapes were also

reported. However, lipids might be melted during the sample examination destroying their native characteristics; consequently, controversial results could be obtained. For example, platelet shapes for SLN [62, 63] and structures with the liquid lipid located on the surface of the particles in the form of plates for NLC [64, 65] have been reported by using cryo-TEM and freeze-fracture TEM. Nevertheless, Dong et al. [24]

In general, the mean sizes, usually measured by dynamic light scattering, vary between less than 100 and 300 nm with PDI values below 0.4 (**Figure 3A** and **B**). It seems that polymeric nanocapsules and specially hybrid nanoparticles are the smallest; perhaps, any type of structural arrangement among the lipids and polymers could favor a better consolidation of the particle. With respect to lipid carriers, the platelet shapes as the lipids crystallize inside the particle could explain their high

Regarding the entrapment efficiency (**Figure 3C**), clear differences are identified among the carriers. Thus, polymeric nanocapsules entrap almost the totality of the active molecule in contrast with 40% attained by the SNL. As remarked by Westesen et al. [67], Pardeike et al. [68], and Weber et al. [69], when preparing SLN the solidification and the progressive crystallization of the lipid in more stable forms could lead the expulsion of the active substances whether during the particle formation or its consolidation. This results in eventual instabilities of the particle dispersions and, as evidenced in this case, low entrapment efficiency and loading of active molecules. On the other hand, as shown in **Figure 3D**, the best results of drug loading are reported for hybrid nanoparticles; active molecules could be located both in the polymeric core and the lipid layer of the particles maximizing their loading efficiency.

Stability of the particle dispersions has been investigated by using refrigerated storage [6, 8, 13, 15, 21], room temperature at 25°C [8, 13, 14, 21, 57], and accelerated conditions varying between 35 and 40°C [8, 9, 11, 20, 27]. Particle size, PDI, and zeta potential are usually followed during the storage time, and the physical integrity of the dispersions is observed for up to 6 months. This good stability is expected for these nanosystems considering their colloidal nature and the absolute

zeta potential values which are estimated varying between 15 and 40 mV.

report spherical shape from the analysis of SLN by using Cryo-FESEM.

#### **Figure 2.**

*Starting materials reported as used to prepare the organic and aqueous phases for obtaining polymer, lipid, and hybrid nanoparticles by the nanoprecipitation technique. Number of times reported for each starting material considering a total of 18, 11, and 13 research works for polymer, lipid, and hybrid particles, respectively [PLGA: poly(lactic-co-glycolic acid); PCL: polycaprolactone; PLA: poly(lactic acid); PEG: polyethylene glycol; HPMC: hydroxypropyl methylcellulose; DMSO: dimethyl sulfoxide; CAP: cellulose acetate phthalate; EtOH: ethanol; ACN: acetonitrile; MetOH: methanol; DMF: dimethylformamide; DCM: dichloromethane; THF: tetrahydrofuran; MEK: methyl ethyl ketone; H-b-pBG: hyaluronan poly(γ-benzyl-L-glutamate); PBS: phosphate-buffered saline; SDS: sodium dodecyl sulfate; GMS: glycerol monostearate; TPGS: tocopheryl polyethylene glycol succinate; PVA: polyvinyl alcohol; Tf-PEG-OA: transferrin-poly(ethylene glycol)-oleic acid; Tf: transferrin; HSA: human serum albumin; DSPE-PEG: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]].*

could form part of any of the phases according to their solubility. On the contrary, if a physical mixture of polymer and lipid is used, they are dissolved in the organic phase. Unlike polymeric and lipid particles, acetonitrile is reported as the most used organic solvent for preparing hybrid nanoparticles. Another interesting matter of the recipe to prepare hybrid nanoparticles is the versatile composition of the aqueous phase. In this sense, for example, lecithin and cholesterol can be dissolved in ethanol and then incorporated in the aqueous phase that could contain surfactants such as polysorbate and poloxamer. Likewise, dispersions of surfactants, proteins, or buffers were tested as the aqueous phase.
