*4.1.5 Wet granulation*

*Current and Future Aspects of Nanomedicine*

*4.1.2 Spray drying*

*4.1.3 Extrusion/spheronization*

*4.1.4 Microencapsulation*

surface roughness as well as the extrusion force [88].

During the formulation of s-SEDDS by adsorption technique, careful consideration should be given to the possible interactions between the solid carrier and the drug or other excipients in liquid SEDDS which could result in delayed or incomplete release of loaded drug [83]. Additionally, the particle size, specific surface area, tortuosity of pores as well as type and liquid SEDDS: carrier ratio should be considered [75].

Spray drying is also a promising technique for transforming liquid SEDDS to s-SEDDS using different carriers (i.e., hydrophobic or hydrophilic carriers) which preserve the self-emulsifying properties of the formulation. It is a simple and economical technique which involves mixing of lipids, surfactants, drug and solid carriers followed by solubilization and spray drying. The solubilized mixture is atomized into a spray of fine droplets that are introduced into a drying chamber where the volatile phase evaporates forming dry particles under controlled conditions of temperature and airflow [74]. The type of carrier can affect the rate of release and thus the oral bioavailability of loaded drug by affecting the droplet size of the nano or microemulsion formed after reconstitution [84]. Also, careful consideration should be given to the atomizer, the airflow pattern, the temperature and the design of the drying chamber which should be selected according to the powder specifications. Low yield is a disadvantage of solidification by spray drying technique which could be attributed to the removal of non-encapsulated drug with the exhausted air [85].

Extrusion/spheronization is the most explored technique for the production of uniformly sized self-emulsifying pellets [75]. Extrusion is a procedure of converting a raw material with plastic properties into a spaghetti-shaped agglomerate having uniform density. Extrusion is followed by spheronization where the extrudate is broken into spherical pellets (spheroids) of uniform size [86]. The produced pellets have good flowability and low friability. Before pellet production, the wet mass is composed of liquid SEDDS, lactose, microcrystalline cellulose (MCC) and water. A disintegrating agent could be added to enhance drug release [87]. MCC acts as adsorbent for the liquid SEDDS to ease pellet formation and avoid problems such as poor flow properties, pellet agglomeration and low hardness. Larger amount of liquid SEDDS can be loaded into the pellets when a greater quantity of MCC on the account of lower amount of lactose is employed in the formulation. The ratio of lactose: MCC and liquid SEDDS: water affects the pellets' disintegration time and

Co-extrusion technique is a promising strategy for microencapsulation of liquid SEDDS into polymeric matrices. This technique employs a vibrating nozzle device equipped with a concentric nozzle. The formed microcapsules are then hardened by ionotropic gelation. Ionotropic gelation is based on the gel formation ability of polysaccharides (e.g., pectin, alginate, carrageenan, and gellan) in the presence of multivalent ions (e.g., Ca+2) [89]. Alginate and pectin are the most intensively investigated natural ionic polysaccharides for formation of microcapsule shell. However, Ca-alginate microcapsules clog the nozzle during the microencapsulation process. On the other hand, pectin microcapsules lack sufficient hardness. Thus, microcapsules composed of an alginate-pectin matrix could be more acceptable than those composed solely of one polymer. Various hydrophilic filling agents

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Different carriers (e.g., Aerosil® 200) were employed to prepare the self-emulsifying granules where the liquid SEDDS acts as a binder. However, granulation with SEDDS produces a broader size distribution and difficult to control aggregation compared with granulation procedure where water is employed as granulating agent [91].
