## 5 Additives in Melt Electrospinning
### Pharmaceutical Additives  
In recent years, there has been an increasing attention for melt electrospinning in the pharmaceutical field as it overcomes certain disadvantages that solution electrospun fibers and other drug delivery systems present, some of which have been previously mentioned in this review. Other hindrances related to solution electrospun fibers are the low loading attained when poor soluble drugs are involved [87]; typical burst release; and low drug in the thin fibers [88; 89]. However, it is important to mention that, despite the growing interest in the technique, it is still at the dawning/development step and that most papers being published in this field use solution electrospinning [90]. For this reason, melt electrospinning is not a panacea--or at least, not yet--as there are several aspects that need to be improved. Currently, studies on melt electrospun fibers able to be used as drug nanocarriers are being developed (see Table 2) [91]. Nevertheless, most biological molecules are thermosensitive, which in some cases make their use in melt electrospinning impossible [92; 93]. Logically, the incorporation of plasticizers can be useful in some cases as they decrease the process temperature [94; 95] by lowering intermolecular forces among polymer chains [96]. Three Food and Drug Administration (FDA) inactive pharmaceutical ingredients (triacetin, Tween 80, and PEG 1500) have been approved and considered for melt electrospinning. [PERSON] [95] has successfully melt electrospun EUR fibers loaded with carvedilol. A good compatibility was observed between EUR  
Figure 7: Effect of salt additives on the melt-electrospun PCL fibers. The micrographs of the nonwoven materials is: (**a**) without additive, (**b,c**) with an NaCl additive of 8 wt.% and 25 wt.%, respectively. (**d**) Average diameter of the PCL fiber as a function of the additive content. Copyright 2019 MDPI [80]. amorphous methacrylate terpolymer matrix, and carvedilolol [87], a highly lipophilic and thermosensitive beta-blocker drug [97]. Results showed that the application of plasticizers reduced the polymer melting temperature and prevented the degradation of the drug. Furthermore, and the dissolution and release of carvedilol from the fibers was ultrafast, especially in comparison with the pure crystalline drug. [PERSON] et al. [98] studied also the effect of water as a plasticizer in the incorporation of indomethacin, another poorly water soluble drug, using the copolymer Soluplus(r) as drug carrier. Results demonstrated the plasticizing effect of water, the fast drug release and that both polymer and drug remained stable during the spinning process. The drug dissolution and release from fiber mats do not only depend on the fiber composition [99], but also on the geometry of the final product (thin film, cylindrical sample, etc) [100; 101; 102], the fiber diameter and porosity [103; 104], the way as the drug was loaded [101; 105], and the hydrophilic nature of the matrix [106; 107]. In many of the recent studies where drug-loaded polymer fibers were prepared by melt electrospinning, PCL has been selected as the drug carrier due to its excellent properties. Thus, PCL is compatible with other polymers [108], its degradation products can be metabolized by the citric acid cycle [109], it is biocompatible according to both in vitro and in vivo assays [110; 111]. Probably, the main limitation of PCL for biological applications concerns