## 1 Introduction  
Zinc (Zn) is one of dietary micronutrients and it is second highest trace element in the body [1]. Over 95% of Zn is located in the cells, but its dominant storage site is absent in the body [1]. There are three physiological roles of Zn: catalytic, structural, and regulatory activities [1]. Zn is known to be primarily absorbed in the duodenum and jejunum via transporters [2]. Its absorption may be reduced by phytate, fiber, and iron, but improved by citric acid [3; 4]. Homeostasis of Zn concentrations in cell and plasma is maintained by the regulation of absorption, excretion, and retention [1; 5]. Deficiency of Zn may result in anorexia, dysgseusia, dysosmia, skin rash, infection, alopecia, growth failure, and impaired wound healing [1]. Therefore, adequate supplementation of Zn is very important to maintain normal physiological conditions. Several oral formulations (i.e., tablet and capsule) of ZnSO4 are already commercially available. Nevertheless, there has been a little progress in the development of pharmaceutical dosage forms of ZnSO4. Especially, there are a few reports regarding the development of nanoformulations of ZnSO4 for oral administration. The barriers in the absorption process of ZnSO4 can be overcome by the introduction of nano-sized formulation.  
Inorganic crystals, metals, and salts may be classified into lyophobic materials. Their affinity to solvents (i.e., water) is very low; thus, thermodynamic work is necessary for dispersing those materials in solvents. Diverse preparation methods have been developed for the development of nano-sized particles of metal [6]. HME is a continuous manufacturing process that can be easily scaled up [7]. Materials can be thrown into the extruder, moved towards the die and homogeneously blended by rotating screws, and extruded from the die (or an orifice) [8; 9; 10; 11]. During the HME process, the temperature of barrels is designed above the glass transition temperature (T\({}_{\mathrm{g}}\)) and sometimes over the melting temperature (T\({}_{\mathrm{m}}\)) of polymeric substances, and the drug can be molecularly dispersed in the polymer matrix [9; 12; 13].  
Soluplus (SP) was used as the main polymer matrix for HME processing in this investigation. SP is a grafted polymer composed of polyethylene glycol, polyvinylcaprolactone, and polyvinylacetate, so it has an amphiphilic characteristic. It has white to yellowish granules, and its molecular weight is ~118,000 g/mol. It can be used as a binder, a solubilizer, a film-former, and a stabilizer. Of note, it has been widely used as a main matrix for the production of HME formulations due to its thermodynamic properties [14; 15]. Conclusively, the use of SP in HME processing can improve solubility and the bioavailability of poorly water-soluble drugs [9; 14; 16; 17]. So far, the HME technique has been used principally to make solid dispersions of organic molecules, which have low molecular weight and poor water solubility, with appropriate polymers (i.e., cellulose derivatives, poly (ethylene-co-vinyl acetate), polyethylene glycol, polyvinylpyrrolidone, and SP) [9; 14; 16; 18]. Herein, ZnSO\({}_{4}\)/SP nanocomposites (NCs) were fabricated by HME processing, and their physicochemical and biosafe properties were investigated.