## 3 Results and Discussion
### Drug (APR) Dissolution Study  
The dissolution study of apreptant (APR) was performed in all the above prepared and characterized APR/PEO and APR/PEO/clay nanocomposite samples. The dissolution profiles of pure APR and APR/PEO melt-mixed formulations without the addition of the clay are shown in Figure 15. APR reached a dissolution percentage of about 15% in the first 10 min, while after that time, the dissolution degree continued to increase with reduced rate and reached a value of approximately 40% at 60 min, without any other change thereafter. This was due to the crystalline structure of the drug, which reduced its solubility. All the APR/PEO formulations showed increased values in the first 10 min compared to that of the neat APR, with percentages reaching approximately 55-65%. After that time, the drug dissolution continued to increase, while the dissolution reached its maximum on the 30 min time mark, with values ranged between 75 and 90%. As can be seen, the drug release is directly dependent on the drug amount. The PEO/APR formulation with 5 wt % drug had the highest rate, that in fact decreased by increasing its amount in solid dispersion. Thus, the formulation with 20 wt % APR exhibits the lowest release from all formulations, which is ca. 75% after 60 min. It seems that PEO has succeeded to increase the initial release of the drug, leading to an immediate release profile followed by a sustained release till t = 60 min. The release rate decreased by increasing the drug amount, due to the different degree of crystallinity of the drug in the solid dispersions. In the formulation containing 5 wt % APR, the whole amount, as was found from XRD, was almost in an amorphous state. Thus, the release rate was the highest, since it is well known that amorphous drugs have up to 1000 times higher solubility than crystalline forms [41; 42]. As the drug amount increased in the formulations, a higher drug amount existed in a crystalline form, and thus the maximum release rate decreased gradually from 10 to 20 wt % APR. Figure 14: DSC curves of pure apreptant and different drug-loaded nanocomposites containing (**a**) 5 wt % (PEO_5 Aprep_5 CloisiteNa+, PEO_10 Aprep_5 CloisiteNa+ and PEO_20 Aprep_5 CloisiteNa+) and (**b**) 10 wt % clay (PEO_5 Aprep_10 CloisiteNa+, PEO_10 Aprep_10 CloisiteNa+ and PEO_20 Aprep_10 CloisiteNa+). The drug dissolution profiles of the APR/PEO formulations also containing 5 and 10 wt % clay are shown in Figure 15b,c, respectively. The incorporation of 5 wt % clay in the formulations seems to increase the drug release of net APR at values slightly higher compared to the formulations without clay; that is, 55-70% in the first 10 min. The main difference is that the presence of clay induces further dissolution enhancement of APR, which reached a release of approximately 98% after 60-120 min. This also happens in the other formulations containing 10 and 20 wt % APR, with maximum drug release of about 85 and 76%, respectively. Hence, the combination of 5 wt % clay and 5 wt % APR showed higher release rates compared to the neat drug as well as to the formulation without the clay. Based on the above results, it seems that the highly intercalated/exfoliated clay nanolayers present in the APR/PEO/5 wt % clay formulation (Figure XRD data in Figure 13) provide a high external surface for interaction with the drug and thus higher amorphisation. However, these effects depend also on the drug loading, even though in all formulations, the drug release is enhanced compared to the PEO/APR formulations, while 5-10 wt % APR loading appears to be the most appropriate range. For APR/PEO/clay formulations with 10 wt % clay (Figure 15c), different observations were made. It can be seen that even though enhanced release rates are recorded compared to the neat drug, they are slightly slower compared not only to the APR/PEO/5 wt % clay, but also to the APR/PEO formulations.