Meter from 7.5 to 7.3 nm is due to partial Everolimus RAD001 pore blockage of PVP. As with untreated COK 12, an overall decrease in volume and surface area is observed following compression. However, the decrease in pore diameter from 7.3 to 6.8 nm is most likely due to further spreading of PVP across the COK 12 particles upon compression and, therefore, additional pore blockage. ITZ release before and after compression of the 75 C granulated sample described in Table 3 with comparison with crystalline ITZ. Following compression to 120 MPa, results show a slight decrease in release up to 30 min. The addition of 2.4 wt.% AC was successful in achieving full release recovery following compression. It has been previously shown that full release recovery was achieved with a physical mixture containing 28.5% COK 12. Here, wet granulation was able to achieve this with the high COK 12 concentration of 73.2%. A morphological comparison of granulates prepared from the optimized parameters to the untreated COK 12 is shown in Fig. 5. COK 12 has been described as silica platelets with short channels crossing a uniform plate thickness of ca. 250 nm. Compared to COK 12, wet granulation displays an overall increase in particle size and smoothing of the particle surface by filling the platelet voids with PVP. This observation correlates well with the improved powder flow shown in Table 3. To investigate whether further release occurred during storage, a 20 wt.% ITZ loaded COK 12 sample was treated with either pure milli Q H2O or EtOH at a 50 lL/min rate for 30 min. Samples were then stored in conditions of 25 C/0%RH, 60 C/0%RH, and 25 C/69%RH. As determined by the enthalpy of fusion, no additional drug release was observed for both H2O and EtOH treated samples for each timepoint. compound dependent. Fig. 6 displays the thermograms of pure COK 12 and loaded material wherein no thermal event is observed, thus indicating successful drug loading into the pores. The target PVP concentration for all compound comparison experiments was 25%.
ITZ and NAP were granulated at 75 C. Due to the lower Tm of IBU and FNF, granulation temperature was reduced to 65 C. The MDSC results following granulation with 10% PVP binder solution with either H2O or EtOH are shown in Fig. 7. Regardless of binder solution used, no thermal event was observed for NAP, IBU, or FNF. Using NAP loaded COK 12, the influence of solubility on premature drug release was investigated. The pH of 1/9 PVP/H2O was 3.6. NAP is a weak acid with a pKa of 4.2 and therefore is mainly in the unionized form at pH 3.6. Using sodium hydroxide, two binder solutions of 1/9 PVP/H2O were prepared with the pH adjusted to Ostarine either 6 or 8. Following the same granulation conditions as in the original experiment, no thermal event was observed. Regardless of binder solution, an endothermal event corresponding to the Tm of ITZ was observed following granulation during the initial heating of 20 C/min. It has been previously reported that higher drug loadings result in higher percentage release rate due to the covering of less energetically favorable sites. Therefore, the effect of initial drug loading on premature drug release was investigated. ITZ granulation experiment conditions were repeated with a varying drug load of either 4.6 0.0, 9.0 0.