Of binder which could lead to localized hts screening overwetting, and increase the chances of premature drug release. Therefore, increasing the binder concentration above 10% was not investigated. Previous reports show that the viscosity of the PVP solution is a function of the PVP concentration and inversely proportional to its temperature. Table 2 lists the measured viscosity as a function of temperature for both 1/9 PVP/H2O and 1/9 PVP/ EtOH. Due to the decreased viscosity of the binder solution with increased granulation temperature, the influence of granulation temperature on tablet properties and in vitro drug release was investigated.While the PVP/EtOH binder solution results in a lower viscosity, H2O was selected due to its more common use as a binder solvent. Table 3 compares the tablet properties, Carr Index, and Hausner Ratio results of the granulated material to that of the untreated COK 12. From a practical perspective, powders with a Carr Index 32 and Hausner Ratio 1.5 are characterized as very poor flowing powders. Regardless of granulation temperature, both materials displayed a substantial decrease in both Carr Index and Hausner Ratio values when compared to untreated COK 12. Based on these results, increasing the temperature from 50 C to 75C does not appear to further improve the flow. However, increasing the granulation temperature did increase the tablet hardness. The weaker 50 C granulated tablets are most likely a result of poor distribution of binder upon processing. Compared to the 75 C samples, this temperature gave rise to overly large particles stemming from localized over wetting. Along with microcrystalline cellulose, the disintegrant, croscarmellose sodium, has been shown to compensate for the release loss following compression of compacted OMS particles. Therefore, a 2.4 wt.% of AC was added as a physical mixture prior to compression. This resulted in a slight decrease in tablet thickness for both granulation temperature samples but had less effect on the tablet hardness.
For the 50 C granulated sample, a hardness value obtained with AC ranged from 0 to 4.4 kp. AC decreased the variability of the 75 C granulated samples which ranged from 5 to 6 kp compared to the granulate only of 4 7 kp. The sample granulated at 75 C was selected for further investigations. Due to insufficient sample, tapped density experiments necessary to calculate Carr Index AZD2171 and Hausner Ratio values were not measured with samples containing AC. It has been previously reported that applying pressure to OMS results in decreased pore volume and surface area which contributes to a reduced drug release rate. The changes in porosity following compression, as measured by N2 physisorption, are shown in Table 4. Compared to the non loaded COK 12, the lack of micropores detected and overall decrease in pore volume, surface area, and pore diameter is due to the successful loading of ITZ inside the micropores and along the mesopore walls. Following compression to 120 MPa, the overall pore volume and surface area of COK 12 decreased. Previous results show that only a slight decrease in pore diameter following compression is observed. These results are consistent with only a slight change of 0.1 nm in pore diameter. Following granulation, the decrease in pore dia.