Ther through mobile liquid bridges, held by capillary Idarubicin Idamycin and viscous forces until more permanent bonds are formed following drying or sintering. This increased particle size, improves flowability and compactibility which leads to improvements in dose uniformity and tablet properties. The three main processes in determining wet granulation behavior are wetting, coalescence, and nucleation, consolidation and growth, and breakage and attrition. These parameters need to be sufficiently understood prior to any theoretical predictions can be made on formulation properties, equipment, or operating conditions. The lack of predictive behavior of the granulation process has complicated the development of suitable models, and consequently, the granulation process is often considered to require a trial and error approach. A primary concern during wet granulation of OMS was to achieve a balance of maintaining the OMS as dry as possible to avoid premature drug extraction yet wetting the material enough to form liquid bridges necessary for agglomeration. While H2O is often the solvent of choice, EtOH was also investigated due to its lower boiling point of 78 C. 3.1. Assessments with itraconazole loaded COK 12 The influence of binder addition rate on ITZ release was determined by adding 20, 50, or 100 ll of 5% binder solution in H2O to drug loaded COK 12 every minute until a final concentration of 14 wt.% PVP was achieved. As seen in Fig. 1, these samples showed no thermal event besides the evaporation of adsorbed H2O and indicate that ITZ was not extracted from the pores during the granulation step. Their in vitro release behavior before and after 120 MPa compression is shown in Fig. 2. Prior to compression, no significant difference is observed between samples. Following compression, the release rate increases with decreasing binder addition rate.
The chances of localized overwetting decrease by reducing the binder addition rate which results in a more homogeneous and thin layer distribution of the binder liquid. The 100 ll/ min addition rate resulted in excessively parthenolide large agglomerates due to localized over wetting and inhomogeneous distribution of PVP. These results are consistent with previous findings in which Holm reported that inhomogeneous liquid distribution may result in the formation of over wetted lumps. This was not observed with the 50 ll/min rate, which therefore was selected for all further experiments. The solid state of granulates prepared with 5% and 10% PVP in H2O binder solution is shown in Fig. 3. A PVP concentration of 20% in the granulate was prepared at room temperature by adding 50 ll/min of binding solution to 300 mg of ITZ loaded COK 12. In order to add the same amount of PVP to COK 12, 1500 ll and 750 ll of solvent need to be added for 5% and 10% w/v, respectively. Based on the enthalpy of melting, 1.52 0.5% of ITZ was released during the granulation step from the sample prepared with the 5% solution. Due to the lack of premature drug release observed with the 10% binder solution sample, this concentration was selected for all future developmental studies. Binder viscosity is recognized as an important parameter in controlling granulation behavior. Increasing the binder concentration would increase the viscosity, reduce the spreadi.