It had previously been determined that overhead stirring was not suitable for preparation of the HEC-based semi-solids due to the high rate of shear required U0126 manufacturer to achieve uniform mixing, excessive aeration and the potential for high shearing stresses to trigger mechanical breakdown of the polymeric components. To overcome this, mixing was carried out under vacuum with the use of the HiVac® mixing bowl. Following dispensing trials a number of semi-solid formulations
were selected for rheological flow analysis. The influence of shear rate on the shear viscosity of the selected HEC- and NaCMC-based semi-solids is shown in Fig. 1a and b, respectively. Flow analysis showed that all the semi-solid formulations were pseudoplastic in nature in that they displayed decreasing shear viscosity with increasing shear rate. The power law function was used to determine flow consistency (κ) of the materials understudy (at 1 s−1) ( Table 2). On the basis of rheological analysis and dispensing trials, determined by viscosity and ability to settle into blister pack wells, formulations containing Blanose 7LF were chosen for lyophilization. Obeticholic Acid For all semi-solid formulations in the absence and presence of CN54gp140, the glass transition
temperature was identified between −21 and −22 °C. Three solid dosage forms with different dimensions were prepared (Fig. 2a–c). LSDFs containing 10% Blanose 7LF were inconsistent in structure whereas those containing lower levels of Blanose 7LF provided uniform units suitable for further investigation.
Following friability testing no lyophilized solid dosage formulation tested (both those shown in Fig. 2a and b) was subject to fracture or exterior damage. No loss of weight occurred whereas slight increases in weight were detected (<8%). Following reconstitution of the LSDFs designed for i.vag administration (Fig. 2a) in SVF (1 tablet per 1 ml) oscillatory (dynamic) analysis (a measure ADAMTS5 of consistency) was performed on the resulting semi-solid structure at 37 °C and compared to the original equivalent semi-solid formulations pre-lyophilization (Table 2). The percentage cumulative release of CN54gp140 from solid dosage formulations (formulation type – Fig. 2b) containing Blanose 7LF at 3, 5 and 10% is shown in Fig. 3. Release profiles of CN54gp140 were similar, displaying a continuous release of antigen with maximum CN54gp140 detectable (Tmax) in the dissolution media after a 7–8 h period (Table 3). The percentage cumulative release of CN54gp140 from solid dosage formulations (formulation type – Fig. 2c) lyo-PC3HEC250HHX5PVP4, lyo-PC3Blanose7LF3PVP4 and lyo-Carbopol® going forward to the mouse immunogenicity study are shown in Fig. 4. Stability of CN54gp140 within the lyophilized solid dosage tablet formulation (Formulation type – Fig.