In-process rheometry as a PAT tool for hot melt extrusion.

Real time measurement of melt rheology has been investigated as a Process Analytical Technology (PAT) to monitor hot melt extrusion of an Active Pharmaceutical Ingredient (API) in a polymer matrix. A developmental API was melt mixed with a commercial copolymer using a heated twin screw extruder at different API loadings and set temperatures. The extruder was equipped with an instrumented rheological slit die which incorporated three pressure transducers flush mounted to the die surface. Pressure drop measurements within the die at a range of extrusion throughputs were used to calculate rheological parameters, such as shear viscosity and exit pressure, related to shear and elastic melt flow properties, respectively. Results showed that the melt exhibited shear thinning behavior whereby viscosity decreased with increasing flow rate. Increase in drug loading and set extrusion temperature resulted in a reduction in melt viscosity. Shear viscosity and exit pressure measurements were found to be sensitive to API loading. These findings suggest that this technique could be used as a simple tool to measure material attributes in-line, to build better overall process understanding for hot melt extrusion.

Correlation of lipid layer thickness measurements with fluorescein tear film break-up time and Schirmer's test.

PURPOSE: This study correlates measurement of lipid layer thickness (LLT) with two frequently used dry eye tests, fluorescein break-up time (FBUT) and Schirmer's test with anaesthesia (STA). METHODS: Subjects (n = 44 eyes) with symptoms of dry eye and positive results for dry eye with either FBUT or STA or both were selected. Quantification of LLT was performed by the observation of colour interference patterns in zones of specular reflection using a custom-designed instrument. RESULTS: All correlations among pairs of tests were strong and exhibited a significance of P < 0.000: STA with FBUT, Pearson's correlation 0.653; STA with LLT, 0.764; FBUT with LLT, 0.751. When LLT was high, ie > or = 120 nm, which occurred in 14 eyes, STA was also elevated in those eyes and FBUT was high in 13 of the 14 eyes. When LLT was low, ie < or = 60, which occurred in 22 eyes, STA was below normal in 14 of the 22 eyes, and FBUT was below normal in 15 of the 22 eyes. These clinical observations paralleled the statistical findings computed from the entire data set. CONCLUSIONS: The correlations demonstrated in this study support the premise (1) that measurement of LLT is a reliable test for the diagnosis of dry eye, and (2) that aqueous deficiency and lipid deficiency, as they apply to dry eye disorders, are not mutually exclusive.