No abstract

Continuous manufacturing, a gaining interest paradigm in the pharmaceutical industry, requires in-process monitoring of critical process parameters to ensure product consistency. This study demonstrated the application of Fourier transform near-infrared (FT-NIR) spectroscopy in conjunction with chemometrics modeling for in-line hot melt extrusion process monitoring. The obtained results suggested that inline FT-NIR analysis, along with a tailored NIR reflector, is a viable process analytical tool to monitor active pharmaceutical ingredient concentration as well as processing parameters.

Paper sheet material has a high toughness and a low yield stress so that linear elastic fracture mechanics is inappropriate to measure its fracture resistance. Experiments have been conducted on single edge-notched tension SE(T) specimens using the J-integral analysis but there are difficulties in identifying the crack initiation, and the Jc value at 0.2 mm crack growth as required by ASTM E813-89 depends on the slope of the JR-curve which may be affected by specimen size and geometry effects. To overcome these problems the essential fracture work concept is applied to paper and an experimental technique developed to evaluate the specific fracture energy using deeply double-edge notched tension DE(T) specimens containing different ligament lengths. With this technique the fracture resistance of papers from hardwood and softwood pulps, the effects of level of bonding and recycling can be compared. It is recommended that the essential fracture work method be used for quality control of paper by the pulp and paper industry.

Delayed-release dosage forms are mainly manufactured as batch processes and include coated tablets, pellets, or particles with gastric resistant polymers. Authors propose a novel approach using the hot-melt extrusion technique to prepare delayed release dosage forms via a continuous manufacturing process, a new trend in the pharmaceutical industry. A full factorial design was employed to correlate input variables, including stearic acid (SA) content, drug content, and pellet size with drug release properties of the pellets. PLS fit method suitably elaborated the relationship between input and output variables with reasonably good fit and goodness of prediction. All three input factors influenced drug release in enzyme-free simulated gastric fluid (SGF) after 120 min; however, SA content did not significantly affect drug dissolution in the enzyme-free simulated intestinal fluid (SIF). An optimized formulation and design space were determined by overlaying multiple contours established from regression equations. The continuous manufacturing process was successfully monitored using inline near-infrared (NIR) and inline particle size analysis, with drug load and pellet size being well-controlled within the design space. The obtained pellets released less than 5% after 120 min in SGF and more than 85% and 95% after 30 min and 45 min, respectively, after switching to SIF.