Near-Infrared Spectroscopy for the In-Line Characterization of Powder Voiding Part II: Quantification of Enhanced Flow Properties of Surface Modified Active Pharmaceutical Ingredients

摘要

In this work, dry-particle coating was used to modify the surface properties of active pharmaceutical ingredients (APIs) having extremely poor flow properties. Near-infrared (NIR) spectroscopy was utilized as a novel approach to characterize the improved flow behavior of APIs and their blends. Acetaminophen and ibuprofen were coated with nano-sized silica at two different coating levels (0.5% and 1% w/w of the API) in dry-particle coating devices viz. magnetically assisted impaction coater (MAIC) and Hybridizer. Surface modified (dry coated) APIs were then blended with excipient (spray dried lactose monohydrate) in a V-blender. As a baseline comparison to dry coating, the silica addition was also accomplished by two commonly used industry methods, i.e., passing a portion of API with silica through a sieve (sieve blending method) or blending a portion of API powder with silica in a V-blender (preblending method). Flow results showed that dry particle coated acetaminophen as well as ibuprofen blends performed significantly better than uncoated API blends at higher API concentrations. In addition, examination of the flow intensity from NIR spectra (inverse signal to noise ratio of spectra) and its standard deviation revealed that dry particle coated blends showed better uniformity of flow as compared to the other methods. Angle of repose measurements corroborated these results, showing that the majority of the blends prepared from coated APIs stayed in either passable or fair category.