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

Abstract

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.

Fluid bed film coating of fine ibuprofen particles

“…Similar to the current results, previous studies have demonstrated that in some cases, the addition of nano-silica particles through low intensity methods (i.e. hand mixing or v-blending) can offer substantial flow improvements, although high intensity dry 13 coating performed by MAIC [24,[30][31][32][33][34], LabRAM [26], or Fluid Energy Milling [6,27] leads to better improvements. As mentioned before, Yang et al proposed that the flow improvements were due to the introduction of nano-sized surface asperities in the form of the guest particle [24].…”

“…Several methods have been developed to achieve high quality surface coatings in a dry process [6,[23][24][25][26][27][28][29]. These methods have been shown to offer substantial flow improvements by simultaneously deagglomerating the cohesive nano-silica, i.e., glidant powders, and dispersing the nano-silica particles across the host or carrier particle surface, which include Magnetically Assisted Impaction Coating [24,[30][31][32][33][34], Acoustic Mixing [26], and Fluid Energy Milling [6,27]. Yang et al derived a simple equation that showed that the reduction in cohesion due to the introduction of the nano-sized surface asperity in the form of the nanosilica coating is inversely proportional to particle size [24], hence coating of nano-silica would lead to improvements in the flow properties.…”

Near Infrared Method Development for a Continuous Manufacturing Blending Process

“…Colloidal silicon dioxide (SiO 2 ) was placed over the ibuprofen along with a portion of preweighed lactose in order to prevent the cohesive mixture from sticking to the sieve. Components were rubbed together through the sieve [13]. This preliminary mixture was used as the API preblend.…”

High energy dry coating mixing: Elements on velocities, temperatures and melting

“…The Hybridizer from Nara Machinery is a high energy mixer that has been often used in the literature to carry out dry coating [2][3][4].…”