Erythromycin Stearate

A commonly used strategy to improve aerosolization behavior of carrier-based dry powder inhalers (DPIs) is the addition of magnesium stearate as a lubricant, yet it may also negatively affect properties of DPIs. Thus, the aim of this study was to find lubricants that could be used as alternatives of magnesium stearate and meanwhile verify the applicability of using powder rheological properties to predict the performance of different lubricants in DPIs. Here, using fluticasone propionate as a model drug, LH200 as the carrier, influence of lubricants type and particle size, including magnesium stearate, sodium stearate, Leucine, sodium stearate fumarate, Compritol® 888 ATO, and Compritol® HD5 ATO, on the physicochemical properties, powder rheology and aerosolization behavior of the DPI formulations was characterized. Further, the relationship between powder rheological parameters and in-vitro drug deposition parameter, fine particle fraction (FPF), were explored, and the contribution of powder flowability and adhesion was evaluated using principal component analysis (PCA). The results showed that magnesium stearate, sodium stearate and smaller sized leucine significantly reduced the basic flowability energy, aeration energy and Permeability of the DPI formulations, leading to improved aerosolization behavior. A robust linear correlation was established between rheological parameters and FPF. PCA showed that in lubricants containing formulations, the contribution of flowability (74.69%) was greater than that of adhesion (25.31%). In conclusion, sodium stearate and smaller particle size Leucine can be considered as substitutes of magnesium stearate in DPI formulations.

The continuous feeding-mixing system ensures the composition uniformity down to the tableting continuous manufacturing line so that a quality end-product is consistently delivered. Near-infrared spectroscopy (NIRS) enables in-line assessment of the blend's critical quality attributes in real-time. In this study, the effect of total feed rate and impeller speed on the continuous blending process monitored in-line by NIRS was examined by principal component analysis (PCA), ANOVA simultaneous component analysis (ASCA) and partial least squares (PLS) regression. Process data were generated by a factorial experimental design with process parameters and a constant formulation comprised of: 30 % (wt/wt) ibuprofen, 67.5 % (wt/wt) microcrystalline cellulose, 2 % (wt/wt) of sodium starch glycolate and 0.5 % (wt/wt) of magnesium stearate. The PCA hinted at the prevalence of impeller speed effect on ibuprofen concentration due to path length variation of the NIR light caused by the fluidized behaviour in the powder blend as a result of high speed ranges (>300 rpm). The ASCA model indicated that while both impeller speed and total feed rate effects were statistically significant (p-value=0.004), the impeller speed was the factor that contributed the most to the spectral variance (55.5 %). The PLS regression model for the ibuprofen content resulted in a RMSECV of 1.3 % (wt/wt) and showed that impeller speed was yet again the factor that exerted the major influence on spectral variance, owing to its wavelength-dependent effect that prevents common pre-processing techniques from eliminating it across the entire NIR range. The best sample presentation to the NIR probe was achieved at low impeller speed ranges (<600 rpm) and low total feed rates (<15 kg/h), such that it enhanced the PLS model ability to predict the ibuprofen concentration in the blend.