Blending homogeneity

Electron and optical microscopes are being used to see blend homogeneity. Elastomer-plastic blends are somewhat easier to identify than elastomer-elastomer blends because normal staining techniques, e.g., osmium tet-raoxide, can be used in the case of plastic-elastomer blends. Normally, there are two methods that are followed for examining the blend surface by electron microscopy. 

Processing Case Study Determining Blend Homogeneity Through Statistical Analysis... 

S.S. Sekulic, H.W. Ward, D.R. Brannegan, et al. On-line monitoring of powder blend homogeneity by near-infrared spectroscopy. Anal. Chem., 68, 509 - 513 (1996). 

R.C. Lyon, D.S. Lester, E.N. Lewis, E. Lee, L.X. Yu, E.H. Jefferson and A. S., Hussain, Near-infrared spectral imaging for quality assurance of pharmaceutical products analysis of tablets to assess powder blend homogeneity, AAPS Pharm. Sci. Tech., 3(3), 1-15 (2002). 

Given that NIRS is a rapid, nondestructive technique and that most pharmaceutical blend constituents absorb in the NIR, it has been applied off-line to assess blend homogeneity. In the mid-1990s scientists at Pfizer utilized on-line NIRS to successfully characterize powder blending. ... 

NIR methods are not the only on-line applications for blend monitoring FT-Raman " and laser induced fluorescence (LIF) have been utilized. Refer to Chapter 11 for a comprehensive review of LIF. As stated herein, NIRS is well established as an effective and advantageous means to deem blend homogeneity and blending end point, however there are circumstances in which NIR is insufficient. For example, LIF can be more suitable for blends with low drug load. Lai and Cooney illustrated in a lab-scale experiment that LIE yielded a limit of detection below 0.02% w/w for a given API. ... 

A.S. El-Hagrasy, F.D Amico and J.K. Drennen III, A process analytical technology approach to near-infrared process control of pharmaceutical powder blending. Part II Qualitiative near-infrared models for prediction of blend homogeneity, J. Pharm. ScL, 95(2), 407 21 (2006). 

Once the analytical method is validated for accuracy at the laboratory scale, it can be used to obtain extensive information on process performance (blend homogeneity, granulation particle size distribution, and moisture content) under various conditions (blender speed, mixing time, drying air temperature, humidity, volume, etc.). Statistical models can then be used to relate the observable variables to other performance attributes (e.g., tablet hardness, content uniformity, and dissolution) in order to determine ranges of measured values that are predictive of acceptable performance. 

In-process controls such as stratined sampling, process analytical technology (PAT) application, and blend homogeneity. Assess modincation of dissolution through optimization of API characteristics and then perform assessment of specialized technologies [hot-melt extrusion (HME), spray-dried dispersion, solid dispersion, etc.] for long-term resolution... 

Processing case study two Determining blend homogeneity through statistical analysis... 

Sekulic, S.S. Ward, H.W. Brannegan, D.R. Stanley, E.D. Evans, C.L. Sciavolino, S.T. Hailey, P.A. Aldridge, P.K., On-Line Monitoring of Powder Blend Homogeneity by Near-Infrared Spectroscopy Anal. Chem. 1996, 68, 509-513. 

Lyon, R.C. Lester, D.S. Lewis, E.N. Lee, E. Yu, L.X. Jefferson, E.H. 8t Hussain, A.S., Near-Infrared Spectral Imaging for Quality Assurance of Pharmaceutical Products Analysis of Tablets to Assess Powder Blend Homogeneity AAPS PharmSciTech. 2002, 3(3), article 17, 1-15. 

Lai, C.-K. Holt, D. Leung, J.C. etal., Real time and noninvasive monitoring of dry powder blend homogeneity AIChE J. 2001, 47, 2618-2622. 

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