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


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.

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  1. 1.

    Thalberg K, Lindholm D, Axelsson A. Comparison of different flowability tests for powders for inhalation. Powder Technol. 2004;146:206–13.

  2. 2.

    Lindberg N et al. Flowability measurements of pharmaceutical powder mixtures with poor flow using five different techniques. Drug Dev Ind Pharm. 2004;30:785–91.

  3. 3.

    Prescott JK, Barnum RA. On powder flowability. Pharm Technol. 2000;60–84.

  4. 4.

    Mosharraf M, Nyström C. The effect of particle size and shape on the surface specific dissolution rate of micronized practically insoluble drugs. Int J Pharm. 1995;122:35–47.

  5. 5.

    Noyes AA, Whitney WR. The rate of solution of solid substances in their own solutions. J Am Chem Soc. 1897;19(12):930.

  6. 6.

    Lipinkski CA. Poor aqueous solubility—an industry wide problem in drug discovery. America Pharmaceutical Review. 2002;53:82.

  7. 7.

    Liversidge GG, Cundy KC. Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: absolute oral bioavailability of nanocrystalline Danzol in beagle dogs. Int J Pharm. 1995;125:91.

  8. 8.

    Molerus O. Effect of interparticle cohesive forces on the flow behavior of powders. Powder Technol. 1978;20:161–75.

  9. 9.

    Kono HO, Huang CC, Xi M. Function and mechanism of flow conditioners under various loading pressure conditions in bulk powders. Powder Technol. 1990;63:81–6.

  10. 10.

    Kaya BH, Leblanc JE, Moxam D, Zubac D. The effect of vibration on the rheology of powders. International Powder and Bulk Solids Handling and Processing. 1983;324–37.

  11. 11.

    Elbicki JM, Tardos GI. The influence of fines on the flowability of alumina powders in test hoppers. Powder Handl Proc. 1998;10(2):147–49.

  12. 12.

    Pfeffer R, Wei D, Dave R, Ramlakhan M. Synthesis of engineered particulates with tailored properties using dry particle coating. Powder Technol. 2001;117:40–67.

  13. 13.

    Ramlakhan M, Wu CY, Watano S, Dave R, Pfeffer R. Dry particle coating using magnetically assisted impaction coating. Powder Technol. 2000;112:137–48.

  14. 14.

    Mujumdar A, Wei D, Dave R, Pfeffer R, Wu CY. Improvement of humidity resistance of magnesium powder using dry particle coating. Powder Technol. 2004;140:86–97.

  15. 15.

    Yang J, Silva A, Banerjee A, Dave R, Pfeffer R. Dry particle coating for improving the flowability of cohesive powders. Powder Technol. 2005;158:21–33.

  16. 16.

    Mohan MR, Dave RN, Pfeffer R. The promotion of deactivated sintering by dry particle coating. AIChE J. 2003;49:604–18.

  17. 17.

    Castellanos A. The Sevilla powder tester: a tool for characterizing the physical properties of fine cohesive powders at very small consolidations. KONA. 2004;22:66–81.

  18. 18.

    Ridgway K, Scotton JB. Aspects of pharmaceutical engineering. Pharm J. 1972;208:574–6.

  19. 19.

    Duran J. The physics of fine powders: plugging and surface instabilities. Comptes Rendus Physique. 2002;3:217–27.

  20. 20.

    Schwedes J. Review on testers for measuring flow properties of bulk solids. Granular Matter. 2003;5:1–43.

  21. 21.

    Schulze D. Measuring powder flowability: a comparison of test methods—Part II. Powder Bulk Eng. 1996;10(6):17–28.

  22. 22.

    Ropero J, Beach L, Alcalà M, Rentas R, Dave R, Romanach R. Near-infrared spectroscopy for the in-line characterization of powder voiding part I: development of the methodology. Submitted for the publication concurrently with the present manuscript in Journal of Pharmaceutical Innovation, 2009. doi:10.1007/s12247-009-9069-z.

  23. 23.

    Berntsson O, Danielsson LG, Lagerholm B, Folestad S. Quantitative in-line monitoring of powder blending by near infrared reflection spectroscopy. Powder Technol. 2002;123:185–93.

  24. 24.

    Bellamy LJ, Nordon A, Littlejohn D. Real-time monitoring of powder mixing in a convective blender using non-invasive reflectance NIR spectrometry. Analyst. 2008;133:58–64.

  25. 25.

    Alcalà M, León J, Ropero J, Blanco M, Romañach R. Analysis of low content drug tablets by transmission near infrared spectroscopy: selection of calibration ranges according to multivariate detection and quantitation limits of PLS models. J Pharm Sci. 2008;97(12):5318–27.

  26. 26.

    El-Hagrasy AS, D’Amico F, Drennen JK. A process analytical technology approach to near-infrared process control of pharmaceutical powder blending. Part I: D-optimal design for characterization of powder mixing and preliminary spectral data evaluation. J Pharm Sci. 2006;95(2):392–406.

  27. 27.

    El-Hagrasy AS, Delgado López M, Drennen JK. A process analytical technology approach to near-infrared process control of pharmaceutical powder blending: Part II: qualitative near-infrared models for prediction of blend homogeneity. J Pharm Sci. 2006;95(2):407–21.

  28. 28.

    Shi Z, Cogdill RP, Short SM, Anderson CA. Process characterization of powder blending by near-infrared spectroscopy: blend end-points and beyond. J Pharm Biomed Anal. 2008;47:738–45.

  29. 29.

    Green RL, Thurau G, Pixley NC, Mateos A, Reed RA, Higgins JP. In-line monitoring of moisture content in fluid bed dryers using Near-IR spectroscopy with consideration of sampling effects on method accuracy. Anal Chem. 2005;77:4515–22.

  30. 30.

    Faqih AM, Alexander AW, Muzzio FJ, Tomassone MS. A method for predicting hopper flow characteristics of pharmaceutical powders. Chem Eng Sci. 2007;62:1536–42.

  31. 31.

    Faqih AM, Chaudhuri B, Alexander AW, Davies C, Muzzio FJ, Tomassone MS. An experimental/computational approach for examining unconfined cohesive powder flow. Int J Pharm. 2006;324:116–27.

  32. 32.

    Hailey PA, Doherty P, Tapsell P, Oliver T, Aldridge PK. Automated system for the on-line monitoring of powder blending processes using near-infrared spectroscopy part I. System development and control. J Pharm Biomed Anal. 1996;14:551–9.

  33. 33.

    Food and Drug Administration. PAT—a framework for innovative pharmaceutical development, manufacturing, and quality assurance; 2004.

  34. 34.

    International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline, Pharmaceutical Development Q8, Step 5, 10-November-2005.

  35. 35.

    Zhou YC, Xu BH, Yu AB, Zulli P. An experimental and numerical study of the angle of repose of coarse spheres. Powder Technol. 2002;125:45–54.

  36. 36.

    Emery E, Oliver J, Pugsley T, Sharma J, Zhou J. Flowability of moist pharmaceutical powders. Powder Technol. 2009;189:409–15.

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Authors acknowledge the National Science Foundation (ERC research grant: EEC-0540855) for providing support for this collaborative research. Thanks are also due to Raizza Rentas and Hendri Chauca for their contributions to the experimental work which they did during their summer REU (Research Experience for Undergraduates) program at NJIT.

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Correspondence to Rajesh N. Davé.

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Beach, L., Ropero, J., Mujumdar, A. et al. Near-Infrared Spectroscopy for the In-Line Characterization of Powder Voiding Part II: Quantification of Enhanced Flow Properties of Surface Modified Active Pharmaceutical Ingredients. J Pharm Innov 5, 1–13 (2010).

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  • Dry-particle coating
  • Flow improvement of APIs
  • Flow uniformity
  • Near-infrared spectroscopy
  • Angle of repose
  • Flow additives
  • Surface modification
  • Nano silica