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

  • Lauren Beach
  • Jorge Ropero
  • Ajit Mujumdar
  • Manel Alcalà
  • Rodolfo J. Romañach
  • Rajesh N. DavéEmail author
Research Article

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.

Keywords

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

Notes

Acknowledgments

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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References

  1. 1.
    Thalberg K, Lindholm D, Axelsson A. Comparison of different flowability tests for powders for inhalation. Powder Technol. 2004;146:206–13.CrossRefGoogle Scholar
  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.CrossRefPubMedGoogle Scholar
  3. 3.
    Prescott JK, Barnum RA. On powder flowability. Pharm Technol. 2000;60–84.Google Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  6. 6.
    Lipinkski CA. Poor aqueous solubility—an industry wide problem in drug discovery. America Pharmaceutical Review. 2002;53:82.Google Scholar
  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.CrossRefGoogle Scholar
  8. 8.
    Molerus O. Effect of interparticle cohesive forces on the flow behavior of powders. Powder Technol. 1978;20:161–75.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.Google Scholar
  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.Google Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  16. 16.
    Mohan MR, Dave RN, Pfeffer R. The promotion of deactivated sintering by dry particle coating. AIChE J. 2003;49:604–18.CrossRefGoogle Scholar
  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.Google Scholar
  18. 18.
    Ridgway K, Scotton JB. Aspects of pharmaceutical engineering. Pharm J. 1972;208:574–6.Google Scholar
  19. 19.
    Duran J. The physics of fine powders: plugging and surface instabilities. Comptes Rendus Physique. 2002;3:217–27.CrossRefGoogle Scholar
  20. 20.
    Schwedes J. Review on testers for measuring flow properties of bulk solids. Granular Matter. 2003;5:1–43.CrossRefGoogle Scholar
  21. 21.
    Schulze D. Measuring powder flowability: a comparison of test methods—Part II. Powder Bulk Eng. 1996;10(6):17–28.Google Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefPubMedGoogle Scholar
  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.CrossRefPubMedGoogle Scholar
  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.CrossRefPubMedGoogle Scholar
  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.CrossRefPubMedGoogle Scholar
  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.CrossRefPubMedGoogle Scholar
  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.CrossRefPubMedGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefPubMedGoogle Scholar
  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.CrossRefPubMedGoogle Scholar
  33. 33.
    Food and Drug Administration. PAT—a framework for innovative pharmaceutical development, manufacturing, and quality assurance; 2004.Google Scholar
  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.Google Scholar
  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.CrossRefGoogle Scholar
  36. 36.
    Emery E, Oliver J, Pugsley T, Sharma J, Zhou J. Flowability of moist pharmaceutical powders. Powder Technol. 2009;189:409–15.CrossRefGoogle Scholar

Copyright information

© International Society for Pharmaceutical Engineering 2010

Authors and Affiliations

  • Lauren Beach
    • 1
  • Jorge Ropero
    • 2
  • Ajit Mujumdar
    • 1
  • Manel Alcalà
    • 3
  • Rodolfo J. Romañach
    • 2
  • Rajesh N. Davé
    • 1
    Email author
  1. 1.Department of Chemical, Biological and Pharmaceutical EngineeringNew Jersey Institute of TechnologyNewarkUSA
  2. 2.Department of ChemistryUniversity of Puerto RicoMayaguezUSA
  3. 3.Grup de Quimiometria Aplicada, Departament de Química (U. Analítica), Facultat de CiènciesUniversitat Autònoma de BarcelonaBellaterraSpain

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