Advertisement

Pharmaceutical Research

, 36:43 | Cite as

Particle Surface Roughness Improves Colloidal Stability of Pressurized Pharmaceutical Suspensions

  • Hui Wang
  • David S. Nobes
  • Reinhard VehringEmail author
Research Paper

Abstract

Purpose

The effects of particle size and particle surface roughness on the colloidal stability of pressurized pharmaceutical suspensions were investigated using monodisperse spray-dried particles.

Methods

The colloidal stability of multiple suspensions in the propellant HFA227ea was characterized using a shadowgraphic imaging technique and quantitatively compared using an instability index. Model suspensions of monodisperse spray-dried trehalose particles of narrow distributions (GSD < 1.2) and different sizes (MMAD = 5.98 μm, 10.1 μm, 15.5 μm) were measured first to study the dependence of colloidal stability on particle size. Particles with different surface rugosity were then designed by adding different fractions of trileucine, a shell former, and their suspension stability measured to further study the effects of surface roughness on the colloidal stability of pressurized suspensions.

Results

The colloidal stability significantly improved (p < 0.001) from the suspension with 15.5 μm-particles to the suspension with 5.98 μm-particles as quantified by the decreased instability index from 0.63 ± 0.04 to 0.07 ± 0.01, demonstrating a strongly size-dependent colloidal stability. No significant improvement of suspension stability (p > 0.1) was observed at low trileucine fraction at 0.4 % where particles remained relatively smooth until the surface rugosity of the particles was improved by the higher trileucine fractions at 1.0 % and 5.0 %, which was indicated by the substantially decreased instability index from 0.27 ± 0.02 for the suspensions with trehalose model particles to 0.18 ± 0.01 (p < 0.01) and 0.03 ± 0.01 (p < 0.002) respectively.

Conclusions

Surface modification of particles by adding shell formers like trileucine to the feed solutions of spray drying was demonstrated to be a promising method of improving the colloidal stability of pharmaceutical suspensions in pressurized metered dose inhalers.

Key words

monodisperse spray drying particle formation shadowgraphic imaging surface roughness suspension stability 

Notes

Acknowledgments and Disclosures

The authors acknowledge financial support from the Natural Sciences and Engineering Research Council (NSERC) of Canada, the Alberta Ingenuity Fund and the Canadian Foundation for Innovation (CFI). Hui Wang gratefully acknowledges the scholarship support of Alberta Innovates and Alberta Advanced Education.

References

  1. 1.
    Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today. 2007;12(23):1068–75.PubMedGoogle Scholar
  2. 2.
    Kipp J. The role of solid nanoparticle technology in the parenteral delivery of poorly water-soluble drugs. Int J Pharm. 2004;284(1–2):109–22.PubMedGoogle Scholar
  3. 3.
    Huang J, Wigent RJ, Bentzley CM, Schwartz JB. Nifedipine solid dispersion in microparticles of ammonio methacrylate copolymer and ethylcellulose binary blend for controlled drug delivery: effect of drug loading on release kinetics. Int J Pharm. 2006;319(1–2):44–54.PubMedGoogle Scholar
  4. 4.
    Müller RH, MaÈder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery–a review of the state of the art. Eur J Pharm Biopharm. 2000;50(1):161–77.PubMedGoogle Scholar
  5. 5.
    Kleinstreuer C, Zhang Z, Donohue J. Targeted drug-aerosol delivery in the human respiratory system. Annu Rev Biomed Eng. 2008;10:195–220.PubMedGoogle Scholar
  6. 6.
    Heyder J. Deposition of inhaled particles in the human respiratory tract and consequences for regional targeting in respiratory drug delivery. Proc Am Thorac Soc. 2004;1(4):315–20.PubMedGoogle Scholar
  7. 7.
    Ooi J, Traini D, Boyd BJ, Gaisford S, Young PM. Determination of physical and chemical stability in pressurised metered dose inhalers: potential new techniques. Expert Opin Drug Deliv. 2015;12(10):1661–75.PubMedGoogle Scholar
  8. 8.
    Stein SW, Sheth P, Hodson PD, Myrdal PB. Advances in metered dose inhaler technology: hardware development. AAPS PharmSciTech. 2014;15(2):326–38.PubMedGoogle Scholar
  9. 9.
    Ivey JW, Vehring R, Finlay WH. Understanding pressurized metered dose inhaler performance. Expert Opin Drug Deliv. 2015;12(6):901–16.PubMedGoogle Scholar
  10. 10.
    DeCarlo PF, Slowik JG, Worsnop DR, Davidovits P, Jimenez JL. Particle morphology and density characterization by combined mobility and aerodynamic diameter measurements. Part 1: theory. Aerosol Sci Technol. 2004;38(12):1185–205.Google Scholar
  11. 11.
    Israelachvili JN. Intermolecular and surface forces: revised third edition: Academic Press; 2011.Google Scholar
  12. 12.
    Johnson KA. Interfacial phenomena and phase behavior in metered dose inhaler formulations. In: Lung biology in health and disease; 1996. p. 385–415.Google Scholar
  13. 13.
    Rogueda P. Novel hydrofluoroalkane suspension formulations for respiratory drug delivery. Expert Opin Drug Deliv. 2005;2(4):625–38.PubMedGoogle Scholar
  14. 14.
    Finlay WH. The mechanics of inhaled pharmaceutical aerosols: an introduction: Academic Press; 2001.Google Scholar
  15. 15.
    Myrdal PB, Sheth P, Stein SW. Advances in metered dose inhaler technology: formulation development. AAPS PharmSciTech. 2014;15(2):434–55.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Arora P, Kumar L, Vohra V, Sarin R, Jaiswal A, Puri M, et al. Evaluating the technique of using inhalation device in COPD and bronchial asthma patients. Respir Med. 2014;108(7):992–8.PubMedGoogle Scholar
  17. 17.
    Dellamary LA, Tarara TE, Smith DJ, Woelk CH, Adractas A, Costello ML, et al. Hollow porous particles in metered dose inhalers. Pharm Res. 2000;17(2):168–74.PubMedGoogle Scholar
  18. 18.
    Hirst PH, Pitcairn GR, Weers JG, Tarara TE, Clark AR, Dellamary LA, et al. In vivo lung deposition of hollow porous particles from a pressurized metered dose inhaler. Pharm Res. 2002;19(3):258–64.PubMedGoogle Scholar
  19. 19.
    Rabinow BE. Nanosuspensions in drug delivery. Nat Rev Drug Discov. 2004;3(9):785–96.PubMedGoogle Scholar
  20. 20.
    Patravale V, Kulkarni R. Nanosuspensions: a promising drug delivery strategy. J Pharm Pharmacol. 2004;56(7):827–40.PubMedGoogle Scholar
  21. 21.
    Lieberman HA, Rieger MM, Banker GS. Pharmaceutical dosage forms: disperse systems. New York: Marcel Dekker; 1996.Google Scholar
  22. 22.
    Smyth HD. The influence of formulation variables on the performance of alternative propellant-driven metered dose inhalers. Adv Drug Del Rev. 2003;55(7):807–28.Google Scholar
  23. 23.
    Williams RO, Repka M, Liu J. Influence of propellant composition on drug delivery from a pressurized metered-dose inhaler. Drug Dev Ind Pharm. 1998;24(8):763–70.PubMedGoogle Scholar
  24. 24.
    Wu L, Zhang J, Watanabe W. Physical and chemical stability of drug nanoparticles. Adv Drug Del Rev. 2011;63(6):456–69.Google Scholar
  25. 25.
    Selvam P, Peguin RP, Chokshi U, da Rocha SR. Surfactant design for the 1, 1, 1, 2-tetrafluoroethane− water interface: ab initio calculations and in situ high-pressure tensiometry. Langmuir. 2006;22(21):8675–83.PubMedGoogle Scholar
  26. 26.
    Adi S, Adi H, Tang P, Traini D, H-k C, Young PM. Micro-particle corrugation, adhesion and inhalation aerosol efficiency. Eur J Pharm Sci. 2008;35(1–2):12–8.PubMedGoogle Scholar
  27. 27.
    Young PM, Price R, Lewis D, Edge S, Traini D. Under pressure: predicting pressurized metered dose inhaler interactions using the atomic force microscope. J Colloid Interface Sci. 2003;262(1):298–302.PubMedGoogle Scholar
  28. 28.
    Traini D, Rogueda P, Young P, Price R. Surface energy and interparticle force correlation in model pMDI formulations. Pharm Res. 2005;22(5):816–25.PubMedGoogle Scholar
  29. 29.
    Traini D, Young PM, Rogueda P, Price R. In vitro investigation of drug particulates interactions and aerosol performance of pressurised metered dose inhalers. Pharm Res. 2007;24(1):125–35.PubMedGoogle Scholar
  30. 30.
    D’Sa D, Chan H-K, Chrzanowski W. Predicting physical stability in pressurized metered dose inhalers via dwell and instantaneous force colloidal probe microscopy. Eur J Pharm Biopharm. 2014;88(1):129–35.PubMedGoogle Scholar
  31. 31.
    Baldelli A, Vehring R. Analysis of cohesion forces between monodisperse microparticles with rough surfaces. Colloid Surface A. 2016;506:179–89.Google Scholar
  32. 32.
    Mengual O, Meunier G, Cayré I, Puech K, Snabre P. TURBISCAN MA 2000: multiple light scattering measurement for concentrated emulsion and suspension instability analysis. Talanta. 1999;50(2):445–56.PubMedGoogle Scholar
  33. 33.
    Voss A, Finlay WH. Deagglomeration of dry powder pharmaceutical aerosols. Int J Pharm. 2002;248(1–2):39–50.PubMedGoogle Scholar
  34. 34.
    Vehring R, Foss WR, Lechuga-Ballesteros D. Particle formation in spray drying. J Aerosol Sci. 2007;38(7):728–46.Google Scholar
  35. 35.
    Lechuga-Ballesteros D, Charan C, Stults CLM, Stevenson CL, Miller DP, Vehring R, et al. Trileucine improves aerosol performance and stability of spray-dried powders for inhalation. J Pharm Sci. 2008;97(1):287–302.PubMedGoogle Scholar
  36. 36.
    Azhdarzadeh M, Shemirani FM, Ruzycki CA, Baldelli A, Ivey J, Barona D, et al. An atomizer to generate monodisperse droplets from high vapor pressure liquids. Atomization Sprays. 2016;26(2):121–34.Google Scholar
  37. 37.
    Ivey JW, Bhambri P, Church TK, Lewis DA, Vehring R. Experimental investigations of particle formation from propellant and solvent droplets using a monodisperse spray dryer. Aerosol Sci Technol. 2018:1–15.Google Scholar
  38. 38.
    Sirignano W, Mehring C. Review of theory of distortion and disintegration of liquid streams. Prog Energy Combust Sci. 2000;26(4–6):609–55.Google Scholar
  39. 39.
    Vehring R. Pharmaceutical particle engineering via spray drying. Pharm Res. 2008;25(5):999–1022.PubMedGoogle Scholar
  40. 40.
    Boraey MA, Vehring R. Diffusion controlled formation of microparticles. J Aerosol Sci. 2014;67:131–43.Google Scholar
  41. 41.
    Wang H, Barona D, Oladepo S, Williams L, Hoe S, Lechuga-Ballesteros D, et al. Macro-Raman spectroscopy for bulk composition and homogeneity analysis of multi-component pharmaceutical powders. J Pharm Biomed Anal. 2017;141:180–91.PubMedGoogle Scholar
  42. 42.
    Rouquerol F, Rouquerol J, Sing KS, Llewellyn P, Maurin G. Adsorption by powders and porous solids: principles, methodology and applications: Academic press; 2014.Google Scholar
  43. 43.
    Wang H, Tan P, Barona D, Li G, Hoe S, Lechuga-Ballesteros D, et al. Characterization of the suspension stability of pharmaceuticals using a Shadowgraphic imaging method. Int J Pharm. 2018;548(1):128–38.PubMedGoogle Scholar
  44. 44.
    Zhang J, Zografi G. Water vapor absorption into amorphous sucrose-poly (vinyl pyrrolidone) and trehalose–poly (vinyl pyrrolidone) mixtures. J Pharm Sci. 2001;90(9):1375–85.PubMedGoogle Scholar
  45. 45.
    Wang H, Boraey MA, Williams L, Lechuga-Ballesteros D, Vehring R. Low-frequency shift dispersive Raman spectroscopy for the analysis of respirable dosage forms. Int J Pharm. 2014;469(1):197–205.PubMedGoogle Scholar
  46. 46.
    Hédoux A. Recent developments in the Raman and infrared investigations of amorphous pharmaceuticals and protein formulations: a review. Adv Drug Del Rev. 2016;100:133–46.Google Scholar
  47. 47.
    Hinds WC. Aerosol technology: properties, behavior, and measurement of airborne particles. New York: John Wiley & Sons; 2012.Google Scholar
  48. 48.
    Cheng W, Dunn P, Brach R. Surface roughness effects on microparticle adhesion. J Adhes. 2002;78(11):929–65.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Mechanical Engineering, 10-269 Donadeo Innovation Centre for EngineeringUniversity of AlbertaEdmontonCanada

Personalised recommendations