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Lactose Composite Carriers for Respiratory Delivery

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Abstract

Purpose

Lactose dry powder inhaler (DPI) carriers, constructed of smaller sub units (composite carriers), were evaluated to assess their potential for minimising drug–carrier adhesion, variability in drug–carrier forces and influence on drug aerosol performance from carrier–drug blends.

Methods

Lactose carrier particles were prepared by fusing sub units of lactose (either 2, 6 or 10 μm) in saturated lactose slurry. The resultant composite particles, as well as supplied lactose, were sieve fractioned to obtain a 63–90 μm carriers. The carriers were evaluated in terms of size (laser diffraction) morphology (electron microscopy and atomic force microscopy), crystallinity and drug adhesion (colloid probe microscopy). In addition, blends containing drug and carrier were prepared and evaluated in terms of drug aerosol performance.

Results

The surface morphology and physico-chemical properties of the composite carriers were significantly different. Depending on the initial primary lactose size, the composite particles could be prepared with different surface roughness. Variation in composite roughness could be related to the change in drug adhesion (via modification in contact geometry) and thus drug aerosol performance from drug–lactose blends.

Conclusion

Composite based carriers are a potential route to control drug–carrier adhesion forces and variability thus allowing more precise control of formulation performance.

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References

  1. J. N. Pritchard. The influence of lung deposition on clinical response. J. Aerosol Med. 14:S19–S26 (2001). doi:10.1089/08942680150506303.

    Article  PubMed  CAS  Google Scholar 

  2. J. A. Hersey. Ordered mixing—new concept in powder mixing practice. Powder Technol. 11:41–44 (1975). doi:10.1016/0032-5910(75)80021-0.

    Article  Google Scholar 

  3. D. Cline, and R. Dalby. Predicting the quality of powders for inhalation from surface energy and area. Pharm. Res. 19:1274–1277 (2002). doi:10.1023/A:1020338405947.

    Article  PubMed  CAS  Google Scholar 

  4. R. Price, P. M. Young, S. Edge, and J. N. Staniforth. The influence of relative humidity on particulate interactions in carrier-based dry powder inhaler formulations. Int. J. Pharm. 246:47–59 (2002). doi:10.1016/S0378-5173(02)00359-9.

    Article  PubMed  CAS  Google Scholar 

  5. P. M. Young, A. Sung, D. Traini, P. Kwok, H. Chiou, and H. K. Chan. Influence of humidity on the electrostatic charge and aerosol performance of dry powder inhaler carrier based systems. Pharm. Res. 24:963–970 (2007). doi:10.1007/s11095-006-9218-8.

    Article  PubMed  CAS  Google Scholar 

  6. V. Berard, E. Lesniewska, C. Andres, D. Pertuy, C. Laroche, and Y. Pourcelot. Dry powder inhaler: influence of humidity on topology and adhesion studied by AFM. Int. J. Pharm. 232:213–224 (2002). doi:10.1016/S0378-5173(01)00913-9.

    Article  PubMed  CAS  Google Scholar 

  7. X. M. Zeng, H. B. MacRitchie, C. Marriott, and G. P. Martin. Humidity-induced changes of the aerodynamic properties of dry powder aerosol formulations containing different carriers. Int. J. Pharm. 333:45–55 (2007). doi:10.1016/j.ijpharm.2006.09.048.

    Article  PubMed  CAS  Google Scholar 

  8. N. Y. K. Chew, and H. K. Chan. Use of solid corrugated particles to enhance powder aerosol performance. Pharm. Res. 18:1570–1577 (2001). doi:10.1023/A:1013082531394.

    Article  PubMed  CAS  Google Scholar 

  9. N. Y. K. Chew, P. Tang, H. K. Chan, and J. A. Raper. How much particle surface corrugation is sufficient to improve aerosol performance of powders. Pharm. Res. 22:148–152 (2005). doi:10.1007/s11095-004-9020-4.

    Article  PubMed  CAS  Google Scholar 

  10. H. Adi, D. Traini, H. K. Chan, and P. M. Young. The influence of drug morphology on aerosolisation efficiency of dry powder inhaler formulations. J. Pharm. Sci. 97:2780–2788 (2008). doi:10.1002/jps.21195.

    Article  PubMed  CAS  Google Scholar 

  11. M. D. Louey, and P. J. Stewart. Particle interactions involved in aerosol dispersion of ternary interactive mixtures. Pharm. Res. 19:1524–1531 (2002). doi:10.1023/A:1020464801786.

    Article  PubMed  CAS  Google Scholar 

  12. N. Islam, P. Stewart, I. Larson, and P. Hartley. Lactose surface modification by decantation: are drug-fine lactose ratios the key to better dispersion of salmeterol xinafoate from lactose-interactive mixtures. Pharm. Res. 21:492–499 (2004). doi:10.1023/B:PHAM.0000019304.91412.18.

    Article  PubMed  CAS  Google Scholar 

  13. P. M. Young, D. Traini, H. K. Chan, H. Chiou, S. Edge, and T. Tee. The influence of mechanical processing dry powder inhaler carriers on drug aerosolisation performance. J. Pharm. Sci. 6:1331–1341 (2007). doi:10.1002/jps.20933.

    Article  Google Scholar 

  14. Y. Kawashima, T. Serigano, T. Hino, H. Yamamoto, and H. Takeuchi. Effect of surface morphology of carrier lactose on dry powder inhalation property of pranlukast hydrate. Int. J. Pharm. 172:179–188 (1998). doi:10.1016/S0378-5173(98)00202-6.

    Article  CAS  Google Scholar 

  15. F. Ferrari, D. Cocconi, R. Bettini, F. Giordano, P. Sant, M. J. Tobyn, R. Price, P. M. Young, C. Caramella, and P. Colombo. The surface roughness of lactose particles can be modulated by wet-smoothing using a high-shear mixer. AAPS PharmSciTech. 5:1–6 (2004). doi:10.1208/pt050460.

    Article  Google Scholar 

  16. D. El-Sabawi, S. Edge, R. Price, and P. Young. Continued investigation into the influence of loaded dose on the performance of dry powder inhalers: surface smoothing effects. Drug Dev. Ind. Pharm. 32:1135–1138 (2006). doi:10.1080/03639040600712920.

    Article  PubMed  CAS  Google Scholar 

  17. J. N. Staniforth. Pre-formulation aspects of dry powder aerosols. Proceedings of Respiratory Drug Delivery. 1:65–73 (1996).

    Google Scholar 

  18. P. M. Young, S. Edge, D. Traini, M. D. Jones, R. Price, D. El-Sabawi, C. Urry, and C. Smith. The influence of dose on the performance of dry powder inhalation systems. Int. J. Pharm. 296:26–33 (2005). doi:10.1016/j.ijpharm.2005.02.004.

    Article  PubMed  CAS  Google Scholar 

  19. K. Iida, Y. Hayakawa, H. Okamoto, K. Danjo, and H. Leuenberger. Preparation of dry powder inhalation by surface treatment of lactose carrier particles. Chem. Pharm. Bull. 51:1–5 (2003). doi:10.1248/cpb.51.1.

    Article  PubMed  CAS  Google Scholar 

  20. P. Begat, R. Price, H. Harris, D. A. V. Morton, and J. N. Staniforth. The influence of force control agents on the cohesive–adhesive balance in dry powder inhaler formulations. Kona. 23:109–121 (2005).

    CAS  Google Scholar 

  21. P. Lucas, K. Anderson, U. J. Potter, and J. N. Staniforth. Enhancement of small particle size dry powder aerosol formulations using an ultra low density additive. Pharm. Res. 16:1643–1647 (1999). doi:10.1023/A:1011981326827.

    Article  PubMed  CAS  Google Scholar 

  22. D. El-Sabawi, R. Price, S. Edge, and P. M. Young. Novel temperature controlled surface dissolution of excipient particles for carrier based dry powder inhaler formulations. Drug Dev. Ind. Pharm. 32:243–251 (2006). doi:10.1080/03639040500466395.

    Article  PubMed  CAS  Google Scholar 

  23. M. D. Louey, S. Razia, and P. J. Stewart. Influence of physico-chemical carrier properties on the in vitro aerosol deposition from interactive mixtures. Int. J. Pharm. 252:87–98 (2003). doi:10.1016/S0378-5173(02)00621-X.

    Article  PubMed  CAS  Google Scholar 

  24. P. M. Young, D. Roberts, H. Chiou, W. Rae, H. K. Chan, and D. Traini. Composite carriers improve the aerosolisation efficiency of drugs for respiratory delivery. J. Aerosol Sci. 39:82–93 (2007). doi:10.1016/j.jaerosci.2007.10.003.

    Article  Google Scholar 

  25. P. M. Young, D. Cocconi, P. Colombo, R. Bettini, R. Price, D. F. Steele, and M. J. Tobyn. Characterization of a surface modified dry powder inhalation carrier prepared by “particle smoothing”. J. Pharm. Pharmacol. 54:1339–1344 (2002). doi:10.1211/002235702760345400.

    Article  PubMed  CAS  Google Scholar 

  26. P. M. Young, R. Price, M. J. Tobyn, M. Buttrum, and F. Dey. Investigation into the effect of humidity on drug–drug interactions using the atomic force microscope. J. Pharm. Sci. 92:815–822 (2003). doi:10.1002/jps.10250.

    Article  PubMed  CAS  Google Scholar 

  27. P. M. Young, M. J. Tobyn, R. Price, M. Buttrum, and F. Dey. The use of colloid probe microscopy to predict aerosolization performance in dry powder inhalers: AFM and in vitro correlation. J. Pharm. Sci. 95:8100–1809 (2006).

    Google Scholar 

  28. J. H. Kirk, S. E. Dann, and C. G. Blatchford. Lactose: a definitive guide to polymorph determination. Int. J. Pharm. 334:103–114 (2007). doi:10.1016/j.ijpharm.2006.10.026.

    Article  PubMed  CAS  Google Scholar 

  29. J. H. Bushill, W. B. Wright, C. H. F. Fuller, and A. V. Bell. Crystallisation of lactose with particular reference to its occurrence in milk powder. J. Sci. Food Agric. 16:622–628 (1965). doi:10.1002/jsfa.2740161010.

    Article  PubMed  CAS  Google Scholar 

  30. R. Price, and P. M. Young. Visualization of the crystallization of lactose from the amorphous state. J. Pharm. Sci. 93:155–164 (2004). doi:10.1002/jps.10513.

    Article  PubMed  CAS  Google Scholar 

  31. O. C. Chidavaenzi, G. Buckton, F. Koosha, and R. Pathak. The use of thermal techniques to assess the impact of feed concentration on the amorphous content and polymorphic forms present in spray dried lactose. Int. J. Pharm. 159:67–74 (1997). doi:10.1016/S0378-5173(97)00272-X.

    Article  CAS  Google Scholar 

  32. W.C. Hinds. Aerosol Technology. Willey, New York, 1999.

    Google Scholar 

  33. D. Traini, F. Thielmann, M. Acharya, K. Jarring, and P. M. Young. The influence of lactose pseudopolymorphism on salbutamol sulphate–lactose interactions in DPI formulations. Drug Dev. Ind. Pharm. 34:992–1001.

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Authors and Affiliations

  1. Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia

    Paul M. Young, Philip Kwok, Handoko Adi, Hak-Kim Chan & Daniela Traini

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  1. Paul M. Young
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  2. Philip Kwok
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  3. Handoko Adi
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  4. Hak-Kim Chan
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  5. Daniela Traini
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Correspondence to Paul M. Young.

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Young, P.M., Kwok, P., Adi, H. et al. Lactose Composite Carriers for Respiratory Delivery. Pharm Res 26, 802–810 (2009). https://doi.org/10.1007/s11095-008-9779-9

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  • DOI: https://doi.org/10.1007/s11095-008-9779-9

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