Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2004 December; 5(4): 69–74.
Published online 2004 September 8. doi:  10.1208/pt050460
PMCID: PMC2750485

The surface roughness of lactose particles can be modulated by wet-smoothing using a high-shear mixer


The surface morphology of α-lactose monohydrate particles was modified by a new wet-smoothing process performed in a high-shear mixer using solvents. Successive steps of wetting and drying of lactose powders during rolling in the mixer's cylindrical bowl were performed. Smoothed particles were tested for size distribution, flow, and packing. The wet-smoothing process flattened the surface and rounded the edges of lactose particles. In comparison with original lactose, an improvement of powder packing and flow properties was evidenced. When the process was performed in the presence of a ternary agent such as magnesium stearate, the smoothing was improved. The evolution of rugosity during the smoothing process was assessed through a fractal descriptor of SEM picture. Atomic force microscopy and surface area measurements quantified the surface rugosity. A very significant reduction of the rugosity, more remarkable in the presence of magnesium stearate, was measured. This new process of powder wet-smoothing allows the preparation of lactose particles with different degrees of smoothed surface for the control of flow and packing properties and particle-particle interactions.

Keywords: lactose, smoothing, roughness, high-shear mixer

Full Text

The Full Text of this article is available as a PDF (752K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Bell JH, Hartley PS, Cox JSG. Dry powder aerosol I: a new powder inhalation device. J Pharm Sci. 1971;60:1559–1564. doi: 10.1002/jps.2600601028. [PubMed] [Cross Ref]
2. Hersey JA. Ordered mixing: a new concept in powder mixing practice. Powder Technol. 1975;11:41–44. doi: 10.1016/0032-5910(75)80021-0. [Cross Ref]
3. Wierik H, Diepenmaat P, Damhuis R. Formulation of lactose for inhaled delivery systems. Pharm. Technol. Eur. 2002;14:47–52.
4. Ganderton D, Kassem NM. Dry powder inhalers. In: Ganderton D, Jones T, editors. Advances in Pharmaceutical Sciences. London, UK: Academic Press; 1992. pp. 165–191.
5. Boer AH, Hagedoorn P, Gjaltema D, Goede J, Kussendrager KD, Frijlink HW. Air classifier technology (ACT) in dry powder inhalation. Part 2. The effect of lactose carrier surface properties on the drug-to-carrier interaction in adhesive mixtures for inhalation. Int J Pharm. 2003;260:201–216. doi: 10.1016/S0378-5173(03)00264-3. [PubMed] [Cross Ref]
6. Podczeck F. The relationship between particulate properties of carrier materials and the adhesion force of drug particles in interactive powder mixtures. J Adhes Sci Technol. 1997;11:1089–1104. doi: 10.1163/156856197X00859. [Cross Ref]
7. Buckton G. Characterization of small changes in the physical properties of powders of significance for dry powder inhaler formulation. Adv Drug Deliv Rev. 1997;26:17–27. doi: 10.1016/S0169-409X(97)00507-3. [PubMed] [Cross Ref]
8. Chan LW, Lim LT, Heng PWS. Immobilization of fine particles on lactose carrier by precision coating and its effect on the performance of dry powder formulations. J Pharm Sci. 2003;92:975–984. doi: 10.1002/jps.10372. [PubMed] [Cross Ref]
9. Kawashima Y, Serigano T, Hino T, Yamamoto H, Takeuchi H. Effect of surface morphology of carrier lactose on dry powder inhalation property of pranlukast hydrate. Int J Pharm. 1998;172:179–188. doi: 10.1016/S0378-5173(98)00202-6. [Cross Ref]
10. Zeng XM, Martin GP, Marriot C, Pritchard J. Lactose as carrier in dry powder formulations: the influence of surface characteristics on drug delivery. J Pharm Sci. 2001;90:1424–1434. doi: 10.1002/jps.1094. [PubMed] [Cross Ref]
11. Zeng XM, Martin GP, Marriot C, Pritchard J. The influence of carrier morphology on drug delivery by dry powder inhalers. Int J Pharm. 2000;200:93–106. doi: 10.1016/S0378-5173(00)00347-1. [PubMed] [Cross Ref]
12. Heng PWS, Chan LW, Lim LT. Quantification of the surface morphologies of lactose carriers and their effect on the in vitro deposition of salbutamol sulphate. Chem Pharm Bull (Tokyo) 2000;48:393–398. [PubMed]
13. Swaminathan V, Kildsig DO. The effect of particle morphology on the physical stability of pharmaceutical powder mixtures: the effect of surface roughness of the carrier on the stability of ordered mixtures. Drug Dev Ind Pharm. 2000;26:365–373. doi: 10.1081/DDC-100101242. [PubMed] [Cross Ref]
14. Podczeck F. The relationship between physical properties of lactose monohydrate and the aerodynamic behaviour of adherent drug particles. Int J Pharm. 1998;160:119–130. doi: 10.1016/S0378-5173(97)00313-X. [Cross Ref]
15. Lord JD, Staniforth JN. Particle size effects on packing and dispersion of powders. In: Dalby RN, Byron PR, Farr SJ, editors. Respiratory Drug Delivery V. Buffalo Grove, IL: Interpharm Press Inc; 2004. pp. 75–84.
16. Zeng XM, Martin GP, Marriot C, Pritchard J. Effect of surface smoothness of lactose on the delivery of salbutamol sulphate from dry powders inhalers. Pharm Res. 1997;14S:136–136.
17. Iida K, Hayakawa Y, Okamoto H, Danjo K, Leuenberger H. Preparation of dry powder inhalation by surface treatment of lactose carrier particles. Chem Pharm Bull (Tokyo) 2003;51:1–5. doi: 10.1248/cpb.51.1. [PubMed] [Cross Ref]
18. Colombo P, Catellani PL, Massimo G, et al. Surface smoothing of lactose particles for dry powder inhalers. In: Dalby RN, Byron PR, Farr SJ, Peart JP, et al., editors. Respiratory Drug Delivery VII. Raleigh, NC: Serentec Press, Inc; 2000. pp. 629–632.
19. Cocconi D, Penotti C, Bettini R, et al. Inhalation mixtures of antiasthmathic drugs with smoothed lactose. In: Dalby RN, Byron PR, Farr SJ, Peart JP, et al., editors. Respiratory Drug Delivery VIII. Richmond, VA: Virginia Commonwealth University; 2002. pp. 739–741.
20. Young PM, Cocconi D, Colombo P, et al. Characterization of a surface modified dry powder inhalation carrier prepared by particle smoothing. J Pharm Pharmacol. 2002;54:1339–1344. doi: 10.1211/002235702760345400. [PubMed] [Cross Ref]
21. Ganderton D. The generation of respirable clouds from coarse powder aggregates. J. Biopharm. Sci. 1992;3:101–105.
22. Price R, Young PM, Edge S, Staniforth JN. The influence of relative humidity on particulate interactions in carrier-based dry powder inhaler formulations. Int J Pharm. 2002;246:47–59. doi: 10.1016/S0378-5173(02)00359-9. [PubMed] [Cross Ref]
23. Chappard D, Degasne I, Huré G, Legrand E, Audran M, Baslé MF. Image analysis measurement of roughness by texture and fractal analysis correlate with contact profilometry. Biomaterials. 2003;24:1399–1407. doi: 10.1016/S0142-9612(02)00524-0. [PubMed] [Cross Ref]
24. Laitinen N, Antikainen O, Yliruusi J. Characterization of particle sizes in bulk pharmaceutical solids using digital image information. AAPS Pharm Sci Tech. 2003;4:E49–E49. doi: 10.1208/pt040449. [PMC free article] [PubMed] [Cross Ref]
25. Brunauer S, Emmett PH, Teller E. Adsorption of gases in multimolecular layers. J Am Chem Soc. 1938;60:309–319. doi: 10.1021/ja01269a023. [Cross Ref]
26. Mullin JW. Crystallization. London, UK: Butterworths & Co Ltd; 1961. pp. 33–35.
27. Nystrom C, Alderborn G, Duberg M, Karehill PG. Bonding surface area and bonding mechanism. Two important factors for the understanding of powder compactability. Drug Dev Ind Pharm. 1993;19:2143–2196. doi: 10.3109/03639049309047189. [Cross Ref]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists