Improving Powder Flow Properties of a Cohesive Lactose Monohydrate Powder by Intensive Mechanical Dry Coating

doi:10.1002/jps.21885

Journal of Pharmaceutical Sciences

Volume 99, Issue 2, February 2010, Pages 969-981

https://doi.org/10.1002/jps.21885 Get rights and content

Abstract

The objective of this study was to improve the cohesive lactose powder flowability. A cohesive lactose monohydrate powder was processed in either a tumbling blender or an intensive mechanical processor with either magnesium stearate or fumed silica. No substantial changes in particle size were detected by laser diffraction following either treatment. The untreated lactose sample exhibited very poor powder flow. Only limited improvements in powder flowability were indicated after the tumbling blending, intensive mechanical processing with the fumed silica or without additives. However, the intensive mechanical processing of the lactose sample with magnesium stearate demonstrated exceptionally large increases in both poured and tapped density as well as notable improvements in all powder flowability indicators examined. Our findings support the use of intensive mechanical processing technique as an effective method to coat cohesive pharmaceutical powders with selected additives, modify the surface nature of the particles, reduce the interparticle cohesive forces and hence improve powder flowability. The subtle differences in powder flow behaviour of lactose samples between the untreated and tumbling blended powders with magnesium stearate were only detected by the powder rheometer using its dynamic mode, indicating its potential advantages over traditional powder flow characterisation approaches. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:969–981, 2010

Section snippets

INTRODUCTION

Particulate handling plays a fundamental part in almost every industrial manufacturing operation.¹ Notably, powder flowability is highly influential and often the major issue with particulate handling and processing. Given this importance, it is perhaps initially surprising that powder flow behaviour remains a relatively poorly understood phenomenon.² Indeed the processing of fine pharmaceutical particulates can be notoriously complex and challenging. As widely observed, powders uniquely

Materials

α-Lactose monohydrate samples (Pharmatose® 450M) were kindly donated by DMV International (Veghel, the Netherlands). Magnesium stearate NF (MgSt) was supplied by Mallinckrodt Baker, Inc. (Phillipsburg, NJ). FS, CAB-O-SIL® M-5, was supplied by Cabot Corporation (Boston, MA), and propan-2-ol from Honeywell Burdick & Jackson (Muskegon, MI). All samples were used as received.

Intensive Mechanical Dry Coating

Processing of lactose samples with MgSt or FS was carried out in a Nobilta-130 unit (Hosokawa Micron Corporation, Osaka,

Scanning Electron Microscopy

Representative SEM micrographs of lactose samples are shown in Figures 2 and 3. For the untreated and mixed batches, fine particles less than 10 µm tended to form agglomerates or be adhered to the surface of larger particles. In contrast, for the mechanofused batches, more particles are present as nonagglomerated primary particles (Fig. 2). At the higher magnification of 3500×, it is quite clear that the untreated batch exhibits flat smooth surfaces and sharp edges (Fig. 3a). For the

DISCUSSION

Laser diffraction particle sizing indicated that no significant changes in particle size distributions of lactose samples were detected after mechanofusion without additives, with MgSt or with FS (Fig. 3). These findings are in agreement with other reports,²⁵, ²⁶ and recently it has been reported that the thickness of coating layer of MgSt after mechanofusion is indicated as less than 10 nm.²⁷ These findings indicate that the coating of MgSt on the surface of lactose particles is too thin to be

CONCLUSIONS

In this study, the flow characteristics of a cohesive lactose monohydrate powder were modified following the processing with MgSt or FS using an intensive mechanical dry-coating technique, termed ‘mechanofusion’. The untreated lactose sample, with primary particle size of around 20 µm, exhibited very poor powder flow which is considered to be unsuitable for pharmaceutical manufacturing operations. After mechanofusion treatment with MgSt, substantial changes in interparticle interactions in the

Acknowledgements

Thanks to Hosokawa Micron Corporation for help in mechanofusion operations. Q.Z. would like to acknowledge the financial support from Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, in the form of faculty scholarship.

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Research ArticlesImproving Powder Flow Properties of a Cohesive Lactose Monohydrate Powder by Intensive Mechanical Dry Coating

Abstract

Section snippets

INTRODUCTION

Materials

Intensive Mechanical Dry Coating

Scanning Electron Microscopy

DISCUSSION

CONCLUSIONS

Acknowledgements

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Research Articles
Improving Powder Flow Properties of a Cohesive Lactose Monohydrate Powder by Intensive Mechanical Dry Coating