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Disintegration of Weak Agglomerates
Principal Investigator: Prof. M. Ghadiri

Co-Investigator(s): Dr R. Boerefijn and Dr Z. Ning

Sponsor(s): Glaxo-Wellcome

Status: Completed (1997)

Abstract

Inhalation is a convenient and potentially attractive method of drug delivery for a number of important illnesses, not only those affecting the respiratory system such as asthma, but also for a variety of other illnesses for which other methods of drug delivery are problematic such as diabetes. In this method of delivery the drug particles, in sizes appropriate for deep penetration into the lungs, have to be dispersed into an air stream for inhalation.

In a new development of inhalers known as dry powder inhalers the drug particles are prepared in the form of an agglomerate, either on their own or mounted on an excipient suitable fordispensing. The agglomerates are then disintegrated by impact on a target and dispersed in air for inhalation. The precise dosing and disintegration of the agglomerates is essential for the success and effectiveness of dry powder inhalation.

The disintegration of the agglomerates depends on the bonding mechanism and on the agglomerate structure, both of which are under investigation in this work. Lactose, the material used in this study, is commonly used in the pharmaceutical industry as an excipient. The specific effects of impact velocity and ambient humidity level on the extent and mechanism of disintegration are elucidated using a single agglomerate impact test. The agglomerates are shown to fail in a mode similar to the ductile failure mode for a solid material,with large overall deformation and shear, without the development of a clear crack plane.

Figure 1. Agglomerate impact at 10 m s-1 (time relative to contact time).

Figure 2. Lactose agglomerate.

Figure 3. Agglomerate simulated by Distinct Element Analysis before impact.

Figure 4. Simulation of an impact of an agglomerate at 10.0 m s-1.

Colour coding
. white - singlets
. yellow - clusters containing 2 - 10 particles
. cyan clusters containing 11 - 30 particles
. pink clusters containing 31 - 100 particles
. blue - residual cluster

Publications

Boerefijn, R., Ning, Z. and Ghadiri, M., (1997) Impact breakage of weak lactose agglomerates. Proc. First European Congress on Chemical Engineering, Florence (It.), 4-7 May. 2: 883-886.

Ning, Z., Boerefijn, R. and Ghadiri, M., (1997) Computer-aided design of agglomerates and strength analysis upon impact. Proc. 1997 IChemE Research Event, Nottingham/ Loughborough, 7-9 April, pp. 445-448.

Ning, Z., Boerefijn, R., Ghadiri, M. and Thornton, C., (1997) Distinct element simulation of impact breakage of lactose agglomerates. Adv. Powder Technol., 8 (1): 1-23.

Ning, Z., Boerefijn, R., Ghadiri, M. and Thornton, C., (1997) Impact of weak agglomerates and effects of particle size and bond strength distribution. In Powders and Grains '97, R. P. Behringer and J. T. Jenkins eds, A.A. Balkema, Rotterdam, pp. 127-130.





	Disintegration of Weak Agglomerates Principal Investigator: Prof. M. Ghadiri Co-Investigator(s): Dr R. Boerefijn and Dr Z. Ning Sponsor(s): Glaxo-Wellcome Status: Completed (1997) Abstract Inhalation is a convenient and potentially attractive method of drug delivery for a number of important illnesses, not only those affecting the respiratory system such as asthma, but also for a variety of other illnesses for which other methods of drug delivery are problematic such as diabetes. In this method of delivery the drug particles, in sizes appropriate for deep penetration into the lungs, have to be dispersed into an air stream for inhalation. In a new development of inhalers known as dry powder inhalers the drug particles are prepared in the form of an agglomerate, either on their own or mounted on an excipient suitable fordispensing. The agglomerates are then disintegrated by impact on a target and dispersed in air for inhalation. The precise dosing and disintegration of the agglomerates is essential for the success and effectiveness of dry powder inhalation. The disintegration of the agglomerates depends on the bonding mechanism and on the agglomerate structure, both of which are under investigation in this work. Lactose, the material used in this study, is commonly used in the pharmaceutical industry as an excipient. The specific effects of impact velocity and ambient humidity level on the extent and mechanism of disintegration are elucidated using a single agglomerate impact test. The agglomerates are shown to fail in a mode similar to the ductile failure mode for a solid material,with large overall deformation and shear, without the development of a clear crack plane. Figure 1. Agglomerate impact at 10 m s-1 (time relative to contact time). Figure 2. Lactose agglomerate. Figure 3. Agglomerate simulated by Distinct Element Analysis before impact. Figure 4. Simulation of an impact of an agglomerate at 10.0 m s-1. Colour coding . white - singlets . yellow - clusters containing 2 - 10 particles . cyan clusters containing 11 - 30 particles . pink clusters containing 31 - 100 particles . blue - residual cluster Publications Boerefijn, R., Ning, Z. and Ghadiri, M., (1997) Impact breakage of weak lactose agglomerates. Proc. First European Congress on Chemical Engineering, Florence (It.), 4-7 May. 2: 883-886. Ning, Z., Boerefijn, R. and Ghadiri, M., (1997) Computer-aided design of agglomerates and strength analysis upon impact. Proc. 1997 IChemE Research Event, Nottingham/ Loughborough, 7-9 April, pp. 445-448. Ning, Z., Boerefijn, R., Ghadiri, M. and Thornton, C., (1997) Distinct element simulation of impact breakage of lactose agglomerates. Adv. Powder Technol., 8 (1): 1-23. Ning, Z., Boerefijn, R., Ghadiri, M. and Thornton, C., (1997) Impact of weak agglomerates and effects of particle size and bond strength distribution. In Powders and Grains '97, R. P. Behringer and J. T. Jenkins eds, A.A. Balkema, Rotterdam, pp. 127-130.