Investigations on the Humidity-Induced Transformations of Salbutamol Sulphate Particles Coated with l-Leucine

Janne Raula (Corresponding Author), Frank Thielmann, Jarno Kansikas, Sami Hietala, Minna Annala, Jukka Seppälä, Anna Lähde, Esko I. Kauppinen

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

Purpose: The crystallization and structural integrity of micron-sized inhalable salbutamol sulphate particles coated with l-leucine by different methods are investigated at different humidities. The influence of the l-leucine coating on the crystallization of salbutamol sulphate beneath the coating layer is explored.

Methods: The coated particles are prepared by an aerosol flow reactor method, the formation of the l-leucine coating being controlled by the saturation conditions of the l-leucine. The coating is formed by solute diffusion within a droplet and/or by vapour deposition of l-leucine. The powders are humidified at 0%, 44%, 65% and 75% of relative humidity and the changes in physical properties of the powders are investigated with dynamic vapour sorption analysis (DVS), a differential scanning calorimeter (DSC), and a scanning electron microscope (SEM).

Results: Visual observation show that all the coated particles preserve their structural integrity whereas uncoated salbutamol sulphate particles are unstable at 65% of relative humidity. The coating layer formed by diffusion performs best in terms of its physical stability against moisture and moisture-induced crystallization. The degree of crystallization of salbutamol in the as-prepared powders is within the range 24–35%. The maximum degree of crystallization after drying ranges from 55 to 73% when the salbutamol crystallizes with the aid of moisture. In addition to providing protection against moisture, the l-leucine coating also stabilizes the particle structure against heat at temperatures up to 250°C.

Conclusion: In order to preserve good flowability together with good physical stability, the best coating would contain two l-leucine layers, the inner layer being formed by diffusion (physical stability) and the outer layer by vapour deposition (flowability).
Original languageEnglish
Pages (from-to)2250-2261
JournalPharmaceutical Research
Volume25
Issue number10
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Fingerprint

Albuterol
Humidity
Leucine
Sulfates
Atmospheric humidity
Crystallization
Coatings
Moisture
Powders
Vapor deposition
Structural integrity
Scanning
Aerosols
Calorimeters
Sorption
Drying
Electron microscopes
Physical properties
Hot Temperature
Vapors

Keywords

  • crystallization
  • humidity
  • l-leucine coating
  • salbutamol sulphate
  • stability

Cite this

Raula, J., Thielmann, F., Kansikas, J., Hietala, S., Annala, M., Seppälä, J., ... Kauppinen, E. I. (2008). Investigations on the Humidity-Induced Transformations of Salbutamol Sulphate Particles Coated with l-Leucine. Pharmaceutical Research, 25(10), 2250-2261. https://doi.org/10.1007/s11095-008-9613-4
Raula, Janne ; Thielmann, Frank ; Kansikas, Jarno ; Hietala, Sami ; Annala, Minna ; Seppälä, Jukka ; Lähde, Anna ; Kauppinen, Esko I. / Investigations on the Humidity-Induced Transformations of Salbutamol Sulphate Particles Coated with l-Leucine. In: Pharmaceutical Research. 2008 ; Vol. 25, No. 10. pp. 2250-2261.
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abstract = "Purpose: The crystallization and structural integrity of micron-sized inhalable salbutamol sulphate particles coated with l-leucine by different methods are investigated at different humidities. The influence of the l-leucine coating on the crystallization of salbutamol sulphate beneath the coating layer is explored.Methods: The coated particles are prepared by an aerosol flow reactor method, the formation of the l-leucine coating being controlled by the saturation conditions of the l-leucine. The coating is formed by solute diffusion within a droplet and/or by vapour deposition of l-leucine. The powders are humidified at 0{\%}, 44{\%}, 65{\%} and 75{\%} of relative humidity and the changes in physical properties of the powders are investigated with dynamic vapour sorption analysis (DVS), a differential scanning calorimeter (DSC), and a scanning electron microscope (SEM).Results: Visual observation show that all the coated particles preserve their structural integrity whereas uncoated salbutamol sulphate particles are unstable at 65{\%} of relative humidity. The coating layer formed by diffusion performs best in terms of its physical stability against moisture and moisture-induced crystallization. The degree of crystallization of salbutamol in the as-prepared powders is within the range 24–35{\%}. The maximum degree of crystallization after drying ranges from 55 to 73{\%} when the salbutamol crystallizes with the aid of moisture. In addition to providing protection against moisture, the l-leucine coating also stabilizes the particle structure against heat at temperatures up to 250°C.Conclusion: In order to preserve good flowability together with good physical stability, the best coating would contain two l-leucine layers, the inner layer being formed by diffusion (physical stability) and the outer layer by vapour deposition (flowability).",
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Raula, J, Thielmann, F, Kansikas, J, Hietala, S, Annala, M, Seppälä, J, Lähde, A & Kauppinen, EI 2008, 'Investigations on the Humidity-Induced Transformations of Salbutamol Sulphate Particles Coated with l-Leucine', Pharmaceutical Research, vol. 25, no. 10, pp. 2250-2261. https://doi.org/10.1007/s11095-008-9613-4

Investigations on the Humidity-Induced Transformations of Salbutamol Sulphate Particles Coated with l-Leucine. / Raula, Janne (Corresponding Author); Thielmann, Frank; Kansikas, Jarno; Hietala, Sami; Annala, Minna; Seppälä, Jukka; Lähde, Anna; Kauppinen, Esko I.

In: Pharmaceutical Research, Vol. 25, No. 10, 2008, p. 2250-2261.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Investigations on the Humidity-Induced Transformations of Salbutamol Sulphate Particles Coated with l-Leucine

AU - Raula, Janne

AU - Thielmann, Frank

AU - Kansikas, Jarno

AU - Hietala, Sami

AU - Annala, Minna

AU - Seppälä, Jukka

AU - Lähde, Anna

AU - Kauppinen, Esko I.

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N2 - Purpose: The crystallization and structural integrity of micron-sized inhalable salbutamol sulphate particles coated with l-leucine by different methods are investigated at different humidities. The influence of the l-leucine coating on the crystallization of salbutamol sulphate beneath the coating layer is explored.Methods: The coated particles are prepared by an aerosol flow reactor method, the formation of the l-leucine coating being controlled by the saturation conditions of the l-leucine. The coating is formed by solute diffusion within a droplet and/or by vapour deposition of l-leucine. The powders are humidified at 0%, 44%, 65% and 75% of relative humidity and the changes in physical properties of the powders are investigated with dynamic vapour sorption analysis (DVS), a differential scanning calorimeter (DSC), and a scanning electron microscope (SEM).Results: Visual observation show that all the coated particles preserve their structural integrity whereas uncoated salbutamol sulphate particles are unstable at 65% of relative humidity. The coating layer formed by diffusion performs best in terms of its physical stability against moisture and moisture-induced crystallization. The degree of crystallization of salbutamol in the as-prepared powders is within the range 24–35%. The maximum degree of crystallization after drying ranges from 55 to 73% when the salbutamol crystallizes with the aid of moisture. In addition to providing protection against moisture, the l-leucine coating also stabilizes the particle structure against heat at temperatures up to 250°C.Conclusion: In order to preserve good flowability together with good physical stability, the best coating would contain two l-leucine layers, the inner layer being formed by diffusion (physical stability) and the outer layer by vapour deposition (flowability).

AB - Purpose: The crystallization and structural integrity of micron-sized inhalable salbutamol sulphate particles coated with l-leucine by different methods are investigated at different humidities. The influence of the l-leucine coating on the crystallization of salbutamol sulphate beneath the coating layer is explored.Methods: The coated particles are prepared by an aerosol flow reactor method, the formation of the l-leucine coating being controlled by the saturation conditions of the l-leucine. The coating is formed by solute diffusion within a droplet and/or by vapour deposition of l-leucine. The powders are humidified at 0%, 44%, 65% and 75% of relative humidity and the changes in physical properties of the powders are investigated with dynamic vapour sorption analysis (DVS), a differential scanning calorimeter (DSC), and a scanning electron microscope (SEM).Results: Visual observation show that all the coated particles preserve their structural integrity whereas uncoated salbutamol sulphate particles are unstable at 65% of relative humidity. The coating layer formed by diffusion performs best in terms of its physical stability against moisture and moisture-induced crystallization. The degree of crystallization of salbutamol in the as-prepared powders is within the range 24–35%. The maximum degree of crystallization after drying ranges from 55 to 73% when the salbutamol crystallizes with the aid of moisture. In addition to providing protection against moisture, the l-leucine coating also stabilizes the particle structure against heat at temperatures up to 250°C.Conclusion: In order to preserve good flowability together with good physical stability, the best coating would contain two l-leucine layers, the inner layer being formed by diffusion (physical stability) and the outer layer by vapour deposition (flowability).

KW - crystallization

KW - humidity

KW - l-leucine coating

KW - salbutamol sulphate

KW - stability

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JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

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