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L-Leucine as an excipient against moisture on in vitro aerosolization performances of highly hygroscopic spray-dried powders.
Eur J Pharm Biopharm. 2016 May; 102:132-41.EJ

Abstract

L-Leucine (LL) has been widely used to enhance the dispersion performance of powders for inhalation. LL can also protect powders against moisture, but this effect is much less studied. The aim of this study was to investigate whether LL could prevent moisture-induced deterioration in in vitro aerosolization performances of highly hygroscopic spray-dried powders. Disodium cromoglycate (DSCG) was chosen as a model drug and different amounts of LL (2-40% w/w) were added to the formulation, with the aim to explore the relationship between powder dispersion, moisture protection and physicochemical properties of the powders. The powder formulations were prepared by spray drying of aqueous solutions containing known concentrations of DSCG and LL. The particle sizes were measured by laser diffraction. The physicochemical properties of fine particles were characterized by X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and dynamic vapor sorption (DVS). The surface morphology and chemistry of fine particles were analyzed by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS). In vitro aerosolization performances were evaluated by a next generation impactor (NGI) after the powders were stored at 60% or 75% relative humidity (RH), and 25°C for 24h. Spray-dried (SD) DSCG powders were amorphous and absorbed 30-45% (w/w) water at 70-80% RH, resulting in deterioration in the aerosolization performance of the powders. LL did not decrease the water uptake of DSCG powders, but it could significantly reduce the effect of moisture on aerosolization performances. This is due to enrichment of crystalline LL on the surface of the composite particles. The effect was directly related to the percentage of LL coverage on the surface of particles. Formulations having 61-73% (molar percent) of LL on the particle surface (which correspond to 10-20% (w/w) of LL in the bulk powders) could minimize moisture-induced deterioration in the aerosol performance. In conclusion, particle surface coverage of LL can offer short-term protection against moisture on dispersion of hygroscopic powders.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Li L
Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
Sun S
Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia.
Parumasivam T
Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia.
Denman JA
Future Industries Institute, University of South Australia, Mawson Lakes, South Australia 5095, Australia.
Gengenbach T
CSIRO Manufacturing, Bayview Avenue, Clayton, Victoria 3168, Australia.
Tang P
Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia.
Mao S
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China. Electronic address: maoshirui@syphu.edu.cn.
Chan HK
Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia. Electronic address: kim.chan@sydney.edu.au.

MeSH

Administration, InhalationAerosolsCalorimetry, Differential ScanningChemistry, PharmaceuticalDry Powder InhalersExcipientsHumidityLeucineMicroscopy, Electron, ScanningParticle SizePhotoelectron SpectroscopyPowdersSurface PropertiesWettabilityX-Ray Diffraction

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26970252

Citation

Li, Liang, et al. "L-Leucine as an Excipient Against Moisture On in Vitro Aerosolization Performances of Highly Hygroscopic Spray-dried Powders." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 102, 2016, pp. 132-41.
Li L, Sun S, Parumasivam T, et al. L-Leucine as an excipient against moisture on in vitro aerosolization performances of highly hygroscopic spray-dried powders. Eur J Pharm Biopharm. 2016;102:132-41.
Li, L., Sun, S., Parumasivam, T., Denman, J. A., Gengenbach, T., Tang, P., Mao, S., & Chan, H. K. (2016). L-Leucine as an excipient against moisture on in vitro aerosolization performances of highly hygroscopic spray-dried powders. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 102, 132-41. https://doi.org/10.1016/j.ejpb.2016.02.010
Li L, et al. L-Leucine as an Excipient Against Moisture On in Vitro Aerosolization Performances of Highly Hygroscopic Spray-dried Powders. Eur J Pharm Biopharm. 2016;102:132-41. PubMed PMID: 26970252.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - L-Leucine as an excipient against moisture on in vitro aerosolization performances of highly hygroscopic spray-dried powders. AU - Li,Liang, AU - Sun,Siping, AU - Parumasivam,Thaigarajan, AU - Denman,John A, AU - Gengenbach,Thomas, AU - Tang,Patricia, AU - Mao,Shirui, AU - Chan,Hak-Kim, Y1 - 2016/03/09/ PY - 2015/12/10/received PY - 2016/02/17/revised PY - 2016/02/18/accepted PY - 2016/3/13/entrez PY - 2016/3/13/pubmed PY - 2016/12/17/medline KW - Disodium cromoglycate KW - Dry powder inhalers KW - Fine particle fraction KW - Moisture protection KW - Spray drying KW - l-Leucine SP - 132 EP - 41 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 102 N2 - L-Leucine (LL) has been widely used to enhance the dispersion performance of powders for inhalation. LL can also protect powders against moisture, but this effect is much less studied. The aim of this study was to investigate whether LL could prevent moisture-induced deterioration in in vitro aerosolization performances of highly hygroscopic spray-dried powders. Disodium cromoglycate (DSCG) was chosen as a model drug and different amounts of LL (2-40% w/w) were added to the formulation, with the aim to explore the relationship between powder dispersion, moisture protection and physicochemical properties of the powders. The powder formulations were prepared by spray drying of aqueous solutions containing known concentrations of DSCG and LL. The particle sizes were measured by laser diffraction. The physicochemical properties of fine particles were characterized by X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and dynamic vapor sorption (DVS). The surface morphology and chemistry of fine particles were analyzed by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS). In vitro aerosolization performances were evaluated by a next generation impactor (NGI) after the powders were stored at 60% or 75% relative humidity (RH), and 25°C for 24h. Spray-dried (SD) DSCG powders were amorphous and absorbed 30-45% (w/w) water at 70-80% RH, resulting in deterioration in the aerosolization performance of the powders. LL did not decrease the water uptake of DSCG powders, but it could significantly reduce the effect of moisture on aerosolization performances. This is due to enrichment of crystalline LL on the surface of the composite particles. The effect was directly related to the percentage of LL coverage on the surface of particles. Formulations having 61-73% (molar percent) of LL on the particle surface (which correspond to 10-20% (w/w) of LL in the bulk powders) could minimize moisture-induced deterioration in the aerosol performance. In conclusion, particle surface coverage of LL can offer short-term protection against moisture on dispersion of hygroscopic powders. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/26970252/L_Leucine_as_an_excipient_against_moisture_on_in_vitro_aerosolization_performances_of_highly_hygroscopic_spray_dried_powders_ DB - PRIME DP - Unbound Medicine ER -