l -Leucine as an excipient against moisture on in vitro aerosolization performances of highly hygroscopic spray-dried powders
| Autor: | Liang Li, Thaigarajan Parumasivam, Thomas R. Gengenbach, Patricia Tang, Siping Sun, Shirui Mao, Hak-Kim Chan, John A. Denman |
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| Přispěvatelé: | Li, Liang, Sun, Siping, Parumasivam, Thaigarajan, Denman, John A, Gengenbach, Thomas, Tang, Patricia, Mao, Shirui, Chan, Hak-Kim |
| Rok vydání: | 2016 |
| Předmět: |
Thermogravimetric analysis
Materials science Surface Properties L-Leucine Chemistry Pharmaceutical Pharmaceutical Science Mineralogy 02 engineering and technology 030226 pharmacology & pharmacy Excipients moisture protection 03 medical and health sciences 0302 clinical medicine Differential scanning calorimetry X-Ray Diffraction Leucine Administration Inhalation spray drying Particle Size Aerosolization Aerosols Calorimetry Differential Scanning Moisture Photoelectron Spectroscopy dry powder inhalers Dry Powder Inhalers Humidity General Medicine 021001 nanoscience & nanotechnology Spray drying Microscopy Electron Scanning Wettability Particle fine particle fraction Dynamic vapor sorption Particle size Powders 0210 nano-technology disodium cromoglycate Biotechnology Nuclear chemistry |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 102:132-141 |
| ISSN: | 0939-6411 |
| DOI: | 10.1016/j.ejpb.2016.02.010 |
| Popis: | 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 degrees C for 24 h. 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 Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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