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Protection of hydrophobic amino acids against moisture-induced deterioration in the aerosolization performance of highly hygroscopic spray-dried powders.
Eur J Pharm Biopharm. 2017 Oct; 119:224-234.EJ

Abstract

BACKGROUND

Inhalable particles containing amorphous form of drugs or excipients may absorb atmospheric moisture, causing powder aggregation and recrystallization, adversely affecting powder dispersion and lung deposition. The present study aims to explore hydrophobic amino acids for protection against moisture in spray-dried amorphous powders, using disodium cromoglycate (DSCG) as a model drug.

MATERIALS AND METHODS

DSCG powders were produced by co-spray drying with isoleucine (Ile), valine (Val) and methionine (Met) in various concentrations (10, 20 and 40%w/w). Particle size distribution and morphology were measured by laser diffraction and scanning electron microscopy (SEM). Physiochemical properties of the powders were characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and dynamic vapor sorption (DVS). Particle surface chemistry was analyzed by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). In vitro aerosolization performance was evaluated by a next generation impactor (NGI) after the powders were stored at 60% or 75% relative humidity (RH) for one month and three months.

RESULTS AND DISCUSSION

Ile, Val and Met significantly reduced the deleterious effect of moisture on aerosol performance, depending on the amount of amino acids in the formulation. Formulations containing 10% or 20% of Ile, Val and Met showed notable deterioration in aerosol performance, with fine particle fraction (FPF) reduced by 6-15% after one-month storage at both 60% and 75% RH. However, 40% Ile was able to maintain the aerosol performance of DSCG stored at 75% RH for one month, while the FPF dropped by 7.5% after three months of storage. In contrast, 40% Val or Met were able to maintain the aerosol performance at 60% RH storage but not at 75% RH. At 40%w/w ratio, these formulations had particle surface coverage of 94.5% (molar percent) of Ile, 87.1% of Val and 84.6% of Met, respectively, which may explain their moisture protection effects.

CONCLUSION

Ile, Val and Met showed promising moisture protection effect on aerosol performance. The results broaden the understanding on the use of hydrophobic amino acids as an excipient for long-term storage of inhalation powders formulations that are hygroscopic.

Authors+Show Affiliations

Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, New South Wales 2006, Australia.Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, New South Wales 2006, Australia. Electronic address: kim.chan@sydney.edu.au.CSIRO Manufacturing, Bayview Avenue, Clayton, Victoria 3168, Australia.Future Industries Institute, University of South Australia, Mawson Lakes, South Australia 5095, Australia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28655664

Citation

Yu, Jiaqi, et al. "Protection of Hydrophobic Amino Acids Against Moisture-induced Deterioration in the Aerosolization Performance of Highly Hygroscopic Spray-dried Powders." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 119, 2017, pp. 224-234.
Yu J, Chan HK, Gengenbach T, et al. Protection of hydrophobic amino acids against moisture-induced deterioration in the aerosolization performance of highly hygroscopic spray-dried powders. Eur J Pharm Biopharm. 2017;119:224-234.
Yu, J., Chan, H. K., Gengenbach, T., & Denman, J. A. (2017). Protection of hydrophobic amino acids against moisture-induced deterioration in the aerosolization performance of highly hygroscopic spray-dried powders. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 119, 224-234. https://doi.org/10.1016/j.ejpb.2017.06.023
Yu J, et al. Protection of Hydrophobic Amino Acids Against Moisture-induced Deterioration in the Aerosolization Performance of Highly Hygroscopic Spray-dried Powders. Eur J Pharm Biopharm. 2017;119:224-234. PubMed PMID: 28655664.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protection of hydrophobic amino acids against moisture-induced deterioration in the aerosolization performance of highly hygroscopic spray-dried powders. AU - Yu,Jiaqi, AU - Chan,Hak-Kim, AU - Gengenbach,Thomas, AU - Denman,John A, Y1 - 2017/06/24/ PY - 2017/04/18/received PY - 2017/06/22/revised PY - 2017/06/23/accepted PY - 2017/6/29/pubmed PY - 2018/5/5/medline PY - 2017/6/29/entrez KW - Amino acids KW - Disodium cromoglycate (PubChem CID: 27503) KW - Dry powder inhaler (DPI) KW - Moisture protection KW - Spray drying KW - Surface coating KW - dl-Methionine (PubChem CID: 876) KW - l-Isoleucine (PubChem CID: 6306) KW - l-Valine (PubChem CID: 6287) SP - 224 EP - 234 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 119 N2 - BACKGROUND: Inhalable particles containing amorphous form of drugs or excipients may absorb atmospheric moisture, causing powder aggregation and recrystallization, adversely affecting powder dispersion and lung deposition. The present study aims to explore hydrophobic amino acids for protection against moisture in spray-dried amorphous powders, using disodium cromoglycate (DSCG) as a model drug. MATERIALS AND METHODS: DSCG powders were produced by co-spray drying with isoleucine (Ile), valine (Val) and methionine (Met) in various concentrations (10, 20 and 40%w/w). Particle size distribution and morphology were measured by laser diffraction and scanning electron microscopy (SEM). Physiochemical properties of the powders were characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and dynamic vapor sorption (DVS). Particle surface chemistry was analyzed by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). In vitro aerosolization performance was evaluated by a next generation impactor (NGI) after the powders were stored at 60% or 75% relative humidity (RH) for one month and three months. RESULTS AND DISCUSSION: Ile, Val and Met significantly reduced the deleterious effect of moisture on aerosol performance, depending on the amount of amino acids in the formulation. Formulations containing 10% or 20% of Ile, Val and Met showed notable deterioration in aerosol performance, with fine particle fraction (FPF) reduced by 6-15% after one-month storage at both 60% and 75% RH. However, 40% Ile was able to maintain the aerosol performance of DSCG stored at 75% RH for one month, while the FPF dropped by 7.5% after three months of storage. In contrast, 40% Val or Met were able to maintain the aerosol performance at 60% RH storage but not at 75% RH. At 40%w/w ratio, these formulations had particle surface coverage of 94.5% (molar percent) of Ile, 87.1% of Val and 84.6% of Met, respectively, which may explain their moisture protection effects. CONCLUSION: Ile, Val and Met showed promising moisture protection effect on aerosol performance. The results broaden the understanding on the use of hydrophobic amino acids as an excipient for long-term storage of inhalation powders formulations that are hygroscopic. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/28655664/Protection_of_hydrophobic_amino_acids_against_moisture_induced_deterioration_in_the_aerosolization_performance_of_highly_hygroscopic_spray_dried_powders_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(17)30469-1 DB - PRIME DP - Unbound Medicine ER -