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Correlations between surface composition and aerosolization of jet-milled dry powder inhaler formulations with pharmaceutical lubricants.
Int J Pharm. 2019 Sep 10; 568:118504.IJ

Abstract

Co-jet-milling drugs and lubricants may enable simultaneous particle size reduction and surface coating to achieve satisfactory aerosolization performance. This study aims to establish the relationship between surface lubricant coverage and aerosolization behavior of a model drug (ciprofloxacin HCl) co-jet-milled with lubricants [magnesium stearate (MgSt) or l-leucine]. The co-jet-milled formulations were characterized for particle size, morphology, cohesion, Carr's index, and aerosolization performance. The surface lubricant coating was assessed by probing surface chemical composition using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary-ion mass spectrometry (ToF-SIMS). The effects of co-jet-milling on the surface energy and in vitro dissolution of ciprofloxacin were also evaluated. Our results indicated that, in general, the ciprofloxacin co-jet-milled with l-leucine at >0.5% w/w showed a significant higher fine particle fraction (FPF) compared with the ciprofloxacin jet-milled alone. The FPF values plateau at or above 5% w/w for both MgSt and l-leucine. We have established the quantitative correlations between surface lubricant coverage and aerosolization in the tested range for each of the lubricants. More importantly, our results suggest different mechanisms to improve aerosolization for MgSt-coating and l-leucine-coating, respectively: MgSt-coating reduces inter-particulate interactions through the formation of low surface energy coating films, while l-leucine-coating not only reduces the surface energy but also creates rough particle surfaces that reduce inter-particulate contact area. Furthermore, surface coatings with 5% w/w MgSt (which is hydrophobic) did not lead to substantial changes in in vitro dissolution. Our findings have shown that the coating structure/quality and their effects could be highly dependent on the process and the coating material. The findings from this mechanistic study provide fundamental understanding of the critical effects of MgSt and l-leucine surface coverages on aerosolization and powder flow properties of inhalation particles.

Authors+Show Affiliations

Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.Future Industries Institute, University of South Australia, Mawson Lakes, SA 5095, Australia.Birck Nanotechnology Center, Purdue University, West Lafayette, IN 47907, USA.Inhalation Product Development, Pharmaceutical Technology & Development, AstraZeneca, Gothenburg, Sweden.Small Molecule Pharmaceutics Department, Genentech, Inc., One DNA Way, South San Francisco, CA 94080, USA.Inhalation Product Development, Pharmaceutical Technology & Development, AstraZeneca, Gothenburg, Sweden.Small Molecule Pharmaceutics Department, Genentech, Inc., One DNA Way, South San Francisco, CA 94080, USA.Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA. Electronic address: tonyzhou@purdue.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31299339

Citation

Mangal, Sharad, et al. "Correlations Between Surface Composition and Aerosolization of Jet-milled Dry Powder Inhaler Formulations With Pharmaceutical Lubricants." International Journal of Pharmaceutics, vol. 568, 2019, p. 118504.
Mangal S, Park H, Nour R, et al. Correlations between surface composition and aerosolization of jet-milled dry powder inhaler formulations with pharmaceutical lubricants. Int J Pharm. 2019;568:118504.
Mangal, S., Park, H., Nour, R., Shetty, N., Cavallaro, A., Zemlyanov, D., Thalberg, K., Puri, V., Nicholas, M., Narang, A. S., & Zhou, Q. T. (2019). Correlations between surface composition and aerosolization of jet-milled dry powder inhaler formulations with pharmaceutical lubricants. International Journal of Pharmaceutics, 568, 118504. https://doi.org/10.1016/j.ijpharm.2019.118504
Mangal S, et al. Correlations Between Surface Composition and Aerosolization of Jet-milled Dry Powder Inhaler Formulations With Pharmaceutical Lubricants. Int J Pharm. 2019 Sep 10;568:118504. PubMed PMID: 31299339.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Correlations between surface composition and aerosolization of jet-milled dry powder inhaler formulations with pharmaceutical lubricants. AU - Mangal,Sharad, AU - Park,Heejun, AU - Nour,Reham, AU - Shetty,Nivedita, AU - Cavallaro,Alex, AU - Zemlyanov,Dmitry, AU - Thalberg,Kyrre, AU - Puri,Vibha, AU - Nicholas,Mark, AU - Narang,Ajit S, AU - Zhou,Qi Tony, Y1 - 2019/07/09/ PY - 2019/04/20/received PY - 2019/07/03/revised PY - 2019/07/07/accepted PY - 2019/7/13/pubmed PY - 2020/1/25/medline PY - 2019/7/13/entrez KW - Aerosol performance KW - Dry powder inhaler KW - High-dose KW - Jet-milling KW - Lubricant KW - Surface composition SP - 118504 EP - 118504 JF - International journal of pharmaceutics JO - Int J Pharm VL - 568 N2 - Co-jet-milling drugs and lubricants may enable simultaneous particle size reduction and surface coating to achieve satisfactory aerosolization performance. This study aims to establish the relationship between surface lubricant coverage and aerosolization behavior of a model drug (ciprofloxacin HCl) co-jet-milled with lubricants [magnesium stearate (MgSt) or l-leucine]. The co-jet-milled formulations were characterized for particle size, morphology, cohesion, Carr's index, and aerosolization performance. The surface lubricant coating was assessed by probing surface chemical composition using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary-ion mass spectrometry (ToF-SIMS). The effects of co-jet-milling on the surface energy and in vitro dissolution of ciprofloxacin were also evaluated. Our results indicated that, in general, the ciprofloxacin co-jet-milled with l-leucine at >0.5% w/w showed a significant higher fine particle fraction (FPF) compared with the ciprofloxacin jet-milled alone. The FPF values plateau at or above 5% w/w for both MgSt and l-leucine. We have established the quantitative correlations between surface lubricant coverage and aerosolization in the tested range for each of the lubricants. More importantly, our results suggest different mechanisms to improve aerosolization for MgSt-coating and l-leucine-coating, respectively: MgSt-coating reduces inter-particulate interactions through the formation of low surface energy coating films, while l-leucine-coating not only reduces the surface energy but also creates rough particle surfaces that reduce inter-particulate contact area. Furthermore, surface coatings with 5% w/w MgSt (which is hydrophobic) did not lead to substantial changes in in vitro dissolution. Our findings have shown that the coating structure/quality and their effects could be highly dependent on the process and the coating material. The findings from this mechanistic study provide fundamental understanding of the critical effects of MgSt and l-leucine surface coverages on aerosolization and powder flow properties of inhalation particles. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/31299339/Correlations_between_surface_composition_and_aerosolization_of_jet_milled_dry_powder_inhaler_formulations_with_pharmaceutical_lubricants_ DB - PRIME DP - Unbound Medicine ER -