Advanced spray-dried design, physicochemical characterization, and aerosol dispersion performance of vancomycin and clarithromycin multifunctional controlled release particles for targeted respiratory delivery as dry powder inhalation aerosols

Chun Woong Park; Xiaojian Li; Frederick G. Vogt; Don Hayes; Joseph B. Zwischenberger; Eun Seok Park; Heidi M. Mansour

doi:10.1016/j.ijpharm.2013.06.047

Advanced spray-dried design, physicochemical characterization, and aerosol dispersion performance of vancomycin and clarithromycin multifunctional controlled release particles for targeted respiratory delivery as dry powder inhalation aerosols

Chun Woong Park, Xiaojian Li, Frederick G. Vogt, Don Hayes, Joseph B. Zwischenberger, Eun Seok Park, Heidi M. Mansour

Research output: Contribution to journal › Article › peer-review

75 Scopus citations

Abstract

Respirable microparticles/nanoparticles of the antibiotics vancomycin (VCM) and clarithromycin (CLM) were successfully designed and developed by novel organic solution advanced spray drying from methanol solution. Formulation optimization was achieved through statistical experimental design of pump feeding rates of 25% (Low P), 50% (Medium P) and 75% (High P). Systematic and comprehensive physicochemical characterization and imaging were carried out using scanning electron microscopy (SEM), hot-stage microscopy (HSM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Karl Fischer titration (KFT), laser size diffraction (LSD), gravimetric vapor sorption (GVS), confocal Raman microscopy (CRM) and spectroscopy for chemical imaging mapping. These novel spray-dried (SD) microparticulate/nanoparticulate dry powders displayed excellent aerosol dispersion performance as dry powder inhalers (DPIs) with high values in emitted dose (ED), respirable fraction (RF), and fine particle fraction (FPF). VCM DPIs displayed better aerosol dispersion performance compared to CLM DPIs which was related to differences in the physicochemical and particle properties of VCM and CLM. In addition, organic solution advanced co-spray drying particle engineering design was employed to successfully produce co-spray-dried (co-SD) multifunctional microparticulate/ nanoparticulate aerosol powder formulations of VCM and CLM with the essential lung surfactant phospholipid, dipalmitoylphosphatidylcholine (DPPC), for controlled release pulmonary nanomedicine delivery as inhalable dry powder aerosols. Formulation optimization was achieved through statistical experimental design of molar ratios of co-SD VCM:DPPC and co-SD CLM:DPPC. XRPD and DSC confirmed that the phospholipid bilayer structure in the solid-state was preserved following spray drying. Co-SD VCM:DPPC and co-SD CLM:DPPC dry powder aerosols demonstrated controlled release of antibiotic drug that was fitted to various controlled release mathematical fitting models. The Korsmeyer-Peppas model described the best data fit for all powders suggesting super case-II transport mechanism of controlled release. Excellent aerosol dispersion performance for all co-SD microparticulate/nanoparticulate DPIs was higher than the SD antibiotic drugs suggesting that DPPC acts as an aerosol performance enhancer for these antibiotic aerosol dry powders. Co-SD VCM:DPPC DPIs had higher aerosol dispersion parameters compared to co-SD CLM:DPPC which was related to differences in the physicochemical properties of VCM and CLM.

Original language	English
Pages (from-to)	374-392
Number of pages	19
Journal	International Journal of Pharmaceutics
Volume	455
Issue number	1-2
DOIs	https://doi.org/10.1016/j.ijpharm.2013.06.047
State	Published - 2013

Bibliographical note

Funding Information:
The authors gratefully acknowledge financial support from the Sungkyunkwan University for an International Postdoctoral Visiting Scholar Fellowship awarded to Dr. Chun-Woong Park. The authors gratefully acknowledge financial support from the Daniel P. Reedy Quality Achievement Fellowship, the Graduate School Academic Year Fellowship , and the UK Center of Membrane Sciences Fellowship awarded to Xiaojian Li. The authors thank Dr. Dicky Sick Ki Yu for SEM access and Dr. Tonglei Li for XRPD and HSM access.

Funding

The authors gratefully acknowledge financial support from the Sungkyunkwan University for an International Postdoctoral Visiting Scholar Fellowship awarded to Dr. Chun-Woong Park. The authors gratefully acknowledge financial support from the Daniel P. Reedy Quality Achievement Fellowship, the Graduate School Academic Year Fellowship , and the UK Center of Membrane Sciences Fellowship awarded to Xiaojian Li. The authors thank Dr. Dicky Sick Ki Yu for SEM access and Dr. Tonglei Li for XRPD and HSM access.

Funders	Funder number
Graduate School Academic Year Fellowship
Sungkyunkwan University

Keywords

Aerosol performance enhancer
Antibiotic
Controlled release lung delivery
Dipalmitoylphosphatidylcholine (DPPC)
Particle engineering design
Solid-state

ASJC Scopus subject areas

Pharmaceutical Science

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Park, C. W., Li, X., Vogt, F. G., Hayes, D., Zwischenberger, J. B., Park, E. S., & Mansour, H. M. (2013). Advanced spray-dried design, physicochemical characterization, and aerosol dispersion performance of vancomycin and clarithromycin multifunctional controlled release particles for targeted respiratory delivery as dry powder inhalation aerosols. International Journal of Pharmaceutics, 455(1-2), 374-392. https://doi.org/10.1016/j.ijpharm.2013.06.047

Park, Chun Woong ; Li, Xiaojian ; Vogt, Frederick G. et al. / Advanced spray-dried design, physicochemical characterization, and aerosol dispersion performance of vancomycin and clarithromycin multifunctional controlled release particles for targeted respiratory delivery as dry powder inhalation aerosols. In: International Journal of Pharmaceutics. 2013 ; Vol. 455, No. 1-2. pp. 374-392.

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abstract = "Respirable microparticles/nanoparticles of the antibiotics vancomycin (VCM) and clarithromycin (CLM) were successfully designed and developed by novel organic solution advanced spray drying from methanol solution. Formulation optimization was achieved through statistical experimental design of pump feeding rates of 25% (Low P), 50% (Medium P) and 75% (High P). Systematic and comprehensive physicochemical characterization and imaging were carried out using scanning electron microscopy (SEM), hot-stage microscopy (HSM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Karl Fischer titration (KFT), laser size diffraction (LSD), gravimetric vapor sorption (GVS), confocal Raman microscopy (CRM) and spectroscopy for chemical imaging mapping. These novel spray-dried (SD) microparticulate/nanoparticulate dry powders displayed excellent aerosol dispersion performance as dry powder inhalers (DPIs) with high values in emitted dose (ED), respirable fraction (RF), and fine particle fraction (FPF). VCM DPIs displayed better aerosol dispersion performance compared to CLM DPIs which was related to differences in the physicochemical and particle properties of VCM and CLM. In addition, organic solution advanced co-spray drying particle engineering design was employed to successfully produce co-spray-dried (co-SD) multifunctional microparticulate/ nanoparticulate aerosol powder formulations of VCM and CLM with the essential lung surfactant phospholipid, dipalmitoylphosphatidylcholine (DPPC), for controlled release pulmonary nanomedicine delivery as inhalable dry powder aerosols. Formulation optimization was achieved through statistical experimental design of molar ratios of co-SD VCM:DPPC and co-SD CLM:DPPC. XRPD and DSC confirmed that the phospholipid bilayer structure in the solid-state was preserved following spray drying. Co-SD VCM:DPPC and co-SD CLM:DPPC dry powder aerosols demonstrated controlled release of antibiotic drug that was fitted to various controlled release mathematical fitting models. The Korsmeyer-Peppas model described the best data fit for all powders suggesting super case-II transport mechanism of controlled release. Excellent aerosol dispersion performance for all co-SD microparticulate/nanoparticulate DPIs was higher than the SD antibiotic drugs suggesting that DPPC acts as an aerosol performance enhancer for these antibiotic aerosol dry powders. Co-SD VCM:DPPC DPIs had higher aerosol dispersion parameters compared to co-SD CLM:DPPC which was related to differences in the physicochemical properties of VCM and CLM.",

keywords = "Aerosol performance enhancer, Antibiotic, Controlled release lung delivery, Dipalmitoylphosphatidylcholine (DPPC), Particle engineering design, Solid-state",

author = "Park, {Chun Woong} and Xiaojian Li and Vogt, {Frederick G.} and Don Hayes and Zwischenberger, {Joseph B.} and Park, {Eun Seok} and Mansour, {Heidi M.}",

note = "Funding Information: The authors gratefully acknowledge financial support from the Sungkyunkwan University for an International Postdoctoral Visiting Scholar Fellowship awarded to Dr. Chun-Woong Park. The authors gratefully acknowledge financial support from the Daniel P. Reedy Quality Achievement Fellowship, the Graduate School Academic Year Fellowship , and the UK Center of Membrane Sciences Fellowship awarded to Xiaojian Li. The authors thank Dr. Dicky Sick Ki Yu for SEM access and Dr. Tonglei Li for XRPD and HSM access.",

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doi = "10.1016/j.ijpharm.2013.06.047",

language = "English",

volume = "455",

pages = "374--392",

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Park, CW, Li, X, Vogt, FG, Hayes, D, Zwischenberger, JB, Park, ES & Mansour, HM 2013, 'Advanced spray-dried design, physicochemical characterization, and aerosol dispersion performance of vancomycin and clarithromycin multifunctional controlled release particles for targeted respiratory delivery as dry powder inhalation aerosols', International Journal of Pharmaceutics, vol. 455, no. 1-2, pp. 374-392. https://doi.org/10.1016/j.ijpharm.2013.06.047

Advanced spray-dried design, physicochemical characterization, and aerosol dispersion performance of vancomycin and clarithromycin multifunctional controlled release particles for targeted respiratory delivery as dry powder inhalation aerosols. / Park, Chun Woong; Li, Xiaojian; Vogt, Frederick G. et al.
In: International Journal of Pharmaceutics, Vol. 455, No. 1-2, 2013, p. 374-392.

Research output: Contribution to journal › Article › peer-review

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N1 - Funding Information: The authors gratefully acknowledge financial support from the Sungkyunkwan University for an International Postdoctoral Visiting Scholar Fellowship awarded to Dr. Chun-Woong Park. The authors gratefully acknowledge financial support from the Daniel P. Reedy Quality Achievement Fellowship, the Graduate School Academic Year Fellowship , and the UK Center of Membrane Sciences Fellowship awarded to Xiaojian Li. The authors thank Dr. Dicky Sick Ki Yu for SEM access and Dr. Tonglei Li for XRPD and HSM access.

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Park CW, Li X, Vogt FG, Hayes D, Zwischenberger JB, Park ES et al. Advanced spray-dried design, physicochemical characterization, and aerosol dispersion performance of vancomycin and clarithromycin multifunctional controlled release particles for targeted respiratory delivery as dry powder inhalation aerosols. International Journal of Pharmaceutics. 2013;455(1-2):374-392. doi: 10.1016/j.ijpharm.2013.06.047

Advanced spray-dried design, physicochemical characterization, and aerosol dispersion performance of vancomycin and clarithromycin multifunctional controlled release particles for targeted respiratory delivery as dry powder inhalation aerosols

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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