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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.
Int J Pharm. 2013 Oct 15; 455(1-2):374-92.IJ

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.

Authors+Show Affiliations

University of Kentucky, College of Pharmacy, Department of Pharmaceutical Sciences, Drug Development Division, Lexington, KY 40536-0596, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23820131

Citation

Park, Chun-Woong, 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, vol. 455, no. 1-2, 2013, pp. 374-92.
Park CW, Li X, Vogt FG, 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. Int J Pharm. 2013;455(1-2):374-92.
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), 374-92. https://doi.org/10.1016/j.ijpharm.2013.06.047
Park CW, 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. Int J Pharm. 2013 Oct 15;455(1-2):374-92. PubMed PMID: 23820131.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Park,Chun-Woong, AU - Li,Xiaojian, AU - Vogt,Frederick G, AU - Hayes,Don,Jr AU - Zwischenberger,Joseph B, AU - Park,Eun-Seok, AU - Mansour,Heidi M, Y1 - 2013/06/29/ PY - 2012/11/29/received PY - 2013/05/14/revised PY - 2013/06/23/accepted PY - 2013/7/4/entrez PY - 2013/7/4/pubmed PY - 2014/3/26/medline KW - Aerosol performance enhancer KW - Antibiotic KW - Controlled release lung delivery KW - Dipalmitoylphosphatidylcholine (DPPC) KW - Particle engineering design KW - Solid-state SP - 374 EP - 92 JF - International journal of pharmaceutics JO - Int J Pharm VL - 455 IS - 1-2 N2 - 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. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/23820131/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(13)00556-5 DB - PRIME DP - Unbound Medicine ER -