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Adv Pharm Bull. 2019;9(2): 255-261.
doi: 10.15171/apb.2019.029
PMID: 31380251
PMCID: PMC6664120
Scopus ID: 85067238622
  Abstract View: 469
  PDF Download: 347

Research Article

Preparation and Characterization of a Dry Powder Inhaler Composed of PLGA Large Porous Particles Encapsulating Gentamicin Sulfate

Farideh Shiehzadeh 1,2,3 ORCID logo, Mohsen Tafaghodi 3 * ORCID logo, Majid Laal-Dehghani 1,2, Faezeh Mashhoori 1,2, Bibi Sedigheh Fazly Bazzaz 4,5 ORCID logo, Mohsen Imenshahidi 6 ORCID logo

1 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
2 Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
3 Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
4 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
5 Department of Pharmaceutical Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
6 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Purpose: Direct delivery of aminoglycosides to the lungs was under extensive evaluations during the last decades. Because of large particle size, low density and porous structure, large porous particles (LPPs) are versatile carriers for this purpose. In this study, poly (lactic-co-glycolic acid) (PLGA) LPPs encapsulating gentamicin sulfate were prepared and in vitro characteristics of their freeze-dried powder as a dry powder inhaler (DPI) were evaluated.

Methods: To prepare PLGA LPPs, a double emulsification-solvent evaporation method was optimized and gentamicin sulfate was post-loaded in the LPPs. In vitro characteristics including morphological features, thermal behavior, aerodynamic profile and cumulative drug release were evaluated by the scanning electron microscope (SEM), differential scanning calorimetry (DSC), next-generation cascade impactor (NGI) and Franz diffusion cell respectively.

Results: The obtained results revealed that the preparation method was capable to produce spherical large homogenous highly porous particles. 94% of gentamicin sulfate released from LPPs up to 30 minutes. Mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF) were 4.9 µm and 39% respectively.

Conclusion: In this study, dry powder formulation composed of PLGA LPPs encapsulating gentamicin sulfate showed a promising in vitro behavior as a pulmonary delivery carrier. Improvements on the aerodynamic behavior and in vivo evaluations recommended for further developments.

Keywords: Aminoglycosides, Drug delivery systems, Dry powder inhalers, Gentamicin sulfate, Large porous particles, Lung, PLGA
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Submitted: 18 Jan 2019
Revision: 27 Apr 2019
Accepted: 04 May 2019
ePublished: 01 Jun 2019
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