Drug Delivery through Pulmonary

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmaceutical Technology, Manufacturing and Devices".

Deadline for manuscript submissions: closed (10 November 2021) | Viewed by 41894

Special Issue Editors

Department of Electrical and Biological Physics, Institute of Biomaterials, Kwangwoon University, Seoul 01897, Republic of Korea
Interests: biomaterials for biomedical applications; biological safety evaluation of biomaterials including nanomaterials; tissue engineering; photodynamic therapy using nanomaterials; drug delivery using nebulizer
Special Issues, Collections and Topics in MDPI journals
Department of Medical Engineering, Dongguk University College of Medicine, Goyang-si, Gyeonggi-do 10326, Korea
Interests: nebulizer; non-invasive monitoring; photodynamic therapy; biosignal processing; bio-impedance

Special Issue Information

Dear Colleagues,

Recently, drug delivery though the pulmonary has been explored as an alternative method for oral administration, having poor bioavailability to systemic circulation. It has become an attractive method for local and systemic delivery of therapeutic agents in the scientific and biomedical health care area, because the lungs have special properties such as high permeability and a large absorptive surface area, and good blood supply.

For successful pulmonary drug delivery, delivery devices such as a nebulizer and inhaler and formulation of therapeutics agents play an important role. In recent years, significant progress has been made in the development of advanced devices, including a device for powder formulation.

This Special Issue attempts to highlight current research activities in the areas of portable nebulizer or inhaler development for pulmonary drug delivery, formulation development of drugs for nebulizers or inhalers, and advanced delivery methods or tools for some drugs, such as antibiotics, vaccines, exosomes with nucleic acids, peptides, and so on. We invite articles on all aspects of advanced pulmonary drug delivery systems designed with the aim to overcome drug delivery problems.

Prof. Dr. Bong Joo Park
Prof. Dr. Ki chang Nam
Guest Editors

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Keywords

  • drug delivery system
  • pulmonary drug delivery
  • nebulizers
  • inhalers
  • metered-dose inhalers (MDIs)
  • technology for fabrication of nebulizer or inhaler
  • micro/Nanomaterials as a carrier
  • pulmonary imaging
  • in vitro pulmonary delivery models

Published Papers (7 papers)

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Research

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21 pages, 4593 KiB  
Article
Development of High Dose Oseltamivir Phosphate Dry Powder for Inhalation Therapy in Viral Pneumonia
by Shahir Aziz, Regina Scherlieβ and Hartwig Steckel
Pharmaceutics 2020, 12(12), 1154; https://doi.org/10.3390/pharmaceutics12121154 - 27 Nov 2020
Cited by 5 | Viewed by 3263
Abstract
Oseltamivir phosphate (OP) is an antiviral drug available only as oral therapy for the treatment of influenza and as a potential treatment option when in combination with other medication in the fight against the corona virus disease (COVID-19) pneumonia. In this study, OP [...] Read more.
Oseltamivir phosphate (OP) is an antiviral drug available only as oral therapy for the treatment of influenza and as a potential treatment option when in combination with other medication in the fight against the corona virus disease (COVID-19) pneumonia. In this study, OP was formulated as a dry powder for inhalation, which allows drug targeting to the site of action and potentially reduces the dose, aiming a more efficient therapy. Binary formulations were based on micronized excipient particles acting like diluents, which were blended with the drug OP. Different excipient types, excipient ratios, and excipient size distributions were prepared and examined. To investigate the feasibility of delivering high doses of OP in a single dose, 1:1, 1:3, and 3:1 drug/diluent blending ratios have been prepared. Subsequently, the aerosolization performance was evaluated for all prepared formulations by cascade impaction using a novel medium-resistance capsule-based inhaler (UNI-Haler). Formulations with micronized trehalose showed relatively excellent aerosolization performance with highest fine-particle doses in comparison to examined lactose, mannitol, and glucose under similar conditions. Focusing on the trehalose-based dry-powder inhalers’ (DPIs) formulations, a physicochemical characterization of extra micronized grade trehalose in relation to the achieved performance in dispersing OP was performed. Additionally, an early indication of inhaled OP safety on lung cells was noted by the viability MTT assay utilizing Calu-3 cells. Full article
(This article belongs to the Special Issue Drug Delivery through Pulmonary)
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16 pages, 2529 KiB  
Article
Compatible Stability and Aerosol Characteristics of Atrovent® (Ipratropium Bromide) Mixed with Salbutamol Sulfate, Terbutaline Sulfate, Budesonide, and Acetylcysteine
by Yiting Chen, Shilin Du, Zhirui Zhang, Wenxiu He, Enhao Lu, Rui Wang, Xianyi Sha and Yan Ma
Pharmaceutics 2020, 12(8), 776; https://doi.org/10.3390/pharmaceutics12080776 - 15 Aug 2020
Cited by 7 | Viewed by 4800
Abstract
(1) Background: It is common practice in the treatment of respiratory diseases to mix different inhalation solutions for simultaneous inhalation. At present, a small number of studies have been published that evaluate the physicochemical compatibility and aerosol characteristics of different inhalation medications. However, [...] Read more.
(1) Background: It is common practice in the treatment of respiratory diseases to mix different inhalation solutions for simultaneous inhalation. At present, a small number of studies have been published that evaluate the physicochemical compatibility and aerosol characteristics of different inhalation medications. However, none of them studied Atrovent®. Our work aims to address the lack of studies on Atrovent®. (2) Methods: Portions of admixtures were withdrawn at certain time intervals after mixing and were tested by pH determination, osmolarity measurement, and high-performance liquid chromatography (HPLC) assay of each active ingredient as measures of physicochemical compatibility. The geometrical and aerosol particle size distribution, active drug delivery rate, and total active drug delivered were measured to characterize aerosol behaviors. (3) Results: During the testing time, no significant variation was found in the pH value, the osmotic pressure, or the active components of admixtures. With the increase in nebulization volume after mixing, fine particle dose (FPD) and total active drug delivered showed statistically significant improvements, while the active drug delivery rate decreased compared to the single-drug preparations. (4) Conclusions: These results endorse the physicochemical compatibility of Atrovent® over 1 h when mixed with other inhalation medications. Considering aerosol characteristics, simultaneous inhalation is more efficient. Full article
(This article belongs to the Special Issue Drug Delivery through Pulmonary)
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15 pages, 4428 KiB  
Article
The Effect of Particle Size and Surface Roughness of Spray-Dried Bosentan Microparticles on Aerodynamic Performance for Dry Powder Inhalation
by Yong-Bin Kwon, Ji-Hyun Kang, Chang-Soo Han, Dong-Wook Kim and Chun-Woong Park
Pharmaceutics 2020, 12(8), 765; https://doi.org/10.3390/pharmaceutics12080765 - 13 Aug 2020
Cited by 21 | Viewed by 3397
Abstract
The purpose of this study was to prepare spray dried bosentan microparticles for dry powder inhaler and to characterize its physicochemical and aerodynamic properties. The microparticles were prepared from ethanol/water solutions containing bosentan using spray dryer. Three types of formulations (SD60, SD80, and [...] Read more.
The purpose of this study was to prepare spray dried bosentan microparticles for dry powder inhaler and to characterize its physicochemical and aerodynamic properties. The microparticles were prepared from ethanol/water solutions containing bosentan using spray dryer. Three types of formulations (SD60, SD80, and SD100) depending on the various ethanol concentrations (60%, 80%, and 100%, respectively) were used. Bosentan microparticle formulations were characterized by scanning electron microscopy, powder X-ray diffraction, laser diffraction particle sizing, differential scanning calorimetry, Fourier-transform infrared spectroscopy, dissolution test, and in vitro aerodynamic performance using Andersen cascade impactor (ACI) system. In addition, particle image velocimetry (PIV) system was used for directly confirming the actual movement of the aerosolized particles. Bosentan microparticles resulted in formulations with various shapes, surface morphology, and particle size distributions. SD100 was a smooth surface with spherical morphology, SD80 was a rough surfaced with spherical morphology and SD60 was a rough surfaced with corrugated morphology. SD100, SD80, and SD60 showed significantly high drug release up to 1 h compared with raw bosentan. The aerodynamic size of SD80 and SD60 was 1.27 µm and SD100 was 6.95 µm. The microparticles with smaller particle size and a rough surface aerosolized better (%FPF: 63.07 ± 2.39 and 68.27 ± 8.99 for SD60 and SD80, respectively) than larger particle size and smooth surface microparticle (%FPF: 22.64 ± 11.50 for SD100). Full article
(This article belongs to the Special Issue Drug Delivery through Pulmonary)
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14 pages, 1242 KiB  
Article
Aerosol Delivery of Dornase Alfa Generated by Jet and Mesh Nebulizers
by Kyung Hwa Chang, Sang-Hyub Moon, Sun Kook Yoo, Bong Joo Park and Ki Chang Nam
Pharmaceutics 2020, 12(8), 721; https://doi.org/10.3390/pharmaceutics12080721 - 31 Jul 2020
Cited by 11 | Viewed by 3660
Abstract
Recent reports on mesh nebulizers suggest the possibility of stable nebulization of various therapeutic protein drugs. In this study, the in vitro performance and drug stability of jet and mesh nebulizers were examined for dornase alfa and compared with respect to their lung [...] Read more.
Recent reports on mesh nebulizers suggest the possibility of stable nebulization of various therapeutic protein drugs. In this study, the in vitro performance and drug stability of jet and mesh nebulizers were examined for dornase alfa and compared with respect to their lung delivery efficiency in BALB/c mice. We compared four nebulizers: two jet nebulizers (PARI BOY SX with red and blue nozzles), a static mesh nebulizer (NE-U150), and a vibrating mesh nebulizer (NE-SM1). The enzymatic activity of dornase alfa was assessed using a kinetic fluorometric DNase activity assay. Both jet nebulizers had large residual volumes between 24% and 27%, while the volume of the NE-SM1 nebulizer was less than 2%. Evaluation of dornase alfa aerosols produced by the four nebulizers showed no overall loss of enzymatic activity or protein content and no increase in aggregation or degradation. The amount of dornase alfa delivered to the lungs was highest for the PARI BOY SX-red jet nebulizer. This result confirmed that aerosol droplet size is an important factor in determining the efficiency of dornase alfa delivery to the lungs. Further clinical studies and analysis are required before any conclusions can be drawn regarding the clinical safety and efficacy of these nebulizers. Full article
(This article belongs to the Special Issue Drug Delivery through Pulmonary)
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9 pages, 1118 KiB  
Article
Optimal Connection for Tiotropium SMI Delivery through Mechanical Ventilation: An In Vitro Study
by Tien-Pei Fang, Yu-Ju Chen, Tsung-Ming Yang, Szu-Hu Wang, Ming-Szu Hung, Shu-Hua Chiu, Hsin-Hsien Li, James B. Fink and Hui-Ling Lin
Pharmaceutics 2020, 12(3), 291; https://doi.org/10.3390/pharmaceutics12030291 - 24 Mar 2020
Cited by 5 | Viewed by 5099
Abstract
We aimed to quantify Soft Mist Inhalers (SMI) delivery to spontaneous breathing model and compare with different adapters via endotracheal tube during mechanical ventilation or by manual resuscitation. A tiotropium SMI was used with a commercial in-line adapter and a T-adapter placed between [...] Read more.
We aimed to quantify Soft Mist Inhalers (SMI) delivery to spontaneous breathing model and compare with different adapters via endotracheal tube during mechanical ventilation or by manual resuscitation. A tiotropium SMI was used with a commercial in-line adapter and a T-adapter placed between the Y-adapter and the inspiratory limb of the ventilator circuit during mechanical ventilation. The SMI was actuated at the beginning of inspiration and expiration. In separate experiments, a manual resuscitator with T-adapter was attached to endotracheal tube, collecting filter, and a passive test lung. Drug was eluted from collecting filters with salt-based solvent and analyzed using high-performance liquid chromatography. Results showed the percent of SMI label dose inhaled was 3-fold higher with the commercial in-line adapter with actuation during expiration than when synchronized with inspiration. SMI with T-adapter delivery via ventilator was similar to inhalation (1.20%) or exhalation (1.02%), and both had lower delivery dose than with manual resuscitator (2.80%; p = 0.01). The inhaled dose via endotracheal tube was much lower than inhaled dose with spontaneous breathing (22.08%). In conclusion, the inhaled dose with the commercial adapter was higher with SMI actuated during expiration, but still far less than reported spontaneous inhaled dose. Full article
(This article belongs to the Special Issue Drug Delivery through Pulmonary)
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11 pages, 2469 KiB  
Article
Aerosol Characteristics and Physico-Chemical Compatibility of Combivent® (Containing Salbutamol and Ipratropium Bromide) Mixed with Three Other Inhalants: Budesonide, Beclomethasone or N-Acetylcysteine
by Rui Zhang, Junhua Hu, Liangjun Deng, Sha Li, Xi Chen, Fei Liu, Shanping Wang, Khaja Shameem Mohammed Abdul, Huimin Beng and Wen Tan
Pharmaceutics 2020, 12(1), 78; https://doi.org/10.3390/pharmaceutics12010078 - 17 Jan 2020
Cited by 7 | Viewed by 4485
Abstract
Inhalation therapy with a nebulizer is widely used in chronic respiratory disease. Mixing inhalation solutions/suspensions for simultaneous inhalation is more convenient and might simplify the administration procedure. However, there are no data available to address the in vitro aerosol characteristics and physico-chemical compatibility [...] Read more.
Inhalation therapy with a nebulizer is widely used in chronic respiratory disease. Mixing inhalation solutions/suspensions for simultaneous inhalation is more convenient and might simplify the administration procedure. However, there are no data available to address the in vitro aerosol characteristics and physico-chemical compatibility of Combivent® (containing Salbutamol and Ipratropium bromide) with other inhalation solutions/suspensions. In order to investigate the in vitro aerosol characteristics and physico-chemical compatibility of Combivent® with Budesonide, Beclomethasone, and N-acetylcysteine, the appearance, pH, osmotic pressure, chemical stability, mass median aerodynamic diameter (MMAD), fine particles fraction (FPF), particle size corresponding to X50 (particle size, which accounts for 50% of the total cumulative percentage of volume of all particles), delivery rate, and total delivery of the mixed inhalation solution/suspension were tested. There was no change in the appearance such as a change in color or precipitation formation at room temperature. The pH, osmolality, and chemicals of the mixtures were stable for 24 h after mixing. There were no significant differences between Combivent®, Budesonide, Beclomethasone, N-acetylcysteine, and the mixtures in MMAD, FPF, X50, the delivery rate, and the total delivery. This indicates that the mixtures were physically and chemically compatible. The mixing did not influence the particle size, distribution, or delivery compatibility of the mixtures. Full article
(This article belongs to the Special Issue Drug Delivery through Pulmonary)
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Review

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28 pages, 14776 KiB  
Review
Dry Powder for Pulmonary Delivery: A Comprehensive Review
by Birendra Chaurasiya and You-Yang Zhao
Pharmaceutics 2021, 13(1), 31; https://doi.org/10.3390/pharmaceutics13010031 - 28 Dec 2020
Cited by 94 | Viewed by 16424
Abstract
The pulmonary route has long been used for drug administration for both local and systemic treatment. It possesses several advantages, which can be categorized into physiological, i.e., large surface area, thin epithelial membrane, highly vascularized, limited enzymatic activity, and patient convenience, i.e., non-invasive, [...] Read more.
The pulmonary route has long been used for drug administration for both local and systemic treatment. It possesses several advantages, which can be categorized into physiological, i.e., large surface area, thin epithelial membrane, highly vascularized, limited enzymatic activity, and patient convenience, i.e., non-invasive, self-administration over oral and systemic routes of drug administration. However, the formulation of dry powder for pulmonary delivery is often challenging due to restrictions on aerodynamic size and the lung’s lower tolerance capacity in comparison with an oral route of drug administration. Various physicochemical properties of dry powder play a major role in the aerosolization, deposition, and clearance along the respiratory tract. To prepare suitable particles with optimal physicochemical properties for inhalation, various manufacturing methods have been established. The most frequently used industrial methods are milling and spray-drying, while several other alternative methods such as spray-freeze-drying, supercritical fluid, non-wetting templates, inkjet-printing, thin-film freezing, and hot-melt extrusion methods are also utilized. The aim of this review is to provide an overview of the respiratory tract structure, particle deposition patterns, and possible drug-clearance mechanisms from the lungs. This review also includes the physicochemical properties of dry powder, various techniques used for the preparation of dry powders, and factors affecting the clinical efficacy, as well as various challenges that need to be addressed in the future. Full article
(This article belongs to the Special Issue Drug Delivery through Pulmonary)
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