Dry Powders for Pulmonary Delivery: Device and Formulation Technologies for an Enhanced Lung Deposition

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 (30 September 2023) | Viewed by 21107

Special Issue Editor

School of Pharmacy and Medical Sciences, University of Bradford, Bradford, UK
Interests: drug delivery to the lung; formulations for dry powder inhalers; formulations for nebulisers; nanosuspension for inhaled
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inhalation aerosol therapy is receiving a lot of interest among researchers as it is the preferred administration route when delivering medication to manage airway diseases and, more recently, systemic diseases.

Lung deposition and, hence, the therapeutic efficiency of DPI depend on several factors, including the formulations, device, and patient inhalation technique. Therefore, it is essential to consider the design of the inhaler device alongside its specific formulation to ensure an enhanced lung deposition and to give the patient the opportunity to achieve maximum therapeutic benefit. Despite advances in current DPI research, there is still a significant gap that needs addressing to understand the relationship of different parameters in the formulation and inhaler device design in enhancing lung deposition and lung bioavailability.

This Special Issue aims to collect the latest advances and state-of-the-art developments in the field of DPI device design, including smart inhalers, contribution of different formulation parameters such as surface energy, cohesion, and adhesion forces and particle engineering technology on lung deposition.

Dr. Khaled Assi
Guest Editor

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Keywords

  • nanodrug delivery system
  • particle engineering technology
  • device development, including smart inhalers
  • dissolution
  • pharmacokinetics and lung bioavailability of inhaled drugs
  • compliance and inhaler technique

Related Special Issue

Published Papers (7 papers)

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Research

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23 pages, 4144 KiB  
Article
Development and Optimisation of Inhalable EGCG Nano-Liposomes as a Potential Treatment for Pulmonary Arterial Hypertension by Implementation of the Design of Experiments Approach
by Fatma Haddad, Nura Mohammed, R. C. Gopalan, Yousef Al Ayoub, Md Talat Nasim and K. H. Assi
Pharmaceutics 2023, 15(2), 539; https://doi.org/10.3390/pharmaceutics15020539 - 06 Feb 2023
Cited by 5 | Viewed by 2555
Abstract
Epigallocatechin gallate (EGCG), the main ingredient in green tea, holds promise as a potential treatment for pulmonary arterial hypertension (PAH). However, EGCG has many drawbacks, including stability issues, low bioavailability, and a short half-life. Therefore, the purpose of this research was to develop [...] Read more.
Epigallocatechin gallate (EGCG), the main ingredient in green tea, holds promise as a potential treatment for pulmonary arterial hypertension (PAH). However, EGCG has many drawbacks, including stability issues, low bioavailability, and a short half-life. Therefore, the purpose of this research was to develop and optimize an inhalable EGCG nano-liposome formulation aiming to overcome EGCG’s drawbacks by applying a design of experiments strategy. The aerodynamic behaviour of the optimum formulation was determined using the next-generation impactor (NGI), and its effects on the TGF-β pathway were determined using a cell-based reporter assay. The newly formulated inhalable EGCG liposome had an average liposome size of 105 nm, a polydispersity index (PDI) of 0.18, a zeta potential of −25.5 mV, an encapsulation efficiency of 90.5%, and a PDI after one month of 0.19. These results are in complete agreement with the predicted values of the model. Its aerodynamic properties were as follows: the mass median aerodynamic diameter (MMAD) was 4.41 µm, the fine particle fraction (FPF) was 53.46%, and the percentage of particles equal to or less than 3 µm was 34.3%. This demonstrates that the novel EGCG liposome has all the properties required to be inhalable, and it is expected to be deposited deeply in the lung. The TGFβ pathway is activated in PAH lungs, and the optimum EGCG nano-liposome inhibits TGFβ signalling in cell-based studies and thus holds promise as a potential treatment for PAH. Full article
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19 pages, 4720 KiB  
Article
Engineering Alginate-Based Dry Powder Microparticles to a Size Suitable for the Direct Pulmonary Delivery of Antibiotics
by Beatriz Arauzo, Álvaro González-Garcinuño, Antonio Tabernero, Javier Calzada-Funes, María Pilar Lobera, Eva M. Martín del Valle and Jesus Santamaria
Pharmaceutics 2022, 14(12), 2763; https://doi.org/10.3390/pharmaceutics14122763 - 09 Dec 2022
Cited by 1 | Viewed by 1476
Abstract
The inhaled route is regarded as one of the most promising strategies as a treatment against pulmonary infections. However, the delivery of drugs in a dry powder form remains challenging. In this work, we have used alginate to form microparticles containing an antibiotic [...] Read more.
The inhaled route is regarded as one of the most promising strategies as a treatment against pulmonary infections. However, the delivery of drugs in a dry powder form remains challenging. In this work, we have used alginate to form microparticles containing an antibiotic model (colistin sulfate). The alginate microparticles were generated by atomization technique, and they were characterized by antimicrobial in vitro studies against Pseudomonas aeruginosa. Optimization of different parameters allowed us to obtain microparticles as a dry powder with a mean size (Feret diameter) of 4.45 ± 1.40 µm and drug loading of 8.5 ± 1.50%. The process developed was able to concentrate most of the colistin deposits on the surface of the microparticles, which could be observed by SEM and a Dual-Beam microscope. This produces a fast in vitro release of the drug, with a 100% release achieved in 4 h. Physicochemical characterization using the FTIR, EDX and PXRD techniques revealed information about the change that occurs from the amorphous to a crystalline form of colistin. Finally, the cytotoxicity of microparticles was tested using lung cell lines (A549 and Calu-3). Results of the study showed that alginate microparticles were able to inhibit bacterial growth while displaying non-toxicity toward lung cells. Full article
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15 pages, 1645 KiB  
Article
Simultaneous Spray Drying for Combination Dry Powder Inhaler Formulations
by Kimberly B. Shepard, Amanda M. Pluntze and David T. Vodak
Pharmaceutics 2022, 14(6), 1130; https://doi.org/10.3390/pharmaceutics14061130 - 26 May 2022
Cited by 5 | Viewed by 3113
Abstract
Spray drying is a particle engineering technique used to manufacture respirable pharmaceutical powders that are suitable for delivery to the deep lung. It is amenable to processing both small molecules and biologic actives, including proteins. In this work, a simultaneous spray-drying process, termed [...] Read more.
Spray drying is a particle engineering technique used to manufacture respirable pharmaceutical powders that are suitable for delivery to the deep lung. It is amenable to processing both small molecules and biologic actives, including proteins. In this work, a simultaneous spray-drying process, termed simul-spray, is described; the process involves two different active pharmaceutical ingredient (API) solutions that are simultaneously atomized through separate nozzles into a single-spray dryer. Collected by a single cyclone, simul-spray produces a uniform mixture of two different active particles in a single-unit operation. While combination therapies for dry powder inhalers containing milled small molecule API are commercially approved, limited options exist for preparing combination treatments that contain both small molecule APIs and biotherapeutic molecules. Simul-spray drying is also ideal for actives which cannot withstand a milling-based particle engineering process, or which require a high dose that is incompatible with a carrier-based formulation. Three combination case studies are demonstrated here, in which bevacizumab is paired with erlotinib, cisplatin, or paclitaxel in a dry powder inhaler formulation. These model systems were chosen for their potential relevance to the local treatment of lung cancer. The resulting formulations preserved the biologic activity of the antibody, achieved target drug concentration, and had aerosol properties suitable for pulmonary delivery. Full article
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28 pages, 5567 KiB  
Article
Rational Development of a Carrier-Free Dry Powder Inhalation Formulation for Respiratory Viral Infections via Quality by Design: A Drug-Drug Cocrystal of Favipiravir and Theophylline
by Si Nga Wong, Jingwen Weng, Ignatius Ip, Ruipeng Chen, Richard Lakerveld, Richard Telford, Nicholas Blagden, Ian J. Scowen and Shing Fung Chow
Pharmaceutics 2022, 14(2), 300; https://doi.org/10.3390/pharmaceutics14020300 - 27 Jan 2022
Cited by 15 | Viewed by 3800
Abstract
Formulating pharmaceutical cocrystals as inhalable dosage forms represents a unique niche in effective management of respiratory infections. Favipiravir, a broad-spectrum antiviral drug with potential pharmacological activity against SARS-CoV-2, exhibits a low aqueous solubility. An ultra-high oral dose is essential, causing low patient compliance. [...] Read more.
Formulating pharmaceutical cocrystals as inhalable dosage forms represents a unique niche in effective management of respiratory infections. Favipiravir, a broad-spectrum antiviral drug with potential pharmacological activity against SARS-CoV-2, exhibits a low aqueous solubility. An ultra-high oral dose is essential, causing low patient compliance. This study reports a Quality-by-Design (QbD)-guided development of a carrier-free inhalable dry powder formulation containing a 1:1 favipiravir–theophylline (FAV-THP) cocrystal via spray drying, which may provide an alternative treatment strategy for individuals with concomitant influenza infections and chronic obstructive pulmonary disease/asthma. The cocrystal formation was confirmed by single crystal X-ray diffraction, powder X-ray diffraction, and the construction of a temperature–composition phase diagram. A three-factor, two-level, full factorial design was employed to produce the optimized formulation and study the impact of critical processing parameters on the resulting median mass aerodynamic diameter (MMAD), fine particle fraction (FPF), and crystallinity of the spray-dried FAV-THP cocrystal. In general, a lower solute concentration and feed pump rate resulted in a smaller MMAD with a higher FPF. The optimized formulation (F1) demonstrated an MMAD of 2.93 μm and an FPF of 79.3%, suitable for deep lung delivery with no in vitro cytotoxicity observed in A549 cells. Full article
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Review

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22 pages, 2419 KiB  
Review
Insights into Asymmetric Liposomes as a Potential Intervention for Drug Delivery Including Pulmonary Nanotherapeutics
by Yaqeen Nadheer Al Badri, Cheng Shu Chaw and Amal Ali Elkordy
Pharmaceutics 2023, 15(1), 294; https://doi.org/10.3390/pharmaceutics15010294 - 15 Jan 2023
Cited by 10 | Viewed by 2635
Abstract
Liposome-based drug delivery systems are nanosized spherical lipid bilayer carriers that can encapsulate a broad range of small drug molecules (hydrophilic and hydrophobic drugs) and large drug molecules (peptides, proteins, and nucleic acids). They have unique characteristics, such as a self-assembling bilayer vesicular [...] Read more.
Liposome-based drug delivery systems are nanosized spherical lipid bilayer carriers that can encapsulate a broad range of small drug molecules (hydrophilic and hydrophobic drugs) and large drug molecules (peptides, proteins, and nucleic acids). They have unique characteristics, such as a self-assembling bilayer vesicular structure. There are several FDA-approved liposomal-based medicines for treatment of cancer, bacterial, and viral infections. Most of the FDA-approved liposomal-based therapies are in the form of conventional “symmetric” liposomes and they are administered mainly by injection. Arikace® is the first and only FDA-approved liposomal-based inhalable therapy (amikacin liposome inhalation suspension) to treat only adults with difficult-to-treat Mycobacterium avium complex (MAC) lung disease as a combinational antibacterial treatment. To date, no “asymmetric liposomes” are yet to be approved, although asymmetric liposomes have many advantages due to the asymmetric distribution of lipids through the liposome’s membrane (which is similar to the biological membranes). There are many challenges for the formulation and stability of asymmetric liposomes. This review will focus on asymmetric liposomes in contrast to conventional liposomes as a potential clinical intervention drug delivery system as well as the formulation techniques available for symmetric and asymmetric liposomes. The review aims to renew the research in liposomal nanovesicle delivery systems with particular emphasis on asymmetric liposomes as future potential carriers for enhancing drug delivery including pulmonary nanotherapeutics. Full article
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22 pages, 29241 KiB  
Review
Progress on Thin Film Freezing Technology for Dry Powder Inhalation Formulations
by Sagar R. Pardeshi, Eknath B. Kole, Harshad S. Kapare, Sachin M. Chandankar, Prashant J. Shinde, Ganesh S. Boisa, Sanjana S. Salgaonkar, Prabhanjan S. Giram, Mahesh P. More, Praveen Kolimi, Dinesh Nyavanandi, Sathish Dyawanapelly and Vijayabhaskarreddy Junnuthula
Pharmaceutics 2022, 14(12), 2632; https://doi.org/10.3390/pharmaceutics14122632 - 28 Nov 2022
Cited by 8 | Viewed by 2772
Abstract
The surface drying process is an important technology in the pharmaceutical, biomedical, and food industries. The final stage of formulation development (i.e., the drying process) faces several challenges, and overall mastering depends on the end step. The advent of new emerging technologies paved [...] Read more.
The surface drying process is an important technology in the pharmaceutical, biomedical, and food industries. The final stage of formulation development (i.e., the drying process) faces several challenges, and overall mastering depends on the end step. The advent of new emerging technologies paved the way for commercialization. Thin film freezing (TFF) is a new emerging freeze-drying technique available for various treatment modalities in drug delivery. TFF has now been used for the commercialization of pharmaceuticals, food, and biopharmaceutical products. The present review highlights the fundamentals of TFF along with modulated techniques used for drying pharmaceuticals and biopharmaceuticals. Furthermore, we have covered various therapeutic applications of TFF technology in the development of nanoformulations, dry powder for inhalations and vaccines. TFF holds promise in delivering therapeutics for lung diseases such as fungal infection, bacterial infection, lung dysfunction, and pneumonia. Full article
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24 pages, 2630 KiB  
Review
Advancements in the Design and Development of Dry Powder Inhalers and Potential Implications for Generic Development
by Abhinav Ram Mohan, Qiang Wang, Sneha Dhapare, Elizabeth Bielski, Anubhav Kaviratna, Liangfeng Han, Susan Boc and Bryan Newman
Pharmaceutics 2022, 14(11), 2495; https://doi.org/10.3390/pharmaceutics14112495 - 17 Nov 2022
Cited by 4 | Viewed by 3508
Abstract
Dry powder inhalers (DPIs) are drug–device combination products where the complexity of the formulation, its interaction with the device, and input from users play important roles in the drug delivery. As the landscape of DPI products advances with new powder formulations and novel [...] Read more.
Dry powder inhalers (DPIs) are drug–device combination products where the complexity of the formulation, its interaction with the device, and input from users play important roles in the drug delivery. As the landscape of DPI products advances with new powder formulations and novel device designs, understanding how these advancements impact performance can aid in developing generics that are therapeutically equivalent to the reference listed drug (RLD) products. This review details the current understanding of the formulation and device related principles driving DPI performance, past and present research efforts to characterize these performance factors, and the implications that advances in formulation and device design may present for evaluating bioequivalence (BE) for generic development. Full article
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