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A comment on "Ability of using different dry powder inhalers during COPD exacerbations"

Muneswarao J, Hassali MA, Verma AK

Pulm Pharmacol Ther, 2018 04;49:60.
PMID: 29309890 DOI: 10.1016/j.pupt.2018.01.001
Matched MeSH terms: Dry Powder Inhalers*
Effect of storage temperature on the stability of spray dried bacteriophage powders

Leung SSY, Parumasivam T, Nguyen A, Gengenbach T, Carter EA, Carrigy NB, et al.

Eur J Pharm Biopharm, 2018 Jun;127:213-222.
PMID: 29486303 DOI: 10.1016/j.ejpb.2018.02.033

This study aimed to assess the robustness of using a spray drying approach and formulation design in producing inhalable phage powders. Two types of Pseudomonas phages, PEV2 (Podovirus) and PEV40 (Myovirus) in two formulations containing different amounts of trehalose (70% and 60%) and leucine (30% and 40%) were studied. Most of the surface of the produced powders was found to be covered in crystalline leucine. The powders were stored at 4 °C and 20 °C under vacuum. The phage stability and in vitro aerosol performance of the phage powders were examined on the day of production and after 1, 3 and 12 months of storage. A minor titer loss during production was observed for both phages (0.2-0.8 log10 pfu/ml). The storage stability of the produced phage powders was found to be phage and formulation dependent. No further reduction in titer occurred for PEV2 powders stored at 4 °C across the study. The formulation containing 30% leucine maintained the viability of PEV2 at 20 °C, while the formulation containing 40% leucine gradually lost titer over time with a storage reduction of ∼0.9 log10 pfu/ml measured after 12 months. In comparison, the PEV40 phage powders generally had a ∼ 0.5 log10 pfu/ml loss upon storage regardless of temperature. When aerosolized, the total in vitro lung doses of PEV2 were of the order of 107 pfu, except the formulation containing 40% leucine stored at 20 °C which had a lower lung dose. The PEV40 powders also had lung doses of 106-107 pfu. The results demonstrate that spray dried Myoviridae and Podoviridae phage in a simple formulation of leucine and trehalose can be successfully stored for one year at 4 °C and 20 °C with vacuum packaging.

Matched MeSH terms: Dry Powder Inhalers/methods
Fulltext Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis

Alhajj N, Yahya MFZR, O'Reilly NJ, Cathcart H

Eur J Pharm Sci, 2024 Jan 01;192:106654.
PMID: 38013123 DOI: 10.1016/j.ejps.2023.106654

Cystic fibrosis (CF) is an inherited lung disease characterised by the accumulation of thick layers of dried mucus in the lungs which serve as a nidus for chronic infection. Pseudomonas aeruginosa is the predominant cause of chronic lung infection in cystic fibrosis. The dense mucus coupled with biofilm formation hinder antibiotic penetration and prevent them from reaching their target. Mucoactive agents are recommended in the treatment of CF in combination with antibiotics. In spite of the extensive research in developing novel drug combinations for the treatment of lung infection in CF, to our knowledge, there is no study that combines antibiotic, antibiofilm and mucoactive agent in a single inhaled dry powder formulation. In the present study, we investigate the possibility of adding a mucoactive agent to our previously developed ciprofloxacinquercetin (antibiotic-antibiofilm) dry powder for inhalation. Three mucoactive agents, namely mannitol (MAN), N-acetyl-L-cysteine (NAC) and ambroxol hydrochloride (AMB), were investigated for this purpose. The ternary combinations were prepared via spray drying without the addition of excipients. All ternary combinations conserved or improved the antibacterial and biofilm inhibition activities of ciprofloxacin against P. aeruginosa (ATCC 10145). The addition of AMB resulted in an amorphous ternary combination (SD-CQA) with superior physical stability as indicated by DSC and nonambient XRPD. Furthermore, SD-CQA displayed better in vitro aerosolization performance (ED ∼ 71 %; FPF ∼ 49 %) compared to formulations containing MAN and NAC (ED ∼ 64 % and 44 %; FPF ∼ 44 % and 29 %, respectively). In conclusion, a ternary drug combination powder with suitable aerosolization, physical stability and antibacterial/antibiofilm properties was prepared by a single spray drying step.

Matched MeSH terms: Dry Powder Inhalers/methods
Fulltext Critical physicochemical attributes of chitosan nanoparticles admixed lactose-PEG 3000 microparticles in pulmonary inhalation

Alhajj N, Zakaria Z, Naharudin I, Ahsan F, Li W, Wong TW

Asian J Pharm Sci, 2020 May;15(3):374-384.
PMID: 32636955 DOI: 10.1016/j.ajps.2019.02.001

Chitosan nanoparticles are exhalation prone and agglomerative to pulmonary inhalation. Blending nanoparticles with lactose microparticles (∼5 µm) could mutually reduce their agglomeration through surface adsorption phenomenon. The chitosan nanoparticles of varying size, size distribution, zeta potential, crystallinity, shape and surface roughness were prepared by spray drying technique as a function of chitosan, surfactant and processing conditions. Lactose-polyethylene glycol 3000 (PEG3000) microparticles were similarly prepared. The chitosan nanoparticles, physically blended with fine lactose-PEG3000 microparticles, exhibited a comparable inhalation performance with the commercial dry powder inhaler products (fine particle fraction between 20% and 30%). Cascade impactor analysis indicated that the aerosolization and inhalation performance of chitosan nanoparticles was promoted by their higher zeta potential and circularity, and larger size attributes of which led to reduced inter-nanoparticulate aggregation and favored nanoparticles interacting with lactose-PEG3000 micropaticles that aided their delivery into deep and peripheral lungs.

Matched MeSH terms: Dry Powder Inhalers
Critical Parameters for Particle-Based Pulmonary Delivery of Chemotherapeutics

Dabbagh A, Abu Kasim NH, Yeong CH, Wong TW, Abdul Rahman N

J Aerosol Med Pulm Drug Deliv, 2018 06;31(3):139-154.
PMID: 29022837 DOI: 10.1089/jamp.2017.1382

Targeted delivery of chemotherapeutics through the respiratory system is a potential approach to improve drug accumulation in the lung tumor, while decreasing their negative side effects. However, elimination by the pulmonary clearance mechanisms, including the mucociliary transport system, and ingestion by the alveolar macrophages, rapid absorption into the blood, enzymatic degradation, and low control over the deposition rate and location remain the main complications for achieving an effective pulmonary drug delivery. Therefore, particle-based delivery systems have emerged to minimize pulmonary clearance mechanisms, enhance drug therapeutic efficacy, and control the release behavior. A successful implementation of a particle-based delivery system requires understanding the influential parameters in terms of drug carrier, inhalation technology, and health status of the patient's respiratory system. This review aims at investigating the parameters that significantly drive the clinical outcomes of various particle-based pulmonary delivery systems. This should aid clinicians in appropriate selection of a delivery system according to their clinical setting. It will also guide researchers in addressing the remaining challenges that need to be overcome to enhance the efficiency of current pulmonary delivery systems for aerosols.

Matched MeSH terms: Dry Powder Inhalers
Inhalable solid lipid nanoparticles of levofloxacin for potential tuberculosis treatment

Paul PK, Nakpheng T, Paliwal H, Prem Ananth K, Srichana T

Int J Pharm, 2024 Jul 20;660:124309.
PMID: 38848797 DOI: 10.1016/j.ijpharm.2024.124309

Delivering novel antimycobacterial agents through the pulmonary route using nanoparticle-based systems shows promise for treating diseases like tuberculosis. However, creating dry powder inhaler (DPI) with suitable aerodynamic characteristics while preserving nanostructure integrity and maintaining bioactivity until the active ingredient travels deeply into the lungs is a difficult challenge. We developed DPI formulations containing levofloxacin-loaded solid lipid nanoparticles (SLNs) via spray-drying technique with tailored aerosolization characteristics for effective inhalation therapy. A range of biophysical techniques, including transmission electron microscopy, confocal microscopy, and scanning electron microscopy were used to measure the morphologies and sizes of the spray-dried microparticles that explored both the geometric and aerodynamic properties. Spray drying substantially reduced the particle sizes of the SLNs while preserving their nanostructural integrity and enhancing aerosol dispersion with efficient mucus penetration. Despite a slower uptake rate compared to plain SLNs, the polyethylene glycol modified formulations exhibited enhanced cellular uptake in both A549 and NR8383 cell lines. The percent viability of Mycobacterium bovis had dropped to nearly 0 % by day 5 for both types of SLNs. Interestingly, the levofloxacin-loaded SLNs demonstrated a lower minimum bactericidal concentration (0.25 µg/mL) compared with pure levofloxacin (1 µg/mL), which indicated the formulations have potential as effective treatments for tuberculosis.

Matched MeSH terms: Dry Powder Inhalers*
Can patients achieve sufficient peak inspiratory flow rate (PIFR) with Turbuhaler® during acute exacerbation of asthma?

Mohd Rhazi NA, Muneswarao J, Abdul Aziz F, Ibrahim B, Kamalludin A, Soelar SA

J Asthma, 2023 Aug;60(8):1608-1612.
PMID: 36650693 DOI: 10.1080/02770903.2023.2169930

INTRODUCTION: Anti-inflammatory reliever (AIR) with or without regular maintenance delivered through Turbuhaler® has been widely recommended in the GINA strategy document. These patients are not prescribed with additional reliever inhalers, but dependent on Turbuhaler® during acute asthma episodes. The peak inspiratory flow rate (PIFR) is crucial in drug delivery from a dry powder inhaler (DPI) such as Turbuhaler®. Despite its increasing usage, there are some concerns that patients on Turbuhaler® are not able to achieve adequate PIFR during acute exacerbation of asthma.
OBJECTIVE: This study aimed to assess the PIFR at resistance settings that matched Turbuhaler® in patients with acute exacerbation of asthma.
METHODOLOGY: A six-month cross-sectional study was conducted at the Emergency Department (ED) of Hospital Sultanah Bahiyah and Hospital Kulim, Kedah, Malaysia. Adult patients diagnosed with mild to moderate acute exacerbations of asthma were recruited. The PIFRs were measured using the In-Check DIAL G16 that was set to simulate the resistance of Turbuhaler® (R3). The PIFRs were assessed before (pre) and after (post) the initial bronchodilator (BD) treatment at the ED. The minimal required PIFR was defined as flow rates ≥ 30 L/min while a PIFR of 60 L/min was considered as optimal.
RESULTS: A total of 151 patients (81 females and 70 males) were recruited. The mean age was 37.5 years old with a range between 18 and 79 years old. The results showed that 98% (n = 148) of patients managed to achieve the minimal PIFR required for pre-BD. The mean PIFR pre-BD was 60 ± 18.5 L/min and post-BD was 70 ± 18.5 L/min. Furthermore, more than half (54%, n = 82) of the patients recorded PIFR ≥ 60 L/min during pre-BD, and about three-quarters (71%, n = 92) achieved PIFR ≥ 60 L/min post-BD. The PIFR showed a moderate correlation with peak expiratory flow rate (PEFR) (r = 0.55, 95% CI: 0.43-0.65, p

Matched MeSH terms: Dry Powder Inhalers