Co-spraying of carriers (mannitol-lactose) as a method to improve aerosolization performance of salbutamol sulfate dry powder inhaler

Ferdynand, Mickey Socrates; Nokhodchi, Ali

doi:10.1007/s13346-020-00707-6

Cited by 23 publications

(8 citation statements)

References 30 publications

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“…Among all formulations, F-8 showed the highest FPF of 82.5 ± 1.4%, with an ED of 77.9 ± 0.5%. As per the current literature, the obtained ED and FPF are acceptable [62,63].…”

Section: In Vitro Aerosolizationsupporting

confidence: 71%

Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin Dry Powder

et al. 2022

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SARS-CoV-2, the causative agent of COVID-19, predominantly affects the respiratory tract. As a consequence, it seems intuitive to develop antiviral agents capable of targeting the virus right on its main anatomical site of replication. Ivermectin, a U.S. FDA-approved anti-parasitic drug, was originally shown to inhibit SARS-CoV-2 replication in vitro, albeit at relatively high concentrations, which is difficult to achieve in the lung. In this study, we tested the spray-drying conditions to develop an inhalable dry powder formulation that could ensure sufficient antiviral drug concentrations, which are difficult to achieve in the lungs based on the oral dosage used in clinical trials. Here, by using ivermectin as a proof-of-concept, we evaluated spray-drying conditions that could lead to the development of antivirals in an inhalable dry powder formulation, which could then be used to ensure sufficient drug concentrations in the lung. Thus, we used ivermectin in proof-of-principle experiments to evaluate our system, including physical characterization and in vitro aerosolization of prepared dry powder. The ivermectin dry powder was prepared with a mini spray-dryer (Buchi B-290), using a 23 factorial design and manipulating spray-drying conditions such as feed concentration (0.2% w/v and 0.8% w/v), inlet temperature (80 °C and 100 °C) and presence/absence of L-leucine (0% and 10%). The prepared dry powder was in the size range of 1–5 μm and amorphous in nature with wrinkle morphology. We observed a higher fine particle fraction (82.5 ± 1.4%) in high feed concentration (0.8% w/v), high inlet temperature (100 °C) and the presence of L-leucine (10% w/w). The stability study conducted for 28 days confirmed that the spray-dried powder was stable at 25 ± 2 °C/<15% RH and 25 ± 2 °C/ 53% RH. Interestingly, the ivermectin dry powder formulation inhibited SARS-CoV-2 replication in vitro with a potency similar to ivermectin solution (EC50 values of 15.8 µM and 14.1 µM, respectively), with a comparable cell toxicity profile in Calu-3 cells. In summary, we were able to manipulate the spray-drying conditions to develop an effective ivermectin inhalable dry powder. Ongoing studies based on this system will allow the development of novel formulations based on single or combinations of drugs that could be used to inhibit SARS-CoV-2 replication in the respiratory tract.

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“…Among all formulations, F-8 showed the highest FPF of 82.5 ± 1.4%, with an ED of 77.9 ± 0.5%. As per the current literature, the obtained ED and FPF are acceptable [62,63].…”

Section: In Vitro Aerosolizationsupporting

confidence: 71%

Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin Dry Powder

et al. 2022

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“…The high FPF of the formulations F2 and F3 (containing leucine and Mg-St); 40.9% and 41.9%, respectively are the evidence of the greater dispersion and aerosolization of puerarin as compared to drug only formulation devoid of the excipients [ 40 ]. The recovered dose ranged between 98% to 100% for all the formulation mixtures [ 41 ]. Hence, it is recognized that the only lactose mixture can produce a promising FPF and RD, whereas, with the addition of other excipients like leucine and Mg-St, the amount of RD dose and ED has improved which contributed to better performance of the formulations.…”

Section: Resultsmentioning

confidence: 99%

Puerarin dry powder inhaler formulations for pulmonary delivery: Development and characterization

et al. 2021

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This study aims at developing and characterizing the puerarin dry powder inhaler (DPI) formulations for pulmonary delivery. The inhalable particles size (<2 μm) was accomplished by micronization and its morphology was examined by scanning electron microscopy (SEM). The puerarin-excipient interaction in powder mixtures was analyzed by using Fourier transform infrared spectroscopy (FTIR), Raman confocal microscopy, X-Ray powder Diffraction (XRD), and differential scanning calorimetry (DSC) methods. Using a Twin stage impinger (TSI), the in-vitro aerosolization of the powder formulations was carried out at a flow rate of 60 L/min and the drug was quantified by employing a validated HPLC method. No significant interactions between the drug and the excipients were observed in the powder formulations. The fine particle fraction (FPF) of the drug alone was 4.2% which has increased five to six-fold for the formulations with aerosolization enhancers. Formulation containing lactose as large carriers produced 32.7% FPF, which further increased with the addition of dispersibility enhancers, leucine and magnesium stearate (40.8% and 41.2%, respectively). The Raman and FTIR techniques are very useful tool for understanding structural integrity and stability of the puerarin in the powder formulations. The puerarin was found to be compatible with the excipients used and the developed DPI formulation may be considered as an efficient formulation for pulmonary delivery for the management of various diseases at a very low dose.

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Section: Resultsmentioning

confidence: 99%

“…Prior to the drying step, the surface tension of the feedstock was reduced because of the surfactant properties of NaGc. This reduces the size of the droplets produced during atomization and forms smaller particles that favor pulmonary delivery [34]. During the drying phase, water present in the droplets evaporates, and the smaller the size of the droplets, the faster the saturation and crystallization of L-leucine.…”

Section: Particle Morphologymentioning

confidence: 99%

Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium Glycocholate

et al. 2022

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This study aimed to prepare mucus-penetrating inhalable microparticles for dry powder inhalers and to evaluate their applicability in an asthma-induced rat model. Microparticles were prepared from water solutions containing tiotropium bromide, L-leucine, and sodium glycocholate (NaGc) as permeation enhancers using the spray drying method. Four formulations (SDL1, SDL2, SDL3, and SDL4) were used, depending on the various NaGc concentrations. Tiotropium microparticles were characterized by standard methods. Additionally, an asthma-induced rat model was used to confirm the effects of the formulations on lung function. Tiotropium microparticles with NaGc resulted in formulations with a more corrugated morphology and smaller particle size distribution than those without NaGc. SDL 1 had a rough surface with irregular morphology, and SDL 2, 3, and 4 had a corrugated morphology. All SDL formulations had an aerodynamic size of <3 µm. The microparticles with a corrugated morphology aerosolized better than SDL1 microparticles. The apparent permeability coefficient (Papp) values of SDL3 and SDL4 were significantly higher than those for raw tiotropium. In an in vivo study using an asthma-induced rat model, the specific airway resistance (Sraw), airway wall thickness, and mean alveolus size recovered to those of the negative control group in the SDL4 formulation.

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Co-spraying of carriers (mannitol-lactose) as a method to improve aerosolization performance of salbutamol sulfate dry powder inhaler

Cited by 23 publications

References 30 publications

Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin Dry Powder

Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin Dry Powder

Puerarin dry powder inhaler formulations for pulmonary delivery: Development and characterization

Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium Glycocholate

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