Optimization of methionine in inhalable High-dose Spray-dried amorphous composite particles using response surface Method, infrared and low frequency Raman spectroscopy

Adhikari, Bishal Raj; Bērziņš, Kārlis; Fraser‐Miller, Sara J.; Cavallaro, Alex; Gordon, Keith C.; Das, Shyamal C.

doi:10.1016/j.ijpharm.2021.121446

Cited by 3 publications

(2 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, leucine improved the FPF of kanamycin from 48 to 73% when 5% leucine was used [22]. Such discrepancy in aerosolization enhancement behavior of amino acids is assumed to fragment from the multitude of factors such as particle size, density, surface asperity, surface enrichment, and relative intrinsic cohesive property of drugs/excipients used, which can dictate the aerosol performance of spray-dried particles [2,14,23,24]. to fragment from the multitude of factors such as particle size, density, surface asperity, surface enrichment, and relative intrinsic cohesive property of drugs/excipients used, which can dictate the aerosol performance of spray-dried particles [2,14,23,24].…”

Section: Aerosol Performance Of the Powdersmentioning

confidence: 99%

Amorphicity and Aerosolization of Soluplus-Based Inhalable Spray Dried Powders

Adhikari

Das

2022

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

Soluplus is a polymer that has been explored to prepare nanocomposites for pulmonary drug delivery and is non-toxic. However, its aerosolization attributes when spray-dried have not been investigated. Hence, this work aimed to investigate the aerosol performance of soluplus-based spray-dried powders. In addition, the potential use of leucine to improve the aerosolization of such particles was also investigated by including leucine at 10 or 20% w/w. 4% w/w salbutamol was used as a model drug in all the formulations primarily to aid quantification during aerosolization evaluation and for assessing the interaction between the drug and soluplus using infrared spectroscopy with the multivariate analysis approach of principal component analysis (PCA). Three formulations (4% salbutamol/96% soluplus, 4% salbutamol/86% soluplus/10% leucine, 4% salbutamol/76% soluplus/20% leucine) were prepared. The formulations were characterized in terms of solid-state, water content, particle size/morphology, and aerosolization. Similarly, two additional formulations (14% salbutamol/86% soluplus and 24% salbutamol/76% soluplus) were prepared to assess potential non-covalent interactions between salbutamol and soluplus. The formulations with only salbutamol and soluplus were amorphous, as evident from X-ray diffraction. Leucine was crystalline in the formulations. All the spray-dried formulations were irregular spheres with surface corrugation. The 96% soluplus powder showed an emitted fraction (EF) and fine particles fraction (FPF) of 91.9 and 49.8%, respectively. The inclusion of leucine at 10% did not increase the EF; however, an increase in FPF (69.7%) was achieved with 20% leucine. PCA of the infrared spectra suggested potential non-covalent interactions between salbutamol and soluplus. It hinted at the potential involvement of ketone groups of the excipient. This study concludes that soluplus-based spray-dried powder with or without leucine can potentially be utilized for pulmonary drug delivery. In addition, PCA can effectively be utilized in assessing interactions and overcoming limitations associated with visual assessment of the spectra of such formulations.

show abstract

Section: Aerosol Performance Of the Powdersmentioning

confidence: 99%

Amorphicity and Aerosolization of Soluplus-Based Inhalable Spray Dried Powders

Adhikari

Das

2022

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…All these factors make DPIs an ideal dosage form for SARS-CoV-2-infected patients, which can reduce the virus spreading as well. Spray-drying is a popular technique for producing such dry powder [ 34 , 35 ] because it is faster, more reproducible, and less expensive than other powder production processes [ 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Spray-Dried Inhalable Microparticles Combining Remdesivir and Ebselen against SARS-CoV-2 Infection

Saha,

Sinha,

Harfoot

et al. 2023

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

There is a continuous effort to develop efficient treatments for coronavirus disease 2019 (COVID-19) and other viral respiratory diseases. Among the different strategies, inhaled treatment is considered one of the most logical and efficient approaches to treating COVID-19, as the causative “SARS-CoV-2 virus RNA” predominantly infects the respiratory tract. COVID-19 treatments initially relied on repurposed drugs, with a few additional strategies developed during the last two years, and all of them are based on monotherapy. However, drug combinations have been found to be more effective than monotherapy in other viral diseases such as HIV, influenza, and hepatitis C virus. In the case of SARS-CoV-2 infection, in vitro studies have shown synergistic antiviral activity combining remdesivir with ebselen, an organoselenium compound. Therefore, these drug combinations could ensure better therapeutic outcomes than the individual agents. In this study, we developed a dry powder formulation containing remdesivir and ebselen using a spray-drying technique and used L-leucine as an aerosolization enhancer. The prepared dry powders were spherical and crystalline, with a mean particle size between 1 and 3 µm, indicating their suitability for inhalation. The emitted dose (ED) and fine particle fraction (FPF) of remdesivir- and ebselen-containing dry powders were ~80% and ~57% when prepared without L-leucine. The ED as well as the FPF significantly increased with values of >86% and >67%, respectively, when L-leucine was incorporated. More importantly, the single and combinational dry powder of remdesivir and ebselen showed minimal cytotoxicity (CC50 > 100 μM) in Calu-3 cells, retaining their anti-SARS-CoV-2 properties (EC50 2.77 to 18.64 μM). In summary, we developed an inhalable dry powder combination of remdesivir and ebselen using a spray-drying technique. The spray-dried inhalable microparticles retained their limited cytotoxicity and specific antiviral properties. Future in vivo studies are needed to verify the potential use of these remdesivir/ebselen combinational spray-dried inhalable microparticles to block the SARS-CoV-2 replication in the respiratory tract.

show abstract