Amino acids improve aerosolization and chemical stability of potential inhalable amorphous Spray-dried ceftazidime for Pseudomonas aeruginosa lung infection

Adhikari, Bishal Raj; Sinha, Shubhra; Gordon, Keith C.; Das, Shyamal C.

doi:10.1016/j.ijpharm.2022.121799

Cited by 8 publications

(7 citation statements)

References 64 publications

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“…A significant powder deposition in the cloth filter beyond the cyclone separator was observed. The laboratory-grade spray dryers as the one used in this study, are known to exhibit poor yield due to the inefficacy of the cyclone separator in collecting powder particles [3,12]. A slight increase in yield with the use of leucine was observed and is consistent with results reported in the literature.…”

Section: Preparation Of the Spray-dried Formulationssupporting

confidence: 89%

“…The use of excipients reflects a strategy to address different challenges in the development and optimization of inhalable powders. For example, amino acids have been used to improve aerosolization as well as chemical aerosolization of ceftazidime in the concentration of ~20% w/w [3]. Similarly, trehalose was used as a bulking agent in attempts to prepare inhalable dry powder of roflumilast, a potent anti-inflammatory agent [4].…”

Section: Introductionmentioning

confidence: 99%

“…Pharmaceutics 2022, 14, 2618 2 of 11 the concentration of ~20% w/w [3]. Similarly, trehalose was used as a bulking agent in attempts to prepare inhalable dry powder of roflumilast, a potent anti-inflammatory agent [4].…”

Section: Introductionmentioning

confidence: 99%

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Amorphicity and Aerosolization of Soluplus-Based Inhalable Spray Dried Powders

Adhikari

Das

2022

Pharmaceutics

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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.

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Section: Preparation Of the Spray-dried Formulationssupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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Amorphicity and Aerosolization of Soluplus-Based Inhalable Spray Dried Powders

Adhikari

Das

2022

Pharmaceutics

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“…In prior research, TRP successfully stabilized inhaled formulations of amorphous ceftazidime. 44 The acidic/ basic pK a values of LEU and TRP were 2.5/9.4 and 2.3/9.7, respectively, suggestive of neutral amino acids. These amino acids were employed as the third components for designing coamorphous THE−LEV formulations.…”

Section: ■ Results and Discussionmentioning

confidence: 93%

Improvement in Inhalation Properties of Theophylline and Levofloxacin by Co-Amorphization and Enhancement in Its Stability by Addition of Amino Acid as a Third Component

Ueda,

Hirakawa,

Miyano

et al. 2023

Mol. Pharmaceutics

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“…They are water-soluble carriers of relatively low molecular weights that have suitable structural characteristics (α-carboxylate, α-amino group, and side chains) for forming bonds with APIs. Numerous studies have demonstrated how amino acids can enhance the stability and safety of APIs [ 18 , 19 , 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmaceutical Systems as a Strategy to Enhance the Stability of Oxytetracycline Hydrochloride Polymorphs in Solution

2023

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In order to improve the stability of oxytetracycline hydrochloride, a polymorphic antibiotic set of novel binary systems were developed using β-cyclodextrin and amino acids with different acid-basic characteristics as ligands. The formation constants for each system containing β-cyclodextrin, L-aspartic acid, histidine and N-acetylcysteine were determined by Scott’s method and statistical studies. The structure of the binary systems with β-cyclodextrin and N-acetylcysteine was elucidated by NMR experiments. The effect β-cyclodextrin and N-acetylcysteine on the polymorph’s chemical stability in aqueous and phosphate buffered saline solutions at 25 °C was monitored by an optimized and validated high-performance liquid chromatography method. The combination of N-acetylcysteine with the three polymorphs and the β-cyclodextrin system obtained with the form III demonstrated a reduction in the degradation rate of oxytetracycline hydrochloride in the aqueous solution when compared to each free form, with an increase of 20 h in the half time. It evidences that the use of amino acids as ligands constitutes an interesting alternative for pharmaceutical areas. In conclusion, based on the results obtained, these pharmaceutical systems could be candidates for the development of a pharmaceutical formulation for the administration of the drug through reconstituted solutions using the binary system as a promising tool for improving the stability of oxytetracycline hydrochloride polymorphs in solution.

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Amino acids improve aerosolization and chemical stability of potential inhalable amorphous Spray-dried ceftazidime for Pseudomonas aeruginosa lung infection

Cited by 8 publications

References 64 publications

Amorphicity and Aerosolization of Soluplus-Based Inhalable Spray Dried Powders

Amorphicity and Aerosolization of Soluplus-Based Inhalable Spray Dried Powders

Improvement in Inhalation Properties of Theophylline and Levofloxacin by Co-Amorphization and Enhancement in Its Stability by Addition of Amino Acid as a Third Component

Pharmaceutical Systems as a Strategy to Enhance the Stability of Oxytetracycline Hydrochloride Polymorphs in Solution

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