Enhanced pulmonary delivery of spray-dried theophylline: investigation of the trehalose and amino acid combinations as innovative fine carriers
•Development of novel trehalose-based carriers combined with amino acids.•Repurposing low-dose theophylline for asthma treatment via dry powder inhalation.•Trehalose – Leucine combination enhanced the fine carrier properties.•Trehalose – Leucine combination enhanced the aerodynamic performance of th...
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| Published in | European journal of pharmaceutical sciences Vol. 209; p. 107109 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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Elsevier B.V
01.06.2025
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| Abstract | •Development of novel trehalose-based carriers combined with amino acids.•Repurposing low-dose theophylline for asthma treatment via dry powder inhalation.•Trehalose – Leucine combination enhanced the fine carrier properties.•Trehalose – Leucine combination enhanced the aerodynamic performance of theophylline.•Enhancement of the drug’s solubility, permeability, and dissolution rate.
The emergence of novel carrier systems for dry powder inhalers is an attractive research subject. Additionally, the site-specific pulmonary delivery of theophylline (THN) remains challenging. Therefore, the present research aims to assess the potential enhancement of THN local delivery to the deep lung via powder inhalation for asthma treatment by developing appropriate fine carriers utilizing the well-established spray-drying technique.
The preliminary study aimed to develop novel trehalose-based carrier systems combined with amino acids leucine, glycine, and arginine. Aqueous feedstock solutions were spray-dried, and the obtained microparticulate carriers were assessed. Subsequently, therapeutic powders were produced by spray drying ethanol 10 % solutions of THN combined with candidate-developed carriers. Following each sample preparation, it was subjected to structural, thermal, morphological, rheological, aerodynamic, and particle size distribution characterization. Furthermore, THN solubility was determined. In vitro drug release and diffusion, in vitro and in silico simulated lung deposition, and aerodynamic particle count were analyzed by applying samples equivalent to 10 mg of THN.
To summarize the outcomes, carriers composed of trehalose with either leucine or a leucine-glycine combination demonstrated superior respirable properties and were considered candidates for further development. THN co-spray-dried samples showed less crystalline structure and particle size of 4–5 µm, leading to profound solubility enhancement (⁓20 fold) and rapid drug release compared to the pure THN (⁓100 % in 5 min). The in vitro and in silico aerodynamic measurements demonstrated that the THN-trehalose-leucine combination had a significantly enhanced fine particle fraction (43 %), leading to higher deep lung deposition (36 %), and the aerodynamic counter confirmed the development of fine particles (mean=3.61 µm). Moreover, the in vitro experiments on the A549 cells demonstrated that the optimized formulation has a low cytotoxicity profile.
In conclusion, the acquired characteristics suggest that inhalable co-spray-dried THN with the trehalose-leucine fine carrier may be a practical approach for local asthma therapy.
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| AbstractList | •Development of novel trehalose-based carriers combined with amino acids.•Repurposing low-dose theophylline for asthma treatment via dry powder inhalation.•Trehalose – Leucine combination enhanced the fine carrier properties.•Trehalose – Leucine combination enhanced the aerodynamic performance of theophylline.•Enhancement of the drug’s solubility, permeability, and dissolution rate.
The emergence of novel carrier systems for dry powder inhalers is an attractive research subject. Additionally, the site-specific pulmonary delivery of theophylline (THN) remains challenging. Therefore, the present research aims to assess the potential enhancement of THN local delivery to the deep lung via powder inhalation for asthma treatment by developing appropriate fine carriers utilizing the well-established spray-drying technique.
The preliminary study aimed to develop novel trehalose-based carrier systems combined with amino acids leucine, glycine, and arginine. Aqueous feedstock solutions were spray-dried, and the obtained microparticulate carriers were assessed. Subsequently, therapeutic powders were produced by spray drying ethanol 10 % solutions of THN combined with candidate-developed carriers. Following each sample preparation, it was subjected to structural, thermal, morphological, rheological, aerodynamic, and particle size distribution characterization. Furthermore, THN solubility was determined. In vitro drug release and diffusion, in vitro and in silico simulated lung deposition, and aerodynamic particle count were analyzed by applying samples equivalent to 10 mg of THN.
To summarize the outcomes, carriers composed of trehalose with either leucine or a leucine-glycine combination demonstrated superior respirable properties and were considered candidates for further development. THN co-spray-dried samples showed less crystalline structure and particle size of 4–5 µm, leading to profound solubility enhancement (⁓20 fold) and rapid drug release compared to the pure THN (⁓100 % in 5 min). The in vitro and in silico aerodynamic measurements demonstrated that the THN-trehalose-leucine combination had a significantly enhanced fine particle fraction (43 %), leading to higher deep lung deposition (36 %), and the aerodynamic counter confirmed the development of fine particles (mean=3.61 µm). Moreover, the in vitro experiments on the A549 cells demonstrated that the optimized formulation has a low cytotoxicity profile.
In conclusion, the acquired characteristics suggest that inhalable co-spray-dried THN with the trehalose-leucine fine carrier may be a practical approach for local asthma therapy.
[Display omitted] The emergence of novel carrier systems for dry powder inhalers is an attractive research subject. Additionally, the site-specific pulmonary delivery of theophylline (THN) remains challenging. Therefore, the present research aims to assess the potential enhancement of THN local delivery to the deep lung via powder inhalation for asthma treatment by developing appropriate fine carriers utilizing the well-established spray-drying technique. The preliminary study aimed to develop novel trehalose-based carrier systems combined with amino acids leucine, glycine, and arginine. Aqueous feedstock solutions were spray-dried, and the obtained microparticulate carriers were assessed. Subsequently, therapeutic powders were produced by spray drying ethanol 10 % solutions of THN combined with candidate-developed carriers. Following each sample preparation, it was subjected to structural, thermal, morphological, rheological, aerodynamic, and particle size distribution characterization. Furthermore, THN solubility was determined. In vitro drug release and diffusion, in vitro and in silico simulated lung deposition, and aerodynamic particle count were analyzed by applying samples equivalent to 10 mg of THN. To summarize the outcomes, carriers composed of trehalose with either leucine or a leucine-glycine combination demonstrated superior respirable properties and were considered candidates for further development. THN co-spray-dried samples showed less crystalline structure and particle size of 4-5 µm, leading to profound solubility enhancement (⁓20 fold) and rapid drug release compared to the pure THN (⁓100 % in 5 min). The in vitro and in silico aerodynamic measurements demonstrated that the THN-trehalose-leucine combination had a significantly enhanced fine particle fraction (43 %), leading to higher deep lung deposition (36 %), and the aerodynamic counter confirmed the development of fine particles (mean=3.61 µm). Moreover, the in vitro experiments on the A549 cells demonstrated that the optimized formulation has a low cytotoxicity profile. In conclusion, the acquired characteristics suggest that inhalable co-spray-dried THN with the trehalose-leucine fine carrier may be a practical approach for local asthma therapy.The emergence of novel carrier systems for dry powder inhalers is an attractive research subject. Additionally, the site-specific pulmonary delivery of theophylline (THN) remains challenging. Therefore, the present research aims to assess the potential enhancement of THN local delivery to the deep lung via powder inhalation for asthma treatment by developing appropriate fine carriers utilizing the well-established spray-drying technique. The preliminary study aimed to develop novel trehalose-based carrier systems combined with amino acids leucine, glycine, and arginine. Aqueous feedstock solutions were spray-dried, and the obtained microparticulate carriers were assessed. Subsequently, therapeutic powders were produced by spray drying ethanol 10 % solutions of THN combined with candidate-developed carriers. Following each sample preparation, it was subjected to structural, thermal, morphological, rheological, aerodynamic, and particle size distribution characterization. Furthermore, THN solubility was determined. In vitro drug release and diffusion, in vitro and in silico simulated lung deposition, and aerodynamic particle count were analyzed by applying samples equivalent to 10 mg of THN. To summarize the outcomes, carriers composed of trehalose with either leucine or a leucine-glycine combination demonstrated superior respirable properties and were considered candidates for further development. THN co-spray-dried samples showed less crystalline structure and particle size of 4-5 µm, leading to profound solubility enhancement (⁓20 fold) and rapid drug release compared to the pure THN (⁓100 % in 5 min). The in vitro and in silico aerodynamic measurements demonstrated that the THN-trehalose-leucine combination had a significantly enhanced fine particle fraction (43 %), leading to higher deep lung deposition (36 %), and the aerodynamic counter confirmed the development of fine particles (mean=3.61 µm). Moreover, the in vitro experiments on the A549 cells demonstrated that the optimized formulation has a low cytotoxicity profile. In conclusion, the acquired characteristics suggest that inhalable co-spray-dried THN with the trehalose-leucine fine carrier may be a practical approach for local asthma therapy. The emergence of novel carrier systems for dry powder inhalers is an attractive research subject. Additionally, the site-specific pulmonary delivery of theophylline (THN) remains challenging. Therefore, the present research aims to assess the potential enhancement of THN local delivery to the deep lung via powder inhalation for asthma treatment by developing appropriate fine carriers utilizing the well-established spray-drying technique. The preliminary study aimed to develop novel trehalose-based carrier systems combined with amino acids leucine, glycine, and arginine. Aqueous feedstock solutions were spray-dried, and the obtained microparticulate carriers were assessed. Subsequently, therapeutic powders were produced by spray drying ethanol 10 % solutions of THN combined with candidate-developed carriers. Following each sample preparation, it was subjected to structural, thermal, morphological, rheological, aerodynamic, and particle size distribution characterization. Furthermore, THN solubility was determined. In vitro drug release and diffusion, in vitro and in silico simulated lung deposition, and aerodynamic particle count were analyzed by applying samples equivalent to 10 mg of THN. To summarize the outcomes, carriers composed of trehalose with either leucine or a leucine-glycine combination demonstrated superior respirable properties and were considered candidates for further development. THN co-spray-dried samples showed less crystalline structure and particle size of 4-5 µm, leading to profound solubility enhancement (⁓20 fold) and rapid drug release compared to the pure THN (⁓100 % in 5 min). The in vitro and in silico aerodynamic measurements demonstrated that the THN-trehalose-leucine combination had a significantly enhanced fine particle fraction (43 %), leading to higher deep lung deposition (36 %), and the aerodynamic counter confirmed the development of fine particles (mean=3.61 µm). Moreover, the in vitro experiments on the A549 cells demonstrated that the optimized formulation has a low cytotoxicity profile. In conclusion, the acquired characteristics suggest that inhalable co-spray-dried THN with the trehalose-leucine fine carrier may be a practical approach for local asthma therapy. |
| ArticleNumber | 107109 |
| Author | Party, Petra Burián, Katalin Ambrus, Rita Paróczai, Dóra Nagy, Attila Soliman, Lomass Farkas, Árpád |
| Author_xml | – sequence: 1 givenname: Lomass surname: Soliman fullname: Soliman, Lomass organization: Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Szeged, Eötvös utca 6, 6720 Hungary – sequence: 2 givenname: Petra surname: Party fullname: Party, Petra organization: Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Szeged, Eötvös utca 6, 6720 Hungary – sequence: 3 givenname: Attila surname: Nagy fullname: Nagy, Attila organization: Department of Applied and Nonlinear Optics, HUN-REN Wigner Research Centre for Physics, Konkoly-Thege Miklós St. 29-33, 1121 Budapest, Hungary – sequence: 4 givenname: Árpád surname: Farkas fullname: Farkas, Árpád organization: Environmental Physics Department, HUN-REN Centre for Energy Research, Konkoly-Thege Miklós Street 29-33, Budapest 1121, Hungary – sequence: 5 givenname: Dóra surname: Paróczai fullname: Paróczai, Dóra organization: Department of Medical Microbiology and Immunobiology, University of Szeged, Dóm Square 10, H-6720 Sze-ged, Hungary – sequence: 6 givenname: Katalin surname: Burián fullname: Burián, Katalin organization: Department of Medical Microbiology and Immunobiology, University of Szeged, Dóm Square 10, H-6720 Sze-ged, Hungary – sequence: 7 givenname: Rita surname: Ambrus fullname: Ambrus, Rita email: ambrus.rita@szte.hu organization: Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Szeged, Eötvös utca 6, 6720 Hungary |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/40280283$$D View this record in MEDLINE/PubMed |
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| Keywords | Dry powder inhaler Spray drying In silico Trehalose Theophylline Andersen cascade impactor |
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| Snippet | •Development of novel trehalose-based carriers combined with amino acids.•Repurposing low-dose theophylline for asthma treatment via dry powder... The emergence of novel carrier systems for dry powder inhalers is an attractive research subject. Additionally, the site-specific pulmonary delivery of... |
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| SubjectTerms | Administration, Inhalation Amino Acids - administration & dosage Amino Acids - chemistry Andersen cascade impactor Bronchodilator Agents - administration & dosage Bronchodilator Agents - chemistry Drug Carriers - administration & dosage Drug Carriers - chemistry Drug Liberation Dry powder inhaler Dry Powder Inhalers Humans In silico Leucine - chemistry Lung - metabolism Particle Size Powders Solubility Spray Drying Theophylline Theophylline - administration & dosage Theophylline - chemistry Trehalose Trehalose - administration & dosage Trehalose - chemistry |
| Title | Enhanced pulmonary delivery of spray-dried theophylline: investigation of the trehalose and amino acid combinations as innovative fine carriers |
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