Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium Glycocholate
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...
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MDPI AG
2022-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/7/1409 |
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| author | Yong-Bin Kwon Ji-Hyun Kang Young-Jin Kim Dong-Wook Kim Sung-Hoon Lee Chun-Woong Park |
| author_facet | Yong-Bin Kwon Ji-Hyun Kang Young-Jin Kim Dong-Wook Kim Sung-Hoon Lee Chun-Woong Park |
| author_sort | Yong-Bin Kwon |
| collection | DOAJ |
| description | 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 (P<sub>app</sub>) 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 (S<sub>raw</sub>), airway wall thickness, and mean alveolus size recovered to those of the negative control group in the SDL4 formulation. |
| first_indexed | 2024-03-09T06:04:36Z |
| format | Article |
| id | doaj.art-aa413624af824dd6935e7308a0361b79 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T06:04:36Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-aa413624af824dd6935e7308a0361b792023-12-03T12:06:11ZengMDPI AGPharmaceutics1999-49232022-07-01147140910.3390/pharmaceutics14071409Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium GlycocholateYong-Bin Kwon0Ji-Hyun Kang1Young-Jin Kim2Dong-Wook Kim3Sung-Hoon Lee4Chun-Woong Park5College of Pharmacy, Chungbuk National University, 194-21, Osongsangmyeong 1-ro, Heungdeok-gu, Cheongju 28160, KoreaCollege of Pharmacy, Chungbuk National University, 194-21, Osongsangmyeong 1-ro, Heungdeok-gu, Cheongju 28160, KoreaCollege of Pharmacy, Chungbuk National University, 194-21, Osongsangmyeong 1-ro, Heungdeok-gu, Cheongju 28160, KoreaCollege of Pharmacy, Wonkwang University, Iksan 54538, KoreaDepartment of Pharmaceutical Engineering, Cheongju University, Cheongju 28503, KoreaCollege of Pharmacy, Chungbuk National University, 194-21, Osongsangmyeong 1-ro, Heungdeok-gu, Cheongju 28160, KoreaThis 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 (P<sub>app</sub>) 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 (S<sub>raw</sub>), airway wall thickness, and mean alveolus size recovered to those of the negative control group in the SDL4 formulation.https://www.mdpi.com/1999-4923/14/7/1409tiotropiumsodium glycocholatepermeation enhanceraerodynamic propertiesCalu-3 cellasthma-induced rat model |
| spellingShingle | Yong-Bin Kwon Ji-Hyun Kang Young-Jin Kim Dong-Wook Kim Sung-Hoon Lee Chun-Woong Park Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium Glycocholate Pharmaceutics tiotropium sodium glycocholate permeation enhancer aerodynamic properties Calu-3 cell asthma-induced rat model |
| title | Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium Glycocholate |
| title_full | Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium Glycocholate |
| title_fullStr | Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium Glycocholate |
| title_full_unstemmed | Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium Glycocholate |
| title_short | Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium Glycocholate |
| title_sort | preparation and evaluation of mucus penetrating inhalable microparticles of tiotropium bromide containing sodium glycocholate |
| topic | tiotropium sodium glycocholate permeation enhancer aerodynamic properties Calu-3 cell asthma-induced rat model |
| url | https://www.mdpi.com/1999-4923/14/7/1409 |
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