Formulation and In Vitro and In Silico Characterization of “Nano-in-Micro” Dry Powder Inhalers Containing Meloxicam
Pulmonary delivery has high bioavailability, a large surface area for absorption, and limited drug degradation. Particle engineering is important to develop inhalable formulations to improve the therapeutic effect. In our work, the poorly water-soluble meloxicam (MX) was used as an active ingredient...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/2/211 |
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| author | Petra Party Csilla Bartos Árpád Farkas Piroska Szabó-Révész Rita Ambrus |
| author_facet | Petra Party Csilla Bartos Árpád Farkas Piroska Szabó-Révész Rita Ambrus |
| author_sort | Petra Party |
| collection | DOAJ |
| description | Pulmonary delivery has high bioavailability, a large surface area for absorption, and limited drug degradation. Particle engineering is important to develop inhalable formulations to improve the therapeutic effect. In our work, the poorly water-soluble meloxicam (MX) was used as an active ingredient, which could be useful for the treatment of non-small cell lung cancer, cystic fibrosis, and chronic obstructive pulmonary disease. We aimed to produce inhalable “nano-in-micro” dry powder inhalers (DPIs) containing MX and additives (poly-vinyl-alcohol, leucine). We targeted the respiratory zone with the microcomposites and reached a higher drug concentration with the nanonized active ingredient. We did the following investigations: particle size analysis, morphology, density, interparticular interactions, crystallinity, in vitro dissolution, in vitro permeability, in vitro aerodynamics (Andersen cascade impactor), and in silico aerodynamics (stochastic lung model). We worked out a preparation method by combining wet milling and spray-drying. We produced spherical, 3–4 µm sized particles built up by MX nanoparticles. The increased surface area and amorphization improved the dissolution and diffusion of the MX. The formulations showed appropriate aerodynamical properties: 1.5–2.4 µm MMAD and 72–76% fine particle fraction (FPF) values. The in silico measurements proved the deposition in the deeper airways. The samples were suitable for the treatment of local lung diseases. |
| first_indexed | 2024-03-09T05:50:14Z |
| format | Article |
| id | doaj.art-76f898d8516d4e6d83f86a3ff4138243 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T05:50:14Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-76f898d8516d4e6d83f86a3ff41382432023-12-03T12:17:50ZengMDPI AGPharmaceutics1999-49232021-02-0113221110.3390/pharmaceutics13020211Formulation and In Vitro and In Silico Characterization of “Nano-in-Micro” Dry Powder Inhalers Containing MeloxicamPetra Party0Csilla Bartos1Árpád Farkas2Piroska Szabó-Révész3Rita Ambrus4Interdisciplinary Excellence Centre, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös street 6, 6720 Szeged, HungaryInterdisciplinary Excellence Centre, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös street 6, 6720 Szeged, HungaryCentre for Energy Research, Hungarian Academy of Sciences, Konkoly-Thege Miklós Street 29-33, 1121 Budapest, HungaryInterdisciplinary Excellence Centre, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös street 6, 6720 Szeged, HungaryInterdisciplinary Excellence Centre, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös street 6, 6720 Szeged, HungaryPulmonary delivery has high bioavailability, a large surface area for absorption, and limited drug degradation. Particle engineering is important to develop inhalable formulations to improve the therapeutic effect. In our work, the poorly water-soluble meloxicam (MX) was used as an active ingredient, which could be useful for the treatment of non-small cell lung cancer, cystic fibrosis, and chronic obstructive pulmonary disease. We aimed to produce inhalable “nano-in-micro” dry powder inhalers (DPIs) containing MX and additives (poly-vinyl-alcohol, leucine). We targeted the respiratory zone with the microcomposites and reached a higher drug concentration with the nanonized active ingredient. We did the following investigations: particle size analysis, morphology, density, interparticular interactions, crystallinity, in vitro dissolution, in vitro permeability, in vitro aerodynamics (Andersen cascade impactor), and in silico aerodynamics (stochastic lung model). We worked out a preparation method by combining wet milling and spray-drying. We produced spherical, 3–4 µm sized particles built up by MX nanoparticles. The increased surface area and amorphization improved the dissolution and diffusion of the MX. The formulations showed appropriate aerodynamical properties: 1.5–2.4 µm MMAD and 72–76% fine particle fraction (FPF) values. The in silico measurements proved the deposition in the deeper airways. The samples were suitable for the treatment of local lung diseases.https://www.mdpi.com/1999-4923/13/2/211dry powder inhalernanomeloxicamwet millingspray-dryingAndersen cascade impactor |
| spellingShingle | Petra Party Csilla Bartos Árpád Farkas Piroska Szabó-Révész Rita Ambrus Formulation and In Vitro and In Silico Characterization of “Nano-in-Micro” Dry Powder Inhalers Containing Meloxicam Pharmaceutics dry powder inhaler nano meloxicam wet milling spray-drying Andersen cascade impactor |
| title | Formulation and In Vitro and In Silico Characterization of “Nano-in-Micro” Dry Powder Inhalers Containing Meloxicam |
| title_full | Formulation and In Vitro and In Silico Characterization of “Nano-in-Micro” Dry Powder Inhalers Containing Meloxicam |
| title_fullStr | Formulation and In Vitro and In Silico Characterization of “Nano-in-Micro” Dry Powder Inhalers Containing Meloxicam |
| title_full_unstemmed | Formulation and In Vitro and In Silico Characterization of “Nano-in-Micro” Dry Powder Inhalers Containing Meloxicam |
| title_short | Formulation and In Vitro and In Silico Characterization of “Nano-in-Micro” Dry Powder Inhalers Containing Meloxicam |
| title_sort | formulation and in vitro and in silico characterization of nano in micro dry powder inhalers containing meloxicam |
| topic | dry powder inhaler nano meloxicam wet milling spray-drying Andersen cascade impactor |
| url | https://www.mdpi.com/1999-4923/13/2/211 |
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