| Autor: |
Acosta, Maria F., Encinas-Basurto, David, Abrahamson, Michael D., Eedara, Basanth Babu, Hayes, Don, Fineman, Jeffrey R., Black, Stephen M., Mansour, Heidi M. |
| Zdroj: |
ACS Bio & Med Chem Au; December 2024, Vol. 4 Issue: 6 p300-318, 19p |
| Abstrakt: |
This study introduces novel cospray-dried (Co-SD) formulations of simvastatin, a Nrf2 activator ROCK inhibitor, with l-carnitine as molecular mixtures in various molar ratios for targeted pulmonary inhalation aerosol delivery in pulmonary hypertension, optimized for excipient-free dry powder inhalers (DPIs). The two components were spray-dried at various molar ratios by using different starting feed solution concentrations and process parameters. In addition to comprehensive physicochemical characterization, in vitro aerosol dispersion performance as DPIs using two FDA-approved DPI devices with different shear stress properties, in vitro viability as a function of dose on 2D human pulmonary cellular monolayers and on 3D small airway epithelia human primary cultures at the air–liquid interface (ALI), and in vitro transepithelial electrical resistance (TEER) at the ALI were conducted. Solid-state physicochemical characterization confirmed homogeneous molecular mixtures and the crystalline nature of the Co-SD formulations. In vitro aerosolization dispersion performance demonstrated that all Co-SD dual combination molecular mixtures aerosolized successfully with both human FDA-approved DPI devices, had ∼100% emitted dose, and good fine particle fraction values. The in vitro viability and TEER assays demonstrated that all formulations were safe to the human pulmonary cell as 2D and 3D cultures as a function of dose. |
| Databáze: |
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