Development of High Dose Oseltamivir Phosphate Dry Powder for Inhalation Therapy in Viral Pneumonia
Oseltamivir phosphate (OP) is an antiviral drug available only as oral therapy for the treatment of influenza and as a potential treatment option when in combination with other medication in the fight against the corona virus disease (COVID-19) pneumonia. In this study, OP was formulated as a dry po...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/12/1154 |
| _version_ | 1797546452705083392 |
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| author | Shahir Aziz Regina Scherlieβ Hartwig Steckel |
| author_facet | Shahir Aziz Regina Scherlieβ Hartwig Steckel |
| author_sort | Shahir Aziz |
| collection | DOAJ |
| description | Oseltamivir phosphate (OP) is an antiviral drug available only as oral therapy for the treatment of influenza and as a potential treatment option when in combination with other medication in the fight against the corona virus disease (COVID-19) pneumonia. In this study, OP was formulated as a dry powder for inhalation, which allows drug targeting to the site of action and potentially reduces the dose, aiming a more efficient therapy. Binary formulations were based on micronized excipient particles acting like diluents, which were blended with the drug OP. Different excipient types, excipient ratios, and excipient size distributions were prepared and examined. To investigate the feasibility of delivering high doses of OP in a single dose, 1:1, 1:3, and 3:1 drug/diluent blending ratios have been prepared. Subsequently, the aerosolization performance was evaluated for all prepared formulations by cascade impaction using a novel medium-resistance capsule-based inhaler (UNI-Haler). Formulations with micronized trehalose showed relatively excellent aerosolization performance with highest fine-particle doses in comparison to examined lactose, mannitol, and glucose under similar conditions. Focusing on the trehalose-based dry-powder inhalers’ (DPIs) formulations, a physicochemical characterization of extra micronized grade trehalose in relation to the achieved performance in dispersing OP was performed. Additionally, an early indication of inhaled OP safety on lung cells was noted by the viability MTT assay utilizing Calu-3 cells. |
| first_indexed | 2024-03-10T14:30:19Z |
| format | Article |
| id | doaj.art-40a5698dddfb40118bfc41a453662d9a |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T14:30:19Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-40a5698dddfb40118bfc41a453662d9a2023-11-20T22:38:22ZengMDPI AGPharmaceutics1999-49232020-11-011212115410.3390/pharmaceutics12121154Development of High Dose Oseltamivir Phosphate Dry Powder for Inhalation Therapy in Viral PneumoniaShahir Aziz0Regina Scherlieβ1Hartwig Steckel2Department of Pharmaceutical Technology, Faculty of Pharmacy, German University in Cairo, Cairo 11835, EgyptDepartment of Pharmaceutics and Biopharmaceutics, Kiel University, D-24118 Kiel, GermanyDeva Holding A.S., Istanbul 34303, TurkeyOseltamivir phosphate (OP) is an antiviral drug available only as oral therapy for the treatment of influenza and as a potential treatment option when in combination with other medication in the fight against the corona virus disease (COVID-19) pneumonia. In this study, OP was formulated as a dry powder for inhalation, which allows drug targeting to the site of action and potentially reduces the dose, aiming a more efficient therapy. Binary formulations were based on micronized excipient particles acting like diluents, which were blended with the drug OP. Different excipient types, excipient ratios, and excipient size distributions were prepared and examined. To investigate the feasibility of delivering high doses of OP in a single dose, 1:1, 1:3, and 3:1 drug/diluent blending ratios have been prepared. Subsequently, the aerosolization performance was evaluated for all prepared formulations by cascade impaction using a novel medium-resistance capsule-based inhaler (UNI-Haler). Formulations with micronized trehalose showed relatively excellent aerosolization performance with highest fine-particle doses in comparison to examined lactose, mannitol, and glucose under similar conditions. Focusing on the trehalose-based dry-powder inhalers’ (DPIs) formulations, a physicochemical characterization of extra micronized grade trehalose in relation to the achieved performance in dispersing OP was performed. Additionally, an early indication of inhaled OP safety on lung cells was noted by the viability MTT assay utilizing Calu-3 cells.https://www.mdpi.com/1999-4923/12/12/1154oseltamivir phosphatetrehalosealternative carrierjet milldry-powder inhalationfine diluent |
| spellingShingle | Shahir Aziz Regina Scherlieβ Hartwig Steckel Development of High Dose Oseltamivir Phosphate Dry Powder for Inhalation Therapy in Viral Pneumonia Pharmaceutics oseltamivir phosphate trehalose alternative carrier jet mill dry-powder inhalation fine diluent |
| title | Development of High Dose Oseltamivir Phosphate Dry Powder for Inhalation Therapy in Viral Pneumonia |
| title_full | Development of High Dose Oseltamivir Phosphate Dry Powder for Inhalation Therapy in Viral Pneumonia |
| title_fullStr | Development of High Dose Oseltamivir Phosphate Dry Powder for Inhalation Therapy in Viral Pneumonia |
| title_full_unstemmed | Development of High Dose Oseltamivir Phosphate Dry Powder for Inhalation Therapy in Viral Pneumonia |
| title_short | Development of High Dose Oseltamivir Phosphate Dry Powder for Inhalation Therapy in Viral Pneumonia |
| title_sort | development of high dose oseltamivir phosphate dry powder for inhalation therapy in viral pneumonia |
| topic | oseltamivir phosphate trehalose alternative carrier jet mill dry-powder inhalation fine diluent |
| url | https://www.mdpi.com/1999-4923/12/12/1154 |
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