Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization
Oral tadalafil (TD) proved promising in treating pediatric pulmonary arterial hypertension (PAH). However, to ensure higher efficacy and reduce the systemic side effects, targeted delivery to the lungs through nebulization was proposed as an alternative approach. This poorly soluble drug was previou...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/12/2717 |
| _version_ | 1797455751099187200 |
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| author | Bassant Elbardisy Nabila Boraie Sally Galal |
| author_facet | Bassant Elbardisy Nabila Boraie Sally Galal |
| author_sort | Bassant Elbardisy |
| collection | DOAJ |
| description | Oral tadalafil (TD) proved promising in treating pediatric pulmonary arterial hypertension (PAH). However, to ensure higher efficacy and reduce the systemic side effects, targeted delivery to the lungs through nebulization was proposed as an alternative approach. This poorly soluble drug was previously dissolved in nanoemulsions (NEs). However, the formulations could not resist aqueous dilution, which precluded its dilution with saline for nebulization. Thus, the current study aimed to modify the previous systems into dilutable TD-NEs and assess their suitability for a pulmonary application. In this regard, screening of various excipients was conducted to optimize the former systems; different formulations were selected and characterized in terms of physicochemical properties, nebulization performance, stability following sterilization, and biocompatibility. Results showed that the optimal system comprised of Capmul-MCM-EP:Labrafac-lipophile (1:1) (<i>w</i>/<i>w</i>) as oil, Labrasol:Poloxamer-407 (2:1) (<i>w</i>/<i>w</i>) as surfactant mixture (S<sub>mix</sub>) and water. The optimum formulation P2<sub>TD</sub> resisted aqueous dilution, exhibited reasonable drug loading (2.45 mg/mL) and globule size (25.04 nm), acceptable pH and viscosity for pulmonary administration, and could be aerosolized using a jet nebulizer. Moreover, P2<sub>TD</sub> demonstrated stability following sterilization and a favorable safety profile confirmed by both in-vitro and in-vivo toxicity studies. These favorable findings make P2<sub>TD</sub> promising for the treatment of pediatric PAH. |
| first_indexed | 2024-03-09T15:58:49Z |
| format | Article |
| id | doaj.art-e5797056d5dd49a1bf14c39a8b3b9e1b |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T15:58:49Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e5797056d5dd49a1bf14c39a8b3b9e1b2023-11-24T17:20:48ZengMDPI AGPharmaceutics1999-49232022-12-011412271710.3390/pharmaceutics14122717Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via NebulizationBassant Elbardisy0Nabila Boraie1Sally Galal2Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, EgyptOral tadalafil (TD) proved promising in treating pediatric pulmonary arterial hypertension (PAH). However, to ensure higher efficacy and reduce the systemic side effects, targeted delivery to the lungs through nebulization was proposed as an alternative approach. This poorly soluble drug was previously dissolved in nanoemulsions (NEs). However, the formulations could not resist aqueous dilution, which precluded its dilution with saline for nebulization. Thus, the current study aimed to modify the previous systems into dilutable TD-NEs and assess their suitability for a pulmonary application. In this regard, screening of various excipients was conducted to optimize the former systems; different formulations were selected and characterized in terms of physicochemical properties, nebulization performance, stability following sterilization, and biocompatibility. Results showed that the optimal system comprised of Capmul-MCM-EP:Labrafac-lipophile (1:1) (<i>w</i>/<i>w</i>) as oil, Labrasol:Poloxamer-407 (2:1) (<i>w</i>/<i>w</i>) as surfactant mixture (S<sub>mix</sub>) and water. The optimum formulation P2<sub>TD</sub> resisted aqueous dilution, exhibited reasonable drug loading (2.45 mg/mL) and globule size (25.04 nm), acceptable pH and viscosity for pulmonary administration, and could be aerosolized using a jet nebulizer. Moreover, P2<sub>TD</sub> demonstrated stability following sterilization and a favorable safety profile confirmed by both in-vitro and in-vivo toxicity studies. These favorable findings make P2<sub>TD</sub> promising for the treatment of pediatric PAH.https://www.mdpi.com/1999-4923/14/12/2717Tadalafilpulmonary hypertensionnebulizationnanoemulsionphosphodiesterase 5 inhibitororo-tracheal |
| spellingShingle | Bassant Elbardisy Nabila Boraie Sally Galal Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization Pharmaceutics Tadalafil pulmonary hypertension nebulization nanoemulsion phosphodiesterase 5 inhibitor oro-tracheal |
| title | Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization |
| title_full | Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization |
| title_fullStr | Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization |
| title_full_unstemmed | Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization |
| title_short | Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization |
| title_sort | tadalafil nanoemulsion mists for treatment of pediatric pulmonary hypertension via nebulization |
| topic | Tadalafil pulmonary hypertension nebulization nanoemulsion phosphodiesterase 5 inhibitor oro-tracheal |
| url | https://www.mdpi.com/1999-4923/14/12/2717 |
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