Design of Inhalable Solid Dosage Forms of Budesonide and Theophylline for Pulmonary Combination Therapy
| Autor: | Korbinian Löbmann, Eric Ofosu Kissi, Donglei Leng, Kaushik Thanki, Camilla Foged, Thomas Rades, Mingshi Yang, Elias Fattal |
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| Rok vydání: | 2018 |
| Předmět: |
Budesonide
Combination therapy Nozzle Pharmaceutical Science 02 engineering and technology Aquatic Science 030226 pharmacology & pharmacy Dosage form Suspension (chemistry) 03 medical and health sciences 0302 clinical medicine Suspensions Theophylline Drug Discovery Administration Inhalation medicine Humans Particle Size Dissolution Lung Ecology Evolution Behavior and Systematics Dosage Forms Ecology Chemistry Dry Powder Inhalers General Medicine 021001 nanoscience & nanotechnology Bronchodilator Agents Drug Combinations Spray drying Drug Therapy Combination Powders 0210 nano-technology Agronomy and Crop Science medicine.drug Nuclear chemistry |
| Zdroj: | AAPS PharmSciTech. 20(3) |
| ISSN: | 1530-9932 |
| Popis: | Corticosteroid resistance poses a major challenge to effective treatment of chronic obstructive pulmonary diseases. However, corticosteroid resistance can be overcome by co-administration of theophylline. The aim of this study was to formulate the corticosteroid budesonide with theophylline into inhalable dry powders intended for pulmonary combination therapy. Four types of spray-dried powders were prepared: (i) budesonide and theophylline co-dissolved and processed using a 2-fluid nozzle spray drier, (ii) budesonide nanocrystals and dissolved theophylline co-dispersed and processed using a 2-fluid nozzle spray drier, (iii) dissolved budesonide and dissolved theophylline processed using a 3-fluid nozzle spray drier, and (iv) budesonide nanocrystals and dissolved theophylline processed using a 3-fluid nozzle spray drier. Spray drying from the solutions resulted in co-amorphous (i) and partially amorphous powders (iii), whereas spray drying of the nanosuspensions resulted in crystalline products (ii and iv). Even though budesonide was amorphous in (i) and (iii), it failed to exhibit any dissolution advantage over the unprocessed budesonide. In contrast, the dissolution of budesonide from its nanocrystalline formulations, i.e., (ii) and (iv), was significantly higher compared to a physical mixture or unprocessed budesonide. Furthermore, the spray-dried powders obtained from the 2-fluid nozzle spray drier, i.e., (i) and (ii), exhibited co-deposition of budesonide and theophylline at the same weight ratio in the aerodynamic assessment using the New Generation Impactor. In contrast, the depositions of budesonide and theophylline deviated from the starting weight ratio in the aerodynamic assessment of spray-dried powders obtained from the 3-fluid nozzle spray drier, i.e., (iii) and (iv). Based on these results, the powders spray-dried from the suspension by using the 2-fluid nozzle spray drier, i.e., (ii), offered the best formulation properties given the physically stable crystalline solid-state properties and the co-deposition profile. |
| Databáze: | OpenAIRE |
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