Influence of excipients on physical and aerosolization stability of spray dried high-dose powder formulations for inhalation
| Autor: | Qi Tony Zhou, Sonal V Bhujbal, Sharad Mangal, Hee Jun Park, Nivedita Shetty, Dmitry Zemlyanov |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Sucrose
Drug Compounding Pharmaceutical Science 02 engineering and technology Disaccharides 030226 pharmacology & pharmacy Article Excipients 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Stability Ciprofloxacin Leucine Administration Inhalation medicine Mannitol Lactose Desiccation Particle Size Ciprofloxacin Hydrochloride Aerosolization Aerosols Chromatography Chemistry Humidity 021001 nanoscience & nanotechnology Dry-powder inhaler Anti-Bacterial Agents Spray drying Powders 0210 nano-technology medicine.drug |
| Popis: | The aim of this study is to investigate the influence of excipients on physical and aerosolization stability of spray dried Ciprofloxacin dry powder inhaler formulations. The model drug, Ciprofloxacin hydrochloride, was co-spray dried with excipients such as disaccharides (sucrose, lactose, trehalose), mannitol and l -leucine. The spray dried samples were stored at two different relative humidity (RH) conditions of: (1) 20% and (2) 55% RH at 20 °C. Ciprofloxacin co-spray dried with disaccharides and l -leucine in the mass ratio of 1:1 demonstrated an increase in fine particle fraction (FPF) as compared with the spray dried Ciprofloxacin alone when stored at 20% RH. However, deterioration in FPF of Ciprofloxacin co-spray dried with disaccharide and mannitol was observed upon storage at 55% RH as compared to the corresponding formulations stored at 20% RH due to particle agglomeration. Whereas, 10% and 50% w/w l -leucine in the formulation showed no change in aerosol performance (FPF of 71.1 ± 3.5% and 79.5 ± 3.1%, respectively) when stored at 55% RH for 10 days as compared to 20% RH (FPF of 68.1 ± 0.3% and 73.6 ± 7.1%, respectively). l -Leucine demonstrated aerosolization stability by alleviating crystallization of Ciprofloxacin to some extent and preventing significant change in particle morphology. l -Leucine is well-recognized as aerosolization enhancer; our study has shown l -leucine is also a physical and aerosolization stabilizer for spray dried Ciprofloxacin DPI formulations. Such stability enhancing activities were attributed to the enrichment of l -leucine on the particle surface as confirmed by XPS data, and intermolecular interactions between l -leucine and Ciprofloxacin as measured by FT-IR. |
| Databáze: | OpenAIRE |
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