Development and Permeability Testing of Self-Emulsifying Atorvastatin Calcium Pellets and Tablets of Compressed Pellets
| Autor: | Miltiadis Toskas, Yesim Karasulu, Ioannis Nikolakakis, Mine Diril |
|---|---|
| Přispěvatelé: | Ege Üniversitesi |
| Rok vydání: | 2019 |
| Předmět: |
Pellets
Bioengineering 02 engineering and technology lcsh:Chemical technology Friability 030226 pharmacology & pharmacy lcsh:Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pellet Chemical Engineering (miscellaneous) lcsh:TP1-1185 atorvastatin calcium Solubility drug release self-emulsifying pellets Chromatography Chemistry Process Chemistry and Technology self-emulsifying tablets 021001 nanoscience & nanotechnology Bioavailability Microcrystalline cellulose lcsh:QD1-999 Emulsion Drug delivery cytotoxicity permeability 0210 nano-technology |
| Zdroj: | Processes Volume 7 Issue 6 Processes, Vol 7, Iss 6, p 365 (2019) |
| ISSN: | 2227-9717 |
| Popis: | WOS: 000475306200049 Self-emulsifying pellets (SEPs) of Atorvastatin Calcium (AtrCa) were developed and processed into tablets (SETs). Self-emulsifying drug delivery system (SEDDS) composed of oleic acid, Tween 20, Span 80 and N-Methyl-2-pyrolidone gave great solubility improvement and was used as oil in water emulsion for the preparation of SEPs. Due to the high 60% w/w SEDDS content required to achieve a therapeutic dose in the final tablet form, sonication was necessary to improve fluidity and stability. Colloidal silicon dioxide (CSD) and microcrystalline cellulose (MCC) were the solids in the pellet formulation employed at a ratio 7:3, which enabled production of pellets with high SEDDS content and acceptable friability as well. Emulsions were characterized physico-chemically, SEPs for physical properties and reconstitution, and tablets of compressed pellets for mechanical strength, disintegration into pellets and drug release. SEPs compressed with 30% MCC at 60 MPa gave tablets of adequate strength that disintegrated rapidly into pellets within 1 min. Emulsion reconstitution took longer than drug release due to adsorption of SEDDS on CSD, implying dissolution at the pellet surface in parallel to that from the dispersed droplets. Compared to the commercial tablet, drug release from the self-emulsifying forms was faster at pH 1.2 where the drug solubility is poor, but slower at pH 6.8 where the solubility is higher. Permeability and cytotoxicity were also studied using Caco-2 cells. The results showed that drug transport from the apical to basolateral compartment of the test well was 1.27 times greater for SEPs than commercial tablets, but 0.86 times lower in the opposite direction. Statistical analysis confirmed the significance of these results. Toxicity was slightly reduced. Therefore, the increased permeability in conjunction with the protection of the drug being dissolved in the SEDDS droplets, may reduce the overall effect of presystemic metabolism and enhance bioavailability. Ege University Scientific Research Projects CoordinationEge University [14/ECZ/005] This work is part of the MSc research project of Mine Diril and was funded by Ege University Scientific Research Projects Coordination (Project No: 14/ECZ/005). |
| Databáze: | OpenAIRE |
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