Preparation, evaluation, and pharmacokinetics in beagle dogs of a taste-masked flunixin meglumine orally disintegrating tablet prepared using hot-melt extrusion technology and D-optimal mixture design
| Autor: | Guoqing Yan, Qiuling Liang, Hangping Chen, Liqin Wu, Xin Feng, Linjie Zhang, Ruihan Deng, Jiakang He, Yangfeng Xu, Xuemei Wen |
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| Rok vydání: | 2021 |
| Předmět: |
Orally disintegrating tablet
Materials science Chromatography Hydroxypropyl cellulose Drug Compounding Hot Melt Extrusion Technology Pharmaceutical Science Administration Oral Clonixin Microcrystalline cellulose chemistry.chemical_compound Dogs chemistry Pharmacokinetics Solubility Taste Ultimate tensile strength Animals Extrusion Magnesium stearate Tablets |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 168 |
| ISSN: | 1879-0720 |
| Popis: | Flunixin meglumine (FM) is a nonsteroidal anti-inflammatory drug limited by irritation of the respiratory tract and mucosa in veterinary tissue. This study aimed to develop a taste-masked FM solid dispersion (SD) by hot-melt extrusion (HME) and formulate an orally disintegrating tablet (ODT) with selected excipients by direct compression. Eudragit® E PO was chosen as the matrix, and HME parameters were optimized: extrusion temperature, 135℃; screw speed, 100 rpm; and drug loading, 20%. Characterization techniques proved that FM was rendered amorphous in the HME extrudate. In vitro dissolution studies showed that FM SD released significantly slower than the corresponding physical mixture in artificial saliva. Excipients were selected based on compression formability, disintegration, and solubility. A D-optimal mixture design was used to optimize the composition: 25% FM SD, 18.75% microcrystalline cellulose, 52.5% mannitol, 3.75% low-substituted hydroxypropyl cellulose, and 1% magnesium stearate. Taste-masked FM ODT had a tensile strength of 0.7 ± 0.01 MPa and a disintegration time of 17.6 ± 0.1 s. E-tongue and E-nose analysis showed that FM ODT had a better taste-masked effect than commercial granules. Finally, a pharmacokinetic study proved that the main pharmacokinetic parameters of FM ODT were not significantly different from those of commercial granules, which indicated that these formulations had similar pharmacokinetic behaviours in beagles. |
| Databáze: | OpenAIRE |
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