Development of flexible and dispersible oral formulations containing praziquantel for potential schistosomiasis treatment of pre-school age children
| Autor: | Ramona Trastullo, Nadia Passerini, Beatrice Albertini, Luisa Stella Dolci |
|---|---|
| Přispěvatelé: | Trastullo, Ramona, Dolci, Luisa Stella, Passerini, Nadia, Albertini, Beatrice |
| Rok vydání: | 2015 |
| Předmět: |
Chemistry
Pharmaceutical Neglected tropical disease Administration Oral Pharmaceutical Science Models Biological Praziquantel Dosage form Excipients chemistry.chemical_compound Granulation Differential scanning calorimetry Solid-state characterization Drug Stability X-Ray Diffraction parasitic diseases Spectroscopy Fourier Transform Infrared Paediatric dosage form Humans Schistosomiasis Technology Pharmaceutical Particle Size Solubility Powder mixture Anthelmintics Chromatography Calorimetry Differential Scanning Dose-Response Relationship Drug Extemporaneous aqueous suspension Granule (cell biology) Buffer solution Wet granulation Isomalt chemistry Child Preschool Sweetening Agents Stability |
| Zdroj: | International Journal of Pharmaceutics. 495:536-550 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2015.09.019 |
| Popis: | Praziquantel (PZQ), an anthelmintic drug used in developing countries for the treatment of schistosome infections, was processed using the fluid bed wet granulation technology to prepare fast dispersible granules, as an appropriate and flexible dosage form for pre-school-aged children. Granulation experiments were performed incorporating PZQ either in the powder mixture, according to the traditional way, or in the liquid phase containing wetting agents. In the powder mixture several excipients were tested: Flowlac 100 as filler, Galeniq 721 (isomalt) and Neosorb P 100 T (D-sorbitol) as sweeteners and PVP K30 as binder; while in the liquid phase Lutrol F68, Cremophor RH 40 or Tween 80 as surfactants were investigated. Different formulations loaded with 10% w/w (batches 1-8) and 20% w/w of PZQ (batches 9-13) were produced The majority of granules displayed good flow properties and uniform drug content. X-ray powder diffraction showed that PZQ remained in its original crystalline state, while differential scanning calorimetry and Fourier transform-infrared analysis evidenced the formation of chemical interactions among the ingredients. The solubilisation test performed in non-sink condition to reproduce the actual condition in which a child of 4 years takes the medicine revealed that granules quickly formed a very fine suspension in water (dV90 = 39.9 μm). Although after the granulation process the solubility of raw PZQ was not increased, adding the aqueous suspension to 500 ml of buffer solution of pH 1.5, simulating the fasted state of a child, 50% of the drug was dissolved after 30 min. After granule manipulation with milk and fruit juices, no PZQ degradation was observed during time. Finally, the selected granule formulation provided evidence to be stable even at hot and very humid climate (30°C/75% RH), at least for the examined time. |
| Databáze: | OpenAIRE |
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