PURPOSE: The objective of this study was to compare different techniques to enhance the solubility and dissolution rate, and hence the bioavailability of candesartan cilexetil. METHODS: To achieve this target, various techniques were employed such as solid dispersions, inclusion complexes, and preparation of candesartan nanoparticles. Following the preparations, all samples were characterized for their physicochemical properties, and the samples of the best results were subjected to further bioavailability studies. RESULTS: Results of dissolution studies revealed an increase in the dissolution rate of all samples. The highest dissolution rate was achieved using solid dispersion of the drug with PVP K-90 (1:4). Physicochemical investigations (XR, DSC, and FT-IR) suggested formation of hydrogen bonding and changing in the crystalline structure of the drug. Regarding the inclusion complexes, more stable complex was formed between HP-β-CD and CC compared to β-CD, as indicated by phase solubility diagrams. Antisolvent method resulted in the preparation of stable nanoparticles, as indicated by ζ potential, with average particle size of 238.9 ± 19.25 nm using PVP K-90 as a hydrophilic polymer. The best sample that gave the highest dissolution rate (CC/PVP K-90 1:4) was allowed for further pharmacokinetic studies using UPLC MS/MS assay of rabbit plasma. Results showed a significant increase in the bioavailability of CC from ~15% to ~48%. CONCLUSION: The bioavailability of CC was significantly improved from ~15% to ~48% when formulated as SDs with PVP K-90 with 1:4 drug:polymer ratio.
PURPOSE: The objective of this study was to compare different techniques to enhance the solubility and dissolution rate, and hence the bioavailability of candesartan cilexetil. METHODS: To achieve this target, various techniques were employed such as solid dispersions, inclusion complexes, and preparation of candesartan nanoparticles. Following the preparations, all samples were characterized for their physicochemical properties, and the samples of the best results were subjected to further bioavailability studies. RESULTS: Results of dissolution studies revealed an increase in the dissolution rate of all samples. The highest dissolution rate was achieved using solid dispersion of the drug with PVP K-90 (1:4). Physicochemical investigations (XR, DSC, and FT-IR) suggested formation of hydrogen bonding and changing in the crystalline structure of the drug. Regarding the inclusion complexes, more stable complex was formed between HP-β-CD and CC compared to β-CD, as indicated by phase solubility diagrams. Antisolvent method resulted in the preparation of stable nanoparticles, as indicated by ζ potential, with average particle size of 238.9 ± 19.25 nm using PVP K-90 as a hydrophilic polymer. The best sample that gave the highest dissolution rate (CC/PVP K-90 1:4) was allowed for further pharmacokinetic studies using UPLC MS/MS assay of rabbit plasma. Results showed a significant increase in the bioavailability of CC from ~15% to ~48%. CONCLUSION: The bioavailability of CC was significantly improved from ~15% to ~48% when formulated as SDs with PVP K-90 with 1:4 drug:polymer ratio.
Authors: Dimitrios Ntountaniotis; Ioannis Andreadelis; Tahsin F Kellici; Vlasios Karageorgos; Georgios Leonis; Eirini Christodoulou; Sofia Kiriakidi; Johanna Becker-Baldus; Evgenios K Stylos; Maria V Chatziathanasiadou; Christos M Chatzigiannis; Dimitrios E Damalas; Busecan Aksoydan; Uroš Javornik; Georgia Valsami; Clemens Glaubitz; Serdar Durdagi; Nikolaos S Thomaidis; Antonios Kolocouris; Janez Plavec; Andreas G Tzakos; George Liapakis; Thomas Mavromoustakos Journal: Mol Pharm Date: 2019-02-13 Impact factor: 4.939