Mechanistic understanding of bioenabling formulation approaches to improve oral bioavailability using porcine in vivo and in silico models
| dc.check.embargoformat | Embargo not applicable (If you have not submitted an e-thesis or do not want to request an embargo) | en |
| dc.check.info | Not applicable | en |
| dc.check.opt-out | Not applicable | en |
| dc.check.reason | Not applicable | en |
| dc.check.type | No Embargo Required | |
| dc.contributor.advisor | Griffin, Brendan T. | en |
| dc.contributor.advisor | O'Driscoll, Caitriona M. | en |
| dc.contributor.author | O'Shea, Joseph P. | |
| dc.date.accessioned | 2018-09-05T11:13:17Z | |
| dc.date.available | 2018-09-05T11:13:17Z | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018 | |
| dc.description.abstract | Objectives: Mesoporous silicas (SLC) have demonstrated considerable potential to improve bioavailability of poorly soluble drugs by facilitating rapid dissolution and generating supersaturation. The addition of certain polymers can further enhance the dissolution of these formulations by preventing drug precipitation. This study uses fenofibrate as a model drug to investigate the performance of an SLC-based formulation, delivered with hydroxypropyl methylcellulose acetate succinate (HPMCAS) as a precipitation inhibitor, in pigs. The ability of biorelevant dissolution testing to predict the in vivo performance was also assessed. Key findings: Fenofibrate-loaded mesoporous silica (FF-SLC), together with HPMCAS, displayed significant improvements in biorelevant dissolution tests relative to a reference formulation consisting of a physical mixture of crystalline fenofibrate with HPMCAS. In vivo assessment in fasted pigs demonstrated bioavailabilities of 86.69 ± 35.37% with combination of FF-SLC and HPMCAS in capsule form and 75.47 ± 14.58% as a suspension, compared to 19.92 ± 9.89% with the reference formulation. A positive correlation was identified between bioavailability and dissolution efficiency. Conclusions: The substantial improvements in bioavailability of fenofibrate from the SLC-based formulations confirm the ability of this formulation strategy to overcome the dissolution and solubility limitations, further raising the prospects of a future commercially available SLC-based formulation. | en |
| dc.description.status | Not peer reviewed | en |
| dc.description.version | Accepted Version | |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | O'Shea, J. P. 2018. Mechanistic understanding of bioenabling formulation approaches to improve oral bioavailability using porcine in vivo and in silico models. PhD Thesis, University College Cork. | en |
| dc.identifier.endpage | 244 | en |
| dc.identifier.uri | https://hdl.handle.net/10468/6710 | |
| dc.language.iso | en | en |
| dc.publisher | University College Cork | en |
| dc.rights | © 2018, Joseph P. O'Shea. | en |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | en |
| dc.subject | Poorly water soluble drugs (PWSD) | en |
| dc.subject | Pig model | en |
| dc.subject | Biorelevant dissolution testing | en |
| dc.subject | In vitro in vivo correlations (IVIVC) | en |
| dc.subject | Physiologically based pharmacokinetic modelling | en |
| dc.subject | Lipid based formulations | en |
| dc.subject | Food effect | en |
| dc.subject | Mesoporous silica | en |
| dc.subject | Bioenabling formulations | en |
| dc.subject | Formulation screening | en |
| dc.subject | Oral drug absorption | en |
| dc.subject | Preclinical animal model | en |
| dc.thesis.opt-out | false | |
| dc.title | Mechanistic understanding of bioenabling formulation approaches to improve oral bioavailability using porcine in vivo and in silico models | en |
| dc.type | Doctoral thesis | en |
| dc.type.qualificationlevel | Doctoral | en |
| dc.type.qualificationname | PhD | en |
| ucc.workflow.supervisor | brendan.griffin@ucc.ie |
