Drug dissolution from mesoporous silica systems

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dc.contributor.advisor Crean, Abina en
dc.contributor.author McCarthy, Carol A.
dc.date.accessioned 2019-09-19T10:06:15Z
dc.date.issued 2018
dc.date.submitted 2018
dc.identifier.citation McCarthy, C. A. 2018. Drug dissolution from mesoporous silica systems. PhD Thesis, University College Cork. en
dc.identifier.endpage 269 en
dc.identifier.uri http://hdl.handle.net/10468/8571
dc.description.abstract Mesoporous silica materials have been investigated as novel formulation aids for oral drug delivery due to their drug solubility enhancing characteristics. However, the mechanism of drug release from these systems is not well understood. Several studies have reported unexplained incomplete release from mesoporous silica carriers. It has been reported, in other research fields, that passive drug adsorption onto the silica surface is possible. However, the implications for this behaviour on drug release from silica systems has not been considered to date. Dissolution studies involving these formulations are generally conducted using Type II dissolution apparatus under sink conditions with traditional simple buffer media. In this thesis, the suitability of this dissolution approach for mesoporous silica systems is considered. The overall aim of this thesis was to investigate factors influencing drug adsorption and release from mesoporous silica systems to enhance understanding of their drug release profiles. This thesis began with a comprehensive overview of the literature which identified the gaps in knowledge in this area. Based on these findings, the hypothesis, aims and objectives were developed. The four research chapters were each dedicated to factors which could potentially affect drug release; formulation excipients, dissolution medium, drug/silica interactions and dissolution apparatus. The role of drug adsorption on the silica surface was explored across several of the chapters using adsorption isotherms, adsorption models and spectroscopic techniques. Several aspects of dissolution experimental design were investigated including sink and supersaturating conditions, traditional simple buffer media versus biorelevant media and Type II (paddle) apparatus versus Type IV (flow-through cell) and a Transfer model (incorporating an SGF to FaSSIF-V2 media transfer). Finally, the results of in vitro dissolution studies were compared to in vivo performance in a fasting pig model. The literature review demonstrated the gap in knowledge concerning the mechanism of drug release from mesoporous silica systems. This informed the central themes of the thesis which were explored in four research chapters. In Chapter 3, it was determined that formulation excipients which can reduce surface tension of the dissolution media (e.g. surfactants) can significantly increase drug release from mesoporous silica carriers. Passive drug adsorption and competitive adsorption involving drug and surfactant molecules on the silica surface was also observed. Chapter 4 built on work from the previous chapter and demonstrated that components of biorelevant media that reduced surface tension can also enhance drug release from silica systems. This chapter established that the influence of biorelevant media extends beyond its impact on drug supersaturation promotion and that its use should also be recommended under sink conditions. In Chapter 5, the focus was placed on investigating drug/silica interactions under supersaturating conditions. It was determined these interactions occur through a hydrogen bonding process and not via non-specific hydrophobic interactions. It was determined that the dynamic equilibrium which exists between adsorbed and free drug during passive adsorption and dissolution can be related to the drug’s activity in solution. Finally, in Chapter 6, it was observed that dissolution experimental design can influence in vitro drug release from mesoporous silica systems. It was established that the Type IV apparatus incorporating an SGF -> FaSSIF-V2 transfer is the best predictor of in vivo performance. The findings of this thesis have made a significant contribution to enhancing knowledge on drug release from mesoporous silica systems. It provides robust recommendations for the design of in vitro dissolution studies involving mesoporous silica formulations including choice of dissolution media, drug supersaturation level and dissolution apparatus. Interesting results concerning the influence of drug activity in solution on the equilibrium process observed during drug adsorption and dissolution from mesoporous silica materials were documented. These findings open up interesting new avenues for future research in the field of mesoporous silica carriers for oral drug delivery. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2018, Carol A. McCarthy. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject Dissolution en
dc.subject Adsorption en
dc.subject Solubility enhancement en
dc.subject Formulation development en
dc.subject Biorelevant media en
dc.subject Isotherm en
dc.title Drug dissolution from mesoporous silica systems en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD en
dc.internal.availability Full text available en
dc.description.version Accepted Version
dc.contributor.funder European Regional Development Fund en
dc.contributor.funder Science Foundation Ireland en
dc.description.status Not peer reviewed en
dc.internal.school Pharmacy en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.entireThesis Entire Thesis Restricted
dc.check.embargoformat Apply the embargo to both hard bound copy and e-thesis (If you have submitted an e-thesis and a hard bound thesis and want to embargo both) en
ucc.workflow.supervisor a.crean@ucc.ie
dc.internal.conferring Autumn 2019 en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2275/IE/Synthesis and Solid State Pharmaceutical Centre (SSPC)/ en

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