Opin vísindi

Mucoadhesive drug delivery systems for the treatment of oral mucosal conditions

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.advisor Sveinbjörn Gizurarson, William Peter Holbrook and Þórdís Kristmundsdóttir
dc.contributor.author Patlolla, Venu Gopal Reddy
dc.date.accessioned 2021-06-02T11:15:56Z
dc.date.available 2021-06-02T11:15:56Z
dc.date.issued 2021-06
dc.identifier.isbn 978-9935-9445-7-3
dc.identifier.uri https://hdl.handle.net/20.500.11815/2610
dc.description.abstract The oral mucosa is a convenient location where drug delivery systems could be employed to treat both local conditions as well as systemic delivery. It offers 4-4000 times more permeability relative to skin which makes it an ideal platform for delivering higher molecular weight compounds both for local as well as systemic delivery. The oral mucosa can be affected by some conditions that are local e.g., ulcerative conditions like aphthous ulcers, immunologically mediated conditions, hyperkeratosis and infections (bacterial, candida and virus (cold sores)). Some of these conditions require long-term clinical follow up which eventually could lead to drug resistance. There is a growing need to develop new treatments that are effective in reducing the inflammation and effectively treating the infections. Previous clinical trials and in vitro microbial tests proved that doxycycline is a promising alternative in downgrading the inflammation pathway and could be potentially useful in treatment of many oral conditions. Monocaprin is a lipid that is effective against various bacteria, yeast and viruses. It effectively healed cold sores in combination with doxycycline and treatment outcome was promising compared to the existing treatments. But the drawback was the stability of the compounds; doxycycline undergoes oxidation and epimerization while monocaprin undergoes hydrolysis and is also susceptible for acyl-migration in solutions and both the compounds need to be stabilized in formulations especially sensitive to aqueos formulations. So, the main aim of this project was focused on enhancing the stability of active components doxycycline and monocaprin and also stabilizing them in combination in a hydrogel formulation. The study also involved development of suitable HPLC/UPLC method for accurate chemical quantification of the active component. Further the physicochemical evaluation of the formulations was analyzed to optimize the formulations for the oral mucosal delivery. The formulations were also analyzed for mucoadhesion capacity and texture profile analysis to enhance the drug retention at application site and also to enhance the patient compliance. The doxycycline was successfully stabilized in aqueous formulation for a tested period of up to 5 years. A hydrogel containing combination of doxycycline and monocaprin was developed and both the active components were stabilized for a period up to 1 year at 4°C. The microparticles were further developed to enhance the doxycycline stability even at 25°C and films loaded with microparticles effectively stabilized doxycycline even at room temperature. Various buccal films with different polymeric blends and plasticizers were evaluated for their suitability for doxycycline stability and their effect on films, mechanical properties, swelling index, pH, mucoadhesive potential and in vitro release with varying release time profile ranging from immediate-intermediate-sustained films were developed and evaluated. Suitable polymers and plasticizers for doxycycline stability are reported. Selection of polymers based on film properties that can be tailored are discussed in this work. Overall, doxycycline formulation that is stable for 5 years was developed. A stable hydrogel containing combination of doxycycline and monocaprin was developed. An accurate HPLC method for monocaprin quantification was developed. Doxycycline was further stabilized in microparticles loaded buccal films even at room temperature. Effect of microparticles and their incorporation on doxycycline stability as well as film properties were evaluated. Suitable polymers and plasticizers for doxycycline, for buccal film development were studied and reported. This project successfully stabilized doxycycline in formulations, also in combination with monocaprin, that could deliver it for MMP inhibition for oral mucosa, were developed that could be commercially available.
dc.language.iso en
dc.publisher University of Iceland, School of Health Sciences, Faculty of Pharmaceutical Sciences
dc.rights info:eu-repo/semantics/embargoedAccess
dc.subject Oral mucosal
dc.subject Hydrogel
dc.subject Stability
dc.subject Doxycycline
dc.subject Monocaprin
dc.subject Munnhol
dc.subject Slímhúð
dc.subject Lyfjafræði
dc.subject Lyfjagerð
dc.subject Lyfjaefnafræði
dc.subject Doktorsritgerðir
dc.title Mucoadhesive drug delivery systems for the treatment of oral mucosal conditions
dc.type info:eu-repo/semantics/doctoralThesis
dc.contributor.department Lyfjafræðideild (HÍ)
dc.contributor.department Faculty of Pharmaceutical Sciences (UI)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)

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