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The interactive potential of polyethylene oxide as a tool to adjust drug delivery

MS, Pharmaceutical Affairs, Faculty of Health Sciences, University of the Witwatersrand / PEO (Polyethylene Oxide) is one of the most important biodegradable polymers used in pharmaceutical formulations, mainly because of its non-toxicity, high water-solubility and swellability, insensitivity to the pH of the biological medium and flexibility during dosage form production (Kim, 1995; Picker-Freyer, 2006; Kiss et al., 2008).
The lack of studies attempting to achieve controlled drug delivery of hydrophilic drugs has provided us with motivation to use a drug of this nature but we have combined it with a PEO-electrolyte combination in order to control drug delivery. This study was aimed at modifying the physicochemical and physicomechanical properties of PEO in order to influence the hydrodynamic diffusion of its three-dimensional network. Hence, through such alteration, it was envisaged that if drug is loaded into its PEO matrix, its solubility and dissolution can be regulated in order to achieve zero-order influx of dissolution medium. The interaction between PEO and electrolytes may allow for precipitation of ions on the polymer backbone. This would lead to the attraction of water molecules to the ions. As a result, this would cause dehydration of the polymer matrix, hence minimising its mobility and relaxation.
In this study, 36 PEO-electrolyte combinations were prepared by combining a high molecular weight PEO with different statistically planned combinations of electrolytes. The 36 formulations were microscopically analyzed and subjected to textural analysis. The salted-out PEO-electrolyte combinations were then further selected and analyzed. Assessment of the molecular structural transition and thermal compatibility analysis indicated minimal interaction between the electrolytes and PEO indicating that the polymer-electrolyte combination was stable enough to be employed as a medium for controlled drug release. The polymer-electrolyte combination was combined with a model drug, diphenhydramine HCl to form a tablet matrix and then subjected to dissolution. In vitro drug release varied depending on the different electrolytes and their combinations. The type of polymer, molecular weight of the polymer, concentration of the polymer, different electrolyte combinations and solubility of the drug played a significant role in controlling drug release.
After optimization of the fracture force, resilience and work performed values, results have established that equal concentrations of Na2CO3 and K2HPO4 are desirable for achieving controlled release of drug from the salted-out PEO combination in a zero-order manner. Furthermore, Na2CO3 and K2HPO4 had a significant influence on controlling the release of drug from the salted-out PEO combination due to crosslinking between PEO and the electrolytes ultimately leading to zero-order release kinetics. The salting-out of PEO notably modified the physicochemical and micromechanical properties of basic PEO, which demonstrably enhanced the ability of the sample to achieve controlled drug release. The formulation strategy employed in this study where in our sample drug, diphenhydramine HCl was combined with a PEO-electrolyte combination has shown promising results in regulating drug release.

Identiferoai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/9398
Date07 April 2011
CreatorsIsmail, Fatima
Source SetsSouth African National ETD Portal
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Formatapplication/pdf

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