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Solid drug dispersions and mucoadhesive formulations with poly(2-oxazolines), poly(N-(2-hydroxylpopyl)methacrylamide) and their derivatives

Shan, X. (2021) Solid drug dispersions and mucoadhesive formulations with poly(2-oxazolines), poly(N-(2-hydroxylpopyl)methacrylamide) and their derivatives. PhD thesis, University of Reading

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To link to this item DOI: 10.48683/1926.00105201


The first chapter provides an overview on intermolecular interactions in solid dispersions of amide-containing nonionic water-soluble polymers including polyvinyl pyrrolidone (PVP), polyvinylpyrrolidone-co-vinyl acetate (PVP/VA), poly(N-vinyl caprolactam)–polyvinyl acetate–polyethylene glycol graft copolymer (Soluplus) and poly(2-oxazolines). Chapters 2 and 3 focus on the effects of structure and properties of PVP and poly(2-oxazolines) on solid dispersions. A series of poly(2-oxazolines) with equivalent degrees of polymerization were synthesized and these polymers and PVP were used to prepare solid dispersions with haloperidol or ibuprofen. Chapter 2 demonstrated that increasing the number of hydrophobic groups (-CH2- and -CH3) in the polymer resulted in greater inhibition of crystallinity of haloperidol. Interestingly, drug crystallization inhibition by poly(2- isopropyl-2-oxazoline) was lower than with its isomeric poly(2-propyl-2-oxazoline) because of the semi-crystalline nature of the former polymer. In order to explore the impacts of both polymer hydrophobicity and drug–polymer hydrogen bonding, in chapter 3, ibuprofen, a hydrophobic crystalline drug and strong hydrogen bond donor (because of its carboxylic group), was selected to prepare solid dispersions with poly(2-oxazolines) and PVP. Chapter 3 indicates the crystallinity disruption is predominantly due to hydrogen bonding between the drug molecule (ibuprofen) and the polymer. Both chapters show the crystallization inhibition was consistent with drug dissolution studies using these solid dispersions, with the exception of poly(2- propyl-2-oxazoline), which exhibited lower critical solution temperature that affected the release of haloperidol and ibuprofen. Chapter 4 and 5 investigate the mucoadhesion properties of modified poly(2-ethyl2-oxazoline) and poly(N-(2-hydroxylpropyl)methacrylamide) (PHPMA), respectively. In chapter 4, the presence of methacryloyl groups and residual amines in methacrylated poly(2-ethyl-2-oxazoline) had a strong synergistic effect on the mucoadhesive properties of these polymers. In chapter 5, the presence of maleimide groups was shown to positively affect the mucoadhesive properties of PHPMA. These poly(2-ethyl-2-oxazoline) derivatives and PHPMA derivatives have significant potential as mucoadhesive materials for formulation of dosage forms for nasal drug delivery. The final chapter discusses the general conclusions and possible future work. The poly(2-oxazolines) and functionalized derivatives appear to offer great potential in pharmaceutical applications

Item Type:Thesis (PhD)
Thesis Supervisor:Khutoryanskiy, V. and Williams, A.
Thesis/Report Department:School of Pharmacy
Identification Number/DOI:
Divisions:Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group
ID Code:105201


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