Development of a Novel Implant for Drug Delivery
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Haywood, Alison
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Norris, Ross
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Abstract
Background and aim: In situ gelling formulations are liquids that undergo a phase transition to form semi-solid gel structures within the physiological environment. Sustained release of drug products can therefore be delivered via injectable in situ gelling formulations where the gel formed in vivo acts as a drug reservoir, releasing drug via diffusion and/or degradation of the gel. Due to limitations of previously described in situ gelling formulations, the current research project aimed to address these issues and develop a biocompatible injectable in situ gelling formulation/s containing a hydrophilic polymer within a non-aqueous solvent that would gel upon contact with aqueous physiological fluid. The ideal formulation was developed to exhibit long-term stability, be able to release both hydrophilic and hydrophobic drugs over a sustained period of time without a significant initial drug burst, and be inexpensive to manufacture. Experimental: Preformulation studies were performed and then optimised to develop suitable formulations containing hydroxypropyl methylcellulose (HPMC) carboxymethyl cellulose (CMCS), or methylcellulose (MC). These lead formulations were characterised to determine suitability for injectable in situ gelling activity by assessing viscosity, syringeability and gelling behaviour, and then tested for physical stability over a 6 month period. In vitro drug release characteristics were determined for a range of hydrophilic and hydrophobic compounds before the final ideal compound, namely CMCS2a, was chosen for drug incorporation studies. A model drug, risperidone, was incorporated into the final formulation and tested for physical and chemical stability over an 8-week period.
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Thesis (PhD Doctorate)
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Doctor of Philosophy (PhD)
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School of Pharmacy
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The author owns the copyright in this thesis, unless stated otherwise.
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Subject
Novel implant
Injectable in situ gelling formulations
Hydroxypropyl methylcellulose
Carboxymethyl cellulose
Methylcellulose