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dc.contributor.authorIsmail, Ali Abdien_NZ
dc.date.accessioned2007-03-26T10:03:18Z
dc.date.available2007-03-30T12:41:03Z
dc.date.issued2007en_NZ
dc.identifier.citationIsmail, A. A. (2007). Preformulation and Formulation of Steroids and Assessment of an Electronically Modulated Intravaginal Device for Induced Calving or Oestrous synchronization of Cattle. (Thesis, Doctor of Philosophy (PhD)). The University of Waikato, Hamilton, New Zealand. Retrieved from https://hdl.handle.net/10289/2654en
dc.identifier.urihttps://hdl.handle.net/10289/2654
dc.description.abstractDrug delivery technology is currently advancing faster than at any time in biotechnology history. The challenge of drug delivery is to achieve a controlled release of therapeutic agents over an extended period. Controlled release potentially offers significant advantages over conventional dosage forms, by eliminating both under- and overdosing while maintaining a desired range of drug concentrations. An existing drug regimen for induced calving produces a declining blood profile that does not mimic the naturally occurring, gradually increasing, cortisol blood level around parturition effectively, causing animal health issues. Likewise, while the existing progesterone controlled release systems for oestrous control successfully synchronise oestrus, it is however, associated with reduced fertility and as such other drugs have to be administered to improve the fertility during oestrus. Therefore, there is a need for a drug delivery system that is capable of delivering multiple drugs at various times and patterns. This research aimed to investigate, characterize, identify steroids with high absorption rates through vaginal mucosa and evaluate the potential of an electronic drug delivery system for the delivery of steroids for either the control of the bovine oestrous cycle or induced calving. In order to identify steroids with high absorption rates across the vaginal mucosa, an in vitro permeation method was developed to screen selected steroids for their ability to permeate artificial and biological membranes. The steroids were pre-formulated to enhance their solubility and permeation through these membranes. Analytical UV and HPLC assays to characterise the pure and formulated steroidal compounds were also developed and validated. An assessment of an intravaginal Electronically Modulated Intravaginal Device (EMID) for the control of the bovine oestrous cycle or induced calving was carried out. Five different release assessment methods were investigated and critically evaluated in order to identify the most appropriate release assessment method for the EMID. These were: 1) the Drug Dissolution Test, 2) a weight loss method, 3) the dispensed weight method, 4) the determination of piston travel distance method, and 5) the rod expulsion from the EMID method. The methods investigated were critically evaluated in terms of ease of use and automation, reproducibility and cost/time savings. Optimisation of various components and construction materials of the EMID were also investigated. Animal trials were carried out using the original EMID (manufactured from polypropylene polymer) and modified inserts (manufactured from high density polyethylene polymer) to determine their retention rate in the animals. Accelerated stability testing of progesterone in suspension, oestradiol-17 tablets, cloprostenol as a powder blend and the driving mechanism of the EMID were examined. The flux of the steroids was evaluated through poly-&-caprolactone and excised cow mucosa membranes using side-by-side permeation cells. Results indicated that progesterone followed by dexamethasone acetate and dexamethasone valerate showed higher permeability values through vaginal mucosa compared to dexamethasone or its other analogues. The weight loss method of the EMID proved to be an easy and appropriate method to measure the release rate from the EMID. A high density polyethylene polymer was identified as the most ideal body material for the insert compared to polypropylene body. Also double O-ring silicone, Elastollan WYO 1388-5 and solid silicone pistons were found to be amongst the best pistons tested and all performed well compared to other piston materials. There was a low retention rate with either the original EMID or the modified inserts. Further modification of retention wings of the EMID did not improve the retention rate, but a good blood profile response was obtained from cows treated with the complete EMID containing formulated progesterone. The formulations and driving mechanism were found to be stable under the tested conditions. Therefore, the EMID has potential for commercial application of induced calving or oestrous control per vaginum administration, reliant on improvement of its retention mechanism.en_NZ
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherThe University of Waikatoen_NZ
dc.rightsAll items in Research Commons are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectsteroidsen_NZ
dc.subjectdexamethasoneen_NZ
dc.subjectsteroids permeation across biological and non-biological membranesen_NZ
dc.subjectformulationen_NZ
dc.subjectHPLC analytical methodsen_NZ
dc.subjectelectronically modulated intravaginal deviceen_NZ
dc.subjectinduced calving and oestrous synchronisation..en_NZ
dc.titlePreformulation and Formulation of Steroids and Assessment of an Electronically Modulated Intravaginal Device for Induced Calving or Oestrous synchronization of Cattle.en_NZ
dc.typeThesisen_NZ
thesis.degree.disciplineScience and Engineeringen_NZ
thesis.degree.grantorUniversity of Waikatoen_NZ
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (PhD)en_NZ
uow.date.accession2007-03-26T10:03:18Zen_NZ
uow.date.available2007-03-30T12:41:03Zen_NZ
uow.identifier.adthttp://adt.waikato.ac.nz/public/adt-uow20070326.100318en_NZ
uow.date.migrated2009-06-12T04:51:34Zen_NZ
pubs.place-of-publicationHamilton, New Zealanden_NZ


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