Thesis (doctoral)--Ume̊a Universitet, 1982. / Extra t.p. with thesis statement inserted. eContent provider-neutral record in process. Description based on print version record. Includes bibliographies.

Thesis (M.A.)--University of Leicester in association with (University of Hong Kong), 1995. / Includes bibliographical reference. Also available in print.

A problem in modern, agile aircraft is the possibility of the pilot losing consciousness during manoeuvres which can impose forces (G) many times that of gravitational acceleration. There is a possibility that the next generation of agile aircraft will exceed the level of anti-G protection presently available and the possibility of pharmacological intervention had been considered as an additional means of raising G-tolerance. Arginine vasopressin plays an active role in maintaining blood pressure, particularly in hypovolaemic situations, by its powerful vasoconstrictive action and control of heart output. As a potential G protection agent AVP has the appeal of not appearing to produce hypertension. The human centrifuge has normally been used to investigate problems of acceleration protection, but because of the hostile environment and space restraints, it has been difficult to carry out systematic biochemical investigations and lower body negative pressure has been used to simulate the cardio-vascular stress of G. The level of plasma catecholamines and arginine vasopressin has been measured during different exposure levels to lower body negative pressure and following b blockade with Propranolol combined with lower body negative pressure. No correlation could be established between peripheral circulating plasma levels of catecholamines and arginine vasopressin for any of the experimental conditions. However, dramatic oscillations in plasma noradrenaline levels were seen and a distinct pattern of arginine vasopressin secretion was observed at presyncope. The role of arginine vasopressin during syncope was investigated and small increases in plasma levels of this vasoactive hormone appeared to play a protective role in some subjects. In subsequent experiments, a bolus of arginine vasopressin was injected prior to exposure to lower body negative pressure, but this did not appear to have any effect on tolerance to lower body negative pressure and in some subjects it was positively detrimental.

Class of 2005 Abstract / Objectives: To standardize six tablets that share a statistically insignificant in vitro dissolution profile consisting of an experimental mixture of oxycodone HCl paired with dextromethorphan. We wanted to see if the release dynamics were not statistically different in an aqueous environment utilizing testing via USP Apparatus II (rotating paddles) in order to establish a drug release profile. Methods: Six experimental formulation tablets of oxycodone/DM were placed in separate dissolution vessels. The medium contained 900ml of water (standard media per USP) at 37°C (standard temperature per USP). Samples were taken at the 1, 2, 4, 6, 8, and 24 hour time periods and quantified using HPLC. The aim of this experiment was not meant to simulate an in vivo environment but simply to gain preliminary data for future research. Results: A one-sample t-test was used to calculate significant differences between the release profiles of oxycodone and dextromethorphan. We found that the release of all 6 tablets were not significantly statistically different for active ingredients, oxycodone and dextromethorphan. This data validated our hypothesis that the six experimental tablets would release the active ingredients over a 24-hour period at very similar and statistically insignificant rates. Implications: We now have a tablet formulation that can be replicated and used for further research including animal studies, and possibly human clinical trials, in order to develop a new pharmacotherapeutic approach for pain management.

Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Jiří Doubek Supervisor: Dr. Georgios Paraskevopoulos, Ph.D. Title of Thesis: Calcium phosphate bone cements: Synthesis, characterization and drug release properties Non-healing bone traumas are currently a complication, which may disable a patient from active life for a long period. Due to the fact that bone mass consists mostly of hydroxyapatite, a derivative of calcium phosphate - calcium phosphate cement (CPC) - is studied as an injectable bone substitute. The cement's characteristics (low setting temperature, injectability, bioactivity, and resorbability) are very promising. Furthermore, the possibility to incorporate a drug in the formulation that would support the healing process opens a way for new therapeutic options. Firstly, the aim of this research was to synthesize a high-quality α-tricalcium phosphate (α-TCP) and characterize its properties. Subsequently, the prepared α-TCP was used for the preparation of an injectable and washout resistant cement paste. Finally, the properties of developed pure or ibuprofen-loaded cement were examined by X-ray diffraction, Raman spectra, compressive strength, scanning electron microscopy, and dissolution studies. The obtained data revealed that...

A zero dimensional single zone model was developed to determine the crank resoled heat release rate at various injection timings (15°-60° BTDC) and the associated uncertainties from a pilot ignited natural gas engine. The uncertainty analysis examines the percentage contribution from various sources of error, including cylinder pressure measurements, intake manifold pressure measurements, and the impact of assumptions such as constant versus temperature dependent specific heat ratios. In particular, uncertainty percentage contributions and uncertainty magnification factors were used to quantify and compare the uncertainties in heat release rates using temperature dependent specific heat ratio correlations to constant specific heat ratio assumption. It is demonstrated that the error associated with the constant specific heat ratio assumption contributes to about 40 percent error (full scale value) in the net heat release estimates in comparison to using temperature dependent specific heat ratio correlations.

No description available.

Hydrogels have successfully proved themselves useful for drug delivery applications and several delivery routes have been developed over the years. The particular interest in this work was to design, synthesise and evaluate in situ forming drug eluting hydrogels, which have the potential to ameliorate the healing of cardiovascular diseases. With this aim the anti-inflammatory and immunosuppressant drugs rapamycin (Ra) and dexamethasone (Dex) were made water soluble by conjugation with polyethylene glycol (PEG). Ra was attached pendant from the terminal of PEGs while Dex was incorporated into dendritic structures grown from PEGs. These conjugates were further crosslinked into hydrogels by either conjugate or thiol-ene addition. The gel degradation was tuned to take between 5 and 27 days by using gel building block combinations that induced either 2 or 4 hydrolytically labile bonds per crosslink or by varying the number of crosslinking sites of the building blocks. The use of thiol-ene addition prolonged the degradation time nearly seven folded compared to conjugate addition as a more stable crosslink was formed. Two different formulations for gelling via conjugate addition were used (acrylate-thiol or vinyl sulphone-thiol) to deliver Ra, which was carried by either a 4- or 2-armed PEG. The elution kinetic for the respective gel formulation was of zero order during 15 and 19 days of gel degradation. In addition, Ra was PEGylated via esters, with a distance of either one or two carbons to a nearby thio-ether functionality. The difference in ester conjugation resulted in a slight but significant change in drug-PEG conjugate stability, which was mirrored by the increased time to reach the half amount of total drug elution; from 9.3 to 10.2 days and from 5.1 to 9.7 days for the two gel formulations, respectively. Dexamethasone was incorporated via an ester into dendrons of first and second generation pending from 2- and 4-armed PEGs at loadings of 2, 4 or 6 Dex molecules per carrier molecule. The resulting elution kinetic was of zero order during degradation periods of 5-27 days. Released Dex still possessed biological activity as determined by an in vitro cell assay. The novelties in this thesis are: (A) slow release of rapamycin obtained by covalent incorporation into hydrogels, (B) the use of unique PEG-based dendrimers to incorporate dexamethasone into a hydrogel and (C) zero order sustained release of dexamethasone at physiological pH. / Hydrogeler har framgångsrikt visat sig användbara för att leverera läkemedel och ett flertal metoder har utvecklats de senaste 20 åren. Fokuset i den här avhandlingen ligger på att designa, framställa och utvärdera läkemedelsutsöndrande hydrogeler som spontanhärdar in situ, vilka har potential att förbättra läkningen efter kardiovaskulär sjukdom. Med det syftet gjordes de anti-inflammatoriska och immunsänkande läkemedlen rapamycin (Ra) och dexametason (Dex) vattenlösliga genom att konjugeras med polyetylenglygol (PEG). Ra fästes kovalent längst ut på PEGar medans Dex inkluderades i dendritiska strukturer vilka byggdes från ändpunkten av PEGar. De här konjugaten tvärbands till hydrogeler via antingen konjugerad addition eller radikal polymerisation. Nedbrytningen av gelerna trimmades till att ta mellan 5 och 27 dagar genom att använda kombinationer av gelbyggstenar som bildar antingen 2 eller 4 hydrolyserbara estrar per tvärbindning eller genom att variera antalet tvärbindningspunkter hos byggstenarna. Användandet av radikal polymerisation i sig ledde till att nedbrytningen av geler tog nära sju gånger längre tid jämfört med geler gjorda via konjugerad addition eftersom stabilare tvärbindningar då formas. Två olika kombinationer för härdning via konjugerad addition (akryl-tiol eller vinylsulfon-tiol) användes för att leverera Ra som bars av antingen en 4- eller 2-armad PEG. Utsöndringskinetiken av Ra för de två kombinationerna var av nollte ordningen under de 15 och 19 dagar som gelerna degraderade. Dessutom, Ra PEGylerades via estrar med ett avstånd på antingen ett eller två kol till en närliggande tioeter. Skillnaden i avstånd ledde till en liten men signifikant skillnad i stabiliteten hos Ra-PEG konjugaten, vilket speglades i den förlängda tiden att nå halva mängden av den totala läkemedelsutsöndringen; från 9.3 till 10.2 dagar och från 5.1 till 9.7 dagar för de två respektive gelkombinationerna. Dex kopplades in via en esterbindning till dendroner av första och andra generationen byggda från PEGar med 2 eller 4 armar, vilket resulterade i att 2, 4 eller 6 Dex levererades per bärarmolekyl. Dex eluerade med nollte ordningens kinetik under degraderingsperioder på mellan 5 och 27 dagar. Vidbehålllen biologisk aktivitet av eluerad Dex bekräftades genom cellexperiment in vitro. Nyheterna i den här avhandlingen består av: (A) kontrollerad utsöndring av rapamycin uppnådd genom kovalent inbindning till hydrogeler, (B) användandet av unika PEGbaserade dendrimerer för kovalent inbindning av dexametason till hydrogeler och (C) nollte ordningens utsöndring av dexametason vid fysiologiskt pH. / <p>QC 20130204</p>

Thesis (M.E.)--University of Waikato, 2008. / Title from PDF cover (viewed September 18, 2008) Includes bibliographical references (p. 66-70)

The use of controlled release dosage forms has increased significantly in recent years as they result in increased patient compliance and higher therapeutic efficiency. This research focused on the development of a once daily dosage form that could be used for the treatment of hypertension. Both a separate sustained release dosage of metoprolol tartrate and a combination dosage form that included both an immediate release hydrochlorothiazide and a sustained release metoprolol component, were developed and evaluated. A matrix tablet, consisting of an ethylcellulose ranulation of metoprolol tartrate compressed into a hydrophilic hydroxypropyl methylcellulose polymer matrix, effectively sustained metoprolol release over a 22-hour experimental period. A multiparticulate combination dosage form that consisted of six coated mini matrix tablets of metoprolol and a powder blend of hydrochlorothiazide packed into a gelatin capsule, displayed zero order release kinetics for metoprolol release over 22 hours (r2=0.9946). The release of hydrochlorothiazide was found to be comparable to that of a commercially available product tested. Differential Scanning Calorimetry was used to identify possible incompatibilities between MPTA and excipients initially, and long term stability testing was used to assess to behaviour of the dosage form. Dissolution testing of the dosage forms was performed using USP Apparatus III, which was found to be more discriminating between the batches assessed. Dissolution curves were evaluated for similarity and difference using f1 and f2 fit factors. Samples were analyzed using a high performance liquid chromatographic method that was developed and validated for the simultaneous determination of the compounds of interest. Various factors influencing drug release from the developed dosage forms were assessed and recommendations for further optimization of the formulation are made. Factors evaluated included the quantity of granulating fluid, matrix polymer content, drug load and process variables, including drying time and compression force. The influence of various coating levels on drug release was assessed and none of the levels assessed were found to adequately retarded drug release over a 22-hour period. Combinations of tablets coated to different levels allowed for the successful development of a sustained release metoprolol component, which could be included into the combination dosage form.