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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

The influence of the application of pharmacokinetics on the effects of theophylline utilisation upon members of the Indian population.

Pillai, Goonaseelan. January 1989 (has links)
Theophylline is a dimethylated xanthine similar in structure to caffeine which is commonly found in tea, coffee and cola beverages (Hendeles and Weinberger, 1983; Rall, 1985). Clinically, its most important pharmacological action is the ability to relax bronchial smooth muscle throughout the bronchial tree (Persson, 1986). This effect has found extensive use in the treatment of asthma with the drug being recommended as the first line agent for chronic asthma (la/rate et ai, 1986). The observation that both beneficial effects as well as toxicity correlate with serum concentrations and that the drug displays a narrow therapeutic window (Finn et al, 1981; Hendeles and Matthay, 1986) has resulted in the recommendation that theophylline dosing be guided by serum concentration measurements (Hendeles and Weinberger, 1980; Whiting et al, 1984; Fitzpatrick and Moss-Barclay, 1985; Barlow et. al, 1988). However, this recommendation appears to have been largely ignored locally. In 1986, one of the first local Therapeutic Drug Monitoring Clinics for theophylline was established at R K Khan Provincial Hospital in Chatsworth, Durban. Preliminary results from this clinic confirmed the widespread use of standard theophylline dosing regimens and revealed that 68% (n = 44) of patients given these regimens had serum theophylline concentrations below the generally accepted therapeutic range (Pillai and Miller, 1988). Previous studies have assessed the influence of Therapeutic Drug Monitoring programmes in terms of the attainment of 'therapeutic' serum concentrations (Whiting et aI, 1984; Fitzpatrick and Moss-Barclay, 1985). This approach has been criticised and it has been recommended that clinical assessment should be the criterion. The purpose of this study was to investigate the influence of serum concentration monitoring on theophylline utilisation at the R K Khan Hospital in terms of clinical control of asthma symptoms. A secondary purpose of this study was to determine population pharmacokinetic parameters in Indian patients. In order to interpret the serum concentrations and make recommendations on dosage design for individual patients, the Bayesian technique of drug dose optimisation is used (Sheiner et aI, 1972). This technique has been shown to be accurate, precise and easy to use (Sheiner and Beal, 1982; Hurley and McNeil, 1988) particularly with currently available computer software. It has been emphasised, however, that for satisfactory performance of this technique, good initial estimates of the population parameter distributions are important (Whiting et al, 1986). Since this information is not available for the Indian population this study was undertaken. A knowledge of population pharmacokinetics can help one to choose initial dosage, to modify dosage appropriately in response to observed drug levels, to make rational decisions regarding drug regulatory requirements and toinvestigate and elucidate certain research questions in pharmacokinetics (Sheiner, 1984). The NONMEM approach (Sheiner et aI, 1972; 1977), currently the mostsatisfactory method of population pharmacokinetic data analysis is utilised in this study. / Thesis (M.Pharm.)--University of Durban-Westville, 1989.
2

Pharmaceutical availability on newly formulated oral sustained release pellets containing the antihistamine, chlorpheniramine maleate.

Mathir, Zohra Mohamed. January 1991 (has links)
The main objective of the present study was to determine the feasibility of obtaining aqueous polymer-coated pellet formulations using EudragitR NE 30 D dispersion and chlorpheniramine maleate as the model drug. Many factors influence the rate of drug release from coated beads including, the substrate, the coating formulation and the coating process. A drug release profile that was comparable to that of the reference standard, DykatussR Capsules was obtained with a formulation employing 8.3% EudragitR NE 30 D, 0.5% talc and 1% polyethylene glycol. In vitro dissolution tests on this formulation showed drug release to be predictable, reproducible and independent of the dissolution methods or media. Short term storage confirmed the stability at room temperature (20°C) and low temperature (5C). Scanning electron micrographs of pellets stored at elevated temperatures i.e. 37°C with 80% relative humidity and 40°C illustrated the phenomenon of 'further gradual coalescence' which corresponded to the decrease in release of drug from the pellets. / Thesis (M.Sc.)-University of Natal, Durban, Westville, 1991.
3

Synthesis and evaluation of novel tetrahydroisoquinoline organocatalysts in asymmetric catalysis.

Naicker, Tricia. January 2012 (has links)
Organocatalysis has rapidly expanded in the last decade to encompass a wide variety of small organic molecules that are capable of either activating substrates or transforming them into more reactive forms. The aim of this study was to develop novel chiral organocatalysts based on the tetrahydroisoquinoline backbone and evaluate them on asymmetric reactions. Three organocatalytic modes of activation have been investigated for C-C bond forming asymmetric reactions. In chapter 2, for the first time organocatalysts bearing a secondary nitrogen within a cyclohexane ring were evaluated in the asymmetric Diels–Alder reaction. These catalysts were tested over a range of dienes and dienophiles and displayed promising chemical conversions of up to 100 % with up to 64 % ee when triflic acid was employed as the cocatalyst. Density functional theory computational studies and 2D NMR spectroscopy were used to determine the structure of the intermediate iminium ion formed between the most efficient catalyst and cinnamaldehyde. Chapter 3 includes a series of novel tetrahydroisoquinoline chiral N-oxide organocatalysts and their evaluation in the asymmetric allylation reaction of aromatic and α-β-unsaturated aldehydes with allyltrichlorosilane. The chiral homoallyl products were obtained with good chemical efficiency (up to 93 % yield) and high enantioselectivity (up to 91 % ee) under mild reaction conditions (23 °C). Chapter 4 is the simple and practical microwave-assisted synthesis of new tetrahydroisquinoline guanidine organocatalysts and their evaluation in the asymmetric Michael addition reaction of malonates and β-ketoesters with nitro-olefins. In addition, a novel microwave assisted procedure of introducing the guanidine unit onto amino amide derivatives is reported. The chiral products were obtained with quantitative chemical efficiency (up to 99 % yield) and excellent enantioselectivity (up to 97 % ee). Chapter 5 is a collection of all X-ray crystal structures that were published from novel compounds synthesized pertaining to Chapters 2-4, it contains 15 published crystal structures while Chapters 3-4 contain 3 other X-ray crystal structures. It should be noted that with the exception of the introduction and Chapter 4 (submitted for publication), the remaining chapters of this thesis have been published in international peer reviewed journals. In the next section (DECLARATION 2 – PUBLICATIONS) a precise description of my contribution to each of the publications/chapters is provided. / Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2012.
4

Antimicrobial and chemical analyses of selected bulbine species.

Mocktar, Chunderika. January 2000 (has links)
The use of plant materials for the treatment of various diseases is very common in African countries. As traditional medicine used by the rural people does not always have a proper scientific basis, research programmes have to be undertaken to evaluate their therapeutic efficacy and safety. In traditional African medicine various Bulbine species are used to treat a number of conditions including sexually transmitted diseases, wound infections, dysentery and urinary tract infections. The Bulbine species belong to the family Asphodelaceae. There are over fifty South African Bulbine species and they are mostly herbs. Their leaves are evergreen and succulent in appearance. Bulbine species have thick fleshy tuberous roots, are easy to grow, are able to withstand drought and heat and are able to grow in poor soil. There is very little documented information on the antimicrobial activity and chemical properties of the Bulbine species. Therefore research programmes of this nature have to be undertaken. Various Bulbine species, viz., B. natalensis Bak, B. frutescens Willd (yellow flowers), B. narcissifalia Salm Dyck, B. abyssinica A Rich and B. frutescens Willd (orange flowers) were collected. The plants were washed with tap water, air dried and separated into the different components. Each component was cut into small pieces and immersed in methanol: dichloromethane (1:1, v/v) for extraction. The organic solvent was decanted from the plant material and evaporated under reduced pressure. The resultant crude extracts were stored in glass vials in the freezer. In addition, the roots, stems and leaves of B. natalensis and B. frutescens (yellow flowers) were extracted aqueously. The crude organic and aqueous were subjected to various tests to evaluate their antimicrobial and cytotoxic potential. To evaluate their antibacterial activities, the Disk Diffusion and Bore Well Methods were employed. The crude extracts were tested against various pathogens implicated in wound and urinary tract infections and dysentery. In these experiments the Disk Diffusion Method produced better results than the Bore Well Method. The crude organic and aqueous extracts were found to be effective against many of the bacteria used in this study including K. pneumoniae, S. aureus, S. typhi and S. flexneri which are considered to be troublesome pathogens. The TLC bioassay was employed to evaluate the antifungal potential of the various crude extracts against Aspergillus and Penicillium and the Disk Diffusion and Bore Well methods were used to evaluate the antifungal potential of C. albicans. The Bulbine species displayed no antifungal activity against Penicillium and limited antifungal activity against Aspergillus. The two method used to evaluate the antifungal activity of. C albicans was chosen because C. albicans grows in a similar manner to bacteria on solid and liquid culture media. Only the root extracts of the two B. frutescens varieties were inhibitory to C. albicans. The Brine Shrimp Bioassay was used to ascertain the cytotoxic potential of the crude extracts. The majority of the extracts were cytotoxic at the most concentrated dilution (i.e., dilution 1) but not cytotoxic at the lower dilutions. The only extracts that were not cytotoxic at the most concentrated dilution were the organic extract of the root of B. frutescens (yellow flowers), the organic extract of the root of B. narcissifolia and the organic extract of the leaf of B. abyssinica. TLC and column chromatography was carried out to evaluate the chemical composition of the Bulbine species. The TLC indicate that this technique could be a valuable tool in identifying the different species in the genus Bulbine. Column chromatogram was carried out on the extract which displayed a significant amount of antibacterial activity against the bacteria used in this study. The stem extract of B. natalensis was chosen for further analysis. The stem extract was fractitioned into different fractions but unfortunately none of the chemical component could be identified. According to the results obtained in this study, there is considerable scope for further studies of this genus. / Thesis (M.Med.Sc.)-University of Durban-Westville, 2000.
5

An assessment of the level of knowledge of diabetics and primary health care providers in a primary health care setting : on diabetes mellitus.

Moodley, Lushendran Manikum. January 2006 (has links)
Thesis (M. Med. Sc.)-University of KwaZulu-Natal, 2006.
6

HIV and the metabolic syndrome.

Bryant, Lynda P. January 2008 (has links)
Abstract not available. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, 2008.
7

Pharmacological effects of Hypoxis hemerocallidea Fisch. & C. A. Mey. (Hypoxidaceae) Corm ("African Potato") aqueous extract on some mammalian extra-vascular smooth muscles in vitro.

Nyinawumuntu, Agatha. January 2009 (has links)
Extracts of Hypoxis hemerocallidea corm (African potato) are commonly used by some traditional health practitioners in KwaZulu-Natal Province of South Africa for an array of human ailments. This study was, therefore, undertaken to investigate the GIT spasmolytic, bronchospasmolytic, uterolytic and vasa deferentia relaxant effects of Hypoxis hemerocallidea corm aqueous extract. Respectively, these effects were determined on both naive and spasmogenevoked contractions of the guinea-pig and rat isolated ileum, trachea, uterine horns and the vas deferens in vitro. Healthy, young adult, male and female Dunkin-Hartley guinea-pigs (300-400g) and Wistar rats (250-350g) were used in this study. The isolated tissues were prepared and mounted in Ugo Basile organ-baths under normal physiological conditions. After an equilibration period of 30-45 minutes, the isolated smooth tissue segments were challenged with graded concentrations of Hypoxis hemerocallidea corm aqueous extract, and/or reference drugs. Changes in tension developed by the muscle preparations (relaxations and contractions) were recorded isometrically by means of Ugo Basile's force-displacement transducers and pen-writing 'Gemini' recorders. Relatively low to high concentrations of Hypoxis hemerocallidea corm aqueous extract (APE, 25-400 mg/ml) produced dose-dependent and significant (p<0.05) relaxations of the guinea-pig ileum, and the uterine horns taken from non-pregnant rats, as well as on spasmogenprovoked contractions of stilboesterol-primed, oestrogen-dominated, non-pregnant rats in a concentration-related manner. Potassium chloride (40 mM)-induced contractions of uterine horns, ACh (0.1-3.2 ug/ml)-induced increases in the amplitude of contractions of the guinea-pig ileum, as well as noradrenaline (0.2-1.6 ug/ml)-induced increases in the amplitude of contractions of the male rat isolated vasa diferentia, were significantly (p<0.05-0.001) reduced or abolished by bathapplied APE (25-400 mg/ml). Relatively low to high concentrations of the extract (25-400 mg/ml) caused concentration-dependent increases in the relaxations of the guinea-pig isolated tracheal smooth muscles. Inhibitions of ACh (0.1-3.2 ug/ml)-induced contractions of the guineapig isolated ileum probably suggests possession of antidiarrhoeal activity of APE. Results of this study show pronounced relaxant effects of Hypoxis hemerocallidea corm aqueous extract on guinea-pig vas deferens. The study also lends pharmacological credence to the folkloric, ethnomedical uses of APE as a natural antenatal remedy for threatening abortions, as an antidiarrhoeal remedy, and as a bronchorelaxant. The precise mechanisms of APE action on the smooth muscles could not be established in the present study. However, the uterolytic action of the corm's extract is unlikely to be mediated via ^-adrenoceptor stimulation, but probably mediated through a non-specific spasmolytic mechanism. / Thesis (M.Pharm.)-University of KwaZulu-Natal, 2009.
8

A retrospective analysis of subjects who have approved gastro-oesophageal reflux disease (GORD) from a private medical aid fund.

Suleman, Aisha Bebe. January 2006 (has links)
Abstract not available. / Thesis (M.Med.Sc.-Pharm.)-University of KwaZulu-Natal, 2006.
9

Multipolymeric monolayered mucoadhesive films for drug therapy.

Perumal, Velisha Ann. January 2007 (has links)
The use of the oral cavity membranes as sites of drug administration has been a topic of increasing interest for the past decade. The buccal route, in particular, offers several advantages over the per oral route and may prove to be a viable alternative to other routes for drug delivery, as it bypasses hepatic first pass metabolism, thereby improving the systemic bioavailability of the administered drug. A controlled drug release formulation may further enhance the therapeutic efficacy of a buccal drug delivery system. Propranolol HCI (PHCI), a non-selective p-blocker, primarily advocated in the treatment of hypertension, has a short half-life (3 - 6 hours) and is also subjected to extensive hepatic first-pass metabolism following oral administration, resulting in a low oral bioavailability, therefore rendering it an ideal candidate for buccal drug delivery. For optimal controlled release and mucoadhesivity of a buccal delivery system containing PHCI, the blending of polymers and drug of opposing solubilities may be required for the formation of monolayered films. The aim of this study was therefore to formulate and characterise multipolymeric monolayered mucoadhesive films containing drug and polymer/s of opposing solubilities for the buccal delivery of PHCI. First, preparation parameters for the formation of monolayered multipolymeric films (MMFs) and homopolymeric PHCI films comprising drug and polymer/s of opposing solubilities, i.e. Chitosan (CHT) and Poly(D,L-lactide-co-glycolide) (PLGA) by an emulsification/casting/solvent evaporation method were investigated. MMFs could be prepared at all homogenisation speeds (6000, 9000, 12000, 15000 rpm) and times (1, 5, 15, 25 minutes). The films showed micromatrices embedded in the film matrix due to the inclusion of the PLGA polymer. Increased homogenisation speed and time resulted in a reduction in the size of the micromatrices. Phase separation occurred at temperatures below 20 °C. Emulsifiers employed in the study (Poly(vinylalcohol) (PVA) and Tween 80®) adversely affected the morphology and appearance of the film and were therefore not considered feasible for inclusion in the formulation. The preparation parameters identified for emulsification without phase separation and the subsequent generation of monolayered films, without phase separation during solvent evaporation and drying, were emulsification at 20 °C and homogenisation at 9500 rpm for 15 minutes. It was discovered through preliminary investigations and a comprehensive literature search that the conventional film casting method of film preparation suffered from poor drug content uniformity. To address this problem of non-uniformity, a specially designed silicone-molded tray (SMT) for film casting was prepared and evaluated in terms of enhancing drug content uniformity. These investigations confirmed that the SMT with teflon-coated perspex inserts provided a reproducible method for the preparation of both homopolymeric and multipolymeric (including drug and polymers of similar and opposing solubilities) films that met drug content uniformity requirements (assay values were within 92-107.5%) and also reduced the variability in mucoadhesivity (p=0.2922), drug release [fi values = 92.76, 90.99 and 86.06) and film thickness for all three trays. The final phase of this study involved the identification of a suitable polymeric blend for the preparation of MMFs comprising hydrophilic and hydrophobic polymers for the controlled buccal delivery of PHCI and subsequent characterisation of these films in terms of their physicochemical/mechanical properties. Initial investigations of different polymers for the formation of homopolymeric films showed that the combination of drug and polymer/s of opposing ionic states was not possible due to complexation. PHCI film formation as homopolymeric films was achievable with hydrophilic polymers, Hydroxypropylmethylcellulose (HPMC) and CHT, and hydrophobic polymers, Ethylcellulose (EC) and Eudragit® RSI00 (EUD100). It was also found that combining PHCI, a hydrophilic drug, with a hydrophilic polymer (CHT or HPMC) failed to retard drug release (> 80% at 1 hour), whilst the release of PHCI from a homopolymeric film comprising a hydrophobic polymer (EC or EUD100) was retarded. A PHCIiEUDlOO (1:10) film provided controlled release but was too retarded (< 67% at 8 hours) for the purposes of this study. Hence, the polymeric content of the formulation was altered by the addition of a hydrophilic polymer CHT, to obtain the desired controlled release profile. A PHCI:EUD100:CHT (1:10:0.5) polymeric blend (MMF) was found to be suitable for the controlled release of PHCI and was reproducible in terms of drug content uniformity (p=0.1964), drug release [h values = 83.18; 82.03 and 71.19) and mucoadhesivity (p=0.9971). Drug release followed Higuchi's square-root model (r2=0.9426). Scanning electron microscopy revealed that the addition of CHT to the PHCI:EUD100 (1:10) film formulation rendered it more textured, which contributed to the faster drug release observed with the PHCI:EUD100:CHT (1:10:0.5) MMF. Swelling and erosion studies indicated that maximal swelling of the films occurred after 1 hour and 28.26% of the film eroded during the 8 hour test period. The system also demonstrated acceptable mucoadhesivity and mechanical properties. The surface pH of the films also remained constant at neutral pH throughout the study. The data obtained in this study confirmed the potential of this multipolymeric monolayered film system as a promising candidate for the controlled buccal delivery of PHCI. Key words: Films; Buccal; Multipolymeric; Mucoadhesive; Controlled drug release; Propranolol HCI / Thesis (M. Med. Sc.) - University of KwaZulu-Natal, 2007.
10

The pharmacokinetics of phenobarbitone in fasting and non-fasting dogs.

Thurman, Graham Duncan. January 1990 (has links)
Practicing clinical veterinarians in large companion animal practices are often faced with the phenomena of epileptic seizures which occur commonly in dogs. The high incidence of non-responsive cases is often frustrating, and the literature offers incomplete, conflicting and often inaccurate information. The concept of therapeutic anti-epileptic drug concentration monitoring, as applied in man as an aid to treatment, appears attractive in order to provide an improved service to the patient and client. An investigation into the pharmacokinetics of phenobarbitone, particularly at steady state, became necessary in order to interpret the application of drug serum concentration monitoring. The trend of veterinarians to extrapolate human kinetics to dogs is common and unsound. This study was an attempt to identify the similarities and dissimilarities between the pharmacokinetics of dogs and humans. No literature was available, both for man or animal, on the effect of food on the absorption of phenobarbitone. As dog owners frequently have to administer oral medication in food, this was an important factor to examine. The kinetics of the drug was determined in a group of epileptic dogs in order to provide a possible base-line therapeutic regime on commencement of treatment, and the practical application of therapeutic drug monitoring in order to individualize and improve response to treatment was explored. / Thesis (M.Sc.)-University of Durban-Westville, 1990.

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