The investigations in this dissertation have been 'conducted to investigate the formulation and analysis of a paediatric amoxycillin suppository. The oral administration of antibiotics to young children can at times be roblematic. Compliance is sometimes poor because of a sore throat, nausea, vomiting, a high fever or a dislike for the taste or smell of the medicine:- In-such cases the rectal administration of an antibiotic could provide an alternative route of administration that avoids some of the problems that affect oral administration. Difficulties associated with rectal administration are bioavailability, local irritation, acceptability to patients and rejection of the dosage form. Few data, however, are available on the usefulness in children of suppositories in general, and antibiotic suppositories in particular. The areas of investigation have included the formulation of an amoxycillin suppository in various fatty bases, the quantitation of amoxycillin in both aqueous solution and human serum, assessment of stability of amoxycillin in stored aqueous and biological samples, in vitro drug release testing of suppositories, and bioavailability and pharmacokinetics following administration to human subjects of capsule, suppository, oral suspension and rectal suspension dosage forms. Suppositories containing 250 mg amoxycillin were prepared in theobroma oil and in the semisynthetic bases Witepso[ W35, Suppocire A32, Novata BD and Novata 299. The in vitro release characteristics of amoxycillin from these lipophilic suppository formulations were investigated using the USP rotating basket method. The dissolution of a drug from a solid dosage unit is an important parameter affecting drug bioavialability. High Performance Liquid Chromatography (HPLC) was used as the main analytical technique. An original HPLC method for analysis of amoxycillin in aqueous solution, using ultraviolet detection at 230 nm was develcfped. The validated method was a~plied to the determination of the stability of aqueous amoxycillin solutions, and was utilized to determine the amount of drug released during dissolution testing. Differential scanning calorimetry (DSC) is a technique commonly used in preformulation studies. Dissolution testing was used in conjunction with DSC to select a suppository base suitable for formulation with amoxycillin trihydrate. An HPLC method for analysis of amoxycillin in human serum using UV detection at 230 nm is presented. The method involves a solid phase extraction procedure followed by chromatography on a reversed phase column. The limit of sensitivity of 0.3 ILg/mL in serum is sufficiently sensitive to monitor serum concentrations of amoxycillin in humans after the administration of a single 250 mg oral dose. Pharmacokinetic parameters were calculated from data obtained following the administration of a capsule and oral suspension. These parameters were consistent with previously published results. Following administration of a lipophilic suppository and a rectal suspension, to human volunteers, it was concluded that amoxycillin trihydrate is not readily absorbed from the rectum. Further investigations into the modification of the suppository dosage form with absorption enhancers to improve rectal absorption of amoxycillin, as well as elucidation of the mechanism of absorption of the drug, could assist in improving this formulation so that it is suitable for paediatric use.

University of Macau / Institute of Chinese Medical Sciences

Part I. Following a general historical review of the development of drug targeting, critical evaluations were made of current targeted drug delivery systems. Based on the results shown by previous studies, magnetic albumin microspheres containing adriamycin is one of the most promising targetable delivery systems for the treatment of solid tumors. It was also apparent that the pharmacokinetics of drugs associated with magnetic albumin microspheres had not been determined. A systematic study of the multiple variables involved in albumin microsphere preparation was completed to identify to what extent these variables affected the microsphere size distribution. The results of this investigation led to an optimal method of microsphere preparation. Information obtained from the above studies was applied to the production of magnetic albumin microspheres containing adriamycin suitable for in vivo use. The problems of separation and quantitation of adriamycin and adriamycinol in biological matrices were investigated using ion-pairing high pressure liquid chromatography. An optimized chromatographic system was presented for the analysis of these compounds in rat serum and tissues. The disposition of adriamycin following administration as magnetic albumin microspheres and as a solution was studied by monitoring adriamycin concentrations in multiple rat tissues for forty-eight hours after administration. The magnetic dosage form was targeted to a predefined tail segment with a magnetic field strength of 8000 G applied for 30 min after dosing. A physiological pharmacokinetic model was used to describe the disposition of adriamycin after both dosage forms. The model developed following adriamycin administration as a solution served as the foundation for the model for adriamycin when it was administered as the magnetic dosage form. Part II. The present investigation was designed to characterize the kinetics of ibuprofen in plasma and synovial fluid, which in the past, has been flawed by inadequate study protocols. After administration of a single dose and at steady-state, ibuprofen concentrations were measured simultaneously in plasma and synovial fluid obtained from eight patients with rheumatoid arthritis. The extent of accumulation of ibuprofen in each fluid was determined. The degree of ibuprofen protein binding in plasma and synovial fluid was also determined and related to its kinetic behavior.

No description available.

No description available.

No description available.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg in partial fulfillment of the requirements for the degree of MSc (Dent) / A comparison of radiation doses to selected vital organs in the maxillo-facial region at three different settings on the Galileos cone-beam computed tomography (CBCT) machine in the Wits Dental Hospital, was conducted with the courtesy of the Department of Medical Physics of the Charlotte Maxeke Johannesburg Academic Hospital. The study made use of the RANDO phantom and TLD- 100 detector chips, which provided detailed mapping of the dose distribution from the Galileos CBCT machine. Sixty-two Sanford® lithium fluoride dosimeters- (TLD- 100) were irradiated using a calibrated known x-ray source after having undergone a recommended annealing cycle. The data showed great consistency in the results. Association between the different imaging modalities was further investigated using Kruskal-Wallis equality-of-populations rank test and Chi-squared test. A p-value of <0.05 was considered statistically significant. Since there do not appear to be major differences between the radiation doses for the different settings of the Galileos CBCT machine, the author recommends the use of the combined setting at all times for optimum image quality.

Degree of Master of Science in Dentistry by coursework and dissertation A research report submitted to the Faculty of Health Sciences, University of the Health Sciences. University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Science in Dentistry Johannesburg, 2014 / Introduction: Dental Cone beam CT has encountered great success in diagnostics and treatment planning in dentistry. However, it makes use of ionizing radiation. Lots of concern on the effects of x-rays on vital organs of the head and neck region has been raised. Clarity on the amount of radiation received on these specific organs will be a contribution to a better use of the emergent technology. Aim: The aim of this study is to determine the potential dose of radiation received on the eye and thyroid and to quantify the amount of potential scatter on the gonads during CBCT examinations. Material and Methods: Calibrated Lithium- Fluoride thermoluminescent dosimeters were inserted inside an anthropomorphic phantom, on sites of the eye, thyroid and the gonads. After its submission to a CBCT examination, using the high and standard resolution for a similar scanning protocol, the dose of radiation received on each organ was calculated according to the ICRP guidelines. Results: An equivalent dose of 0.059 mGy was calculated for the eye. Compared to the threshold dose of 0.5 Gy fixed by the ICRP 2007, this can be considered as relatively low. The thyroid with an effective dose of 23.5 μSv represented 20% of the full body effective dose existing in literature. The gonads absorbed an effective dose of 0.05 μSv, which was considered as negligible. Conclusion: The doses calculated were considered as relatively low. However, dentists must be aware of risks of cumulative exposure. Therefore adherence to the ALARA principle and consideration of clinical indication for CBCT remain a priority.

No description available.

Terahertz radiation refers to a specific part of the electromagnetic spectrum, flanked by microwave and infrared radiation at the higher and lower frequency end respectively. This thesis is about the development of applications using a new source of pulsed, coherent light for the physical characterisation of solids in the pharmaceutical setting. Terahertz radiation has excellent potential in the advancement of science but is, as yet, largely unexplored. Recent developments in semiconductor physics have made it possible to provide light at terahertz frequencies (a frequency of 1 THz equals a wavelength of 0.3 mm) in a relatively easy way. Light located in this range of the electromagnetic spectrum was very difficult to generate previously. It has unique properties in that it is possible to extract the full spectroscopic fingerprint of the materials by looking at the frequency response of the terahertz pulse. Here, vibrations of the whole molecule are probed rather than just the vibrations of single functional moieties within a molecules as is the case in infrared spectroscopy, which makes terahertz spectroscopy a very powerful tool for the analysis of the complex solid-state materials properties. In addition to structural information it easily penetrates through most plastics and polymeric materials used as excipients for pharmaceutical tablets. It is therefore especially useful for non-destructive imaging applications. At the example of polymorphic phase transitions, dehydration processes and crystallization experiments from the amorphous phase the potential of terahertz spectroscopy for pharmaceutical analysis was systematically investigated. In addition, a novel concept for using terahertz radiation in structural imaging of pharmaceutical dosage forms was developed. The technology, thus far predominantly used for the analysis of inorganic materials and semiconductors in particular, is now mature enough for its application to a wider field and to help with the understanding of fundamental and exciting new challenges at the interface between physics and the life sciences. Together with a comparison of this new technology to the established techniques in physical characterisation an initial attempt to understand and interpret the spectral information provided is presented. The potential for future applications is discussed.