Two possible variables of the McKenzie/Stoughton blanching assay, namely amount applied to the test site and occlusion time have been investigated. Subsequently, two topical steroid preparations, Synalar cream (0,025% fluocinolone acetonide) and Betnovate cream (0,1% betamethasone 17-valer ate) were extemporaneously diluted with five and six placebo bases respectively. Taking cognizance of the two possible variables, these diluted preparations were assessed in vivo using a modified version of the McKenzie/Stoughton blanching assay for blanching activity over a 14 month period. It was found that the base E45, which is slightly alkali, had the greatest effect on both preparations. In the case of betamethasone 17-valerate this base c aused the conversion to the less active isomer, betamethasone 21-valerate whereas at the end of the 14 month test period it was found that the Synalar/E45 dilution contained no fluocinolone acetonide. Quantitative analysis of all the diluted preparations by high performance liquid chromatography using a reverse-phase system was performed. The data obtained f r om the systematic stUdies of the effects of varying concentrations and occlusion times were presented at the Eleventh National Congress of the South African Pharmacological Society. / KMBT_363 / Adobe Acrobat 9.53 Paper Capture Plug-in

M.Tech. / Purpose: This study aims to compare the effects of spinal manipulative therapy to the lumbar spine and/or pelvis, and spinal manipulative therapy to the lumbar spine and/or pelvis in conjunction with the application of transcutaneous flurbiprofen patches in the treatment of sub-acute/chronic mechanical low back pain with regards to pain, disability and lumbar spine and pelvic range of motion. These effects were based on a questionnaire consisting of a Numerical Pain Rating Scale, and an Oswestry Low Back Pain and Disability Questionnaire, and on lumbar spine range of motion (ROM) readings taken using a digital inclinometer. The questionnaire was completed and the ROM readings taken prior to treatment on the first, fourth and seventh consultations.

Graduation date: 1992

The objective of this research is the development of an electrically active microneedle array that can deliver biomolecules such as DNA and drugs to epidermal cells by means of electroporation. Properly metallized microneedles could serve as microelectrodes essential for electroporation. Furthermore, the close needle-to-needle spacing of microneedle electrodes provides the advantage of utilizing reduced voltage, which is essential for safety as well as portable applications, while maintaining the large electric fields required for electroporation. Therefore, microneedle arrays can potentially be used as part of a minimally invasive, highly-localized electroporation system for cells in the epidermis layer of the skin. This research consists of three parts: development of the 3-D microfabrication technology to create the microneedle array, fabrication and characterization of the microneedle array, and the electroporation studies performed with the microneedle array. A 3-D fabrication process was developed to produce a microneedle array using an inclined UV exposure technique combined with micromolding technology, potentially enabling low cost mass-manufacture. The developed technology is also capable of fabricating 3-D microstructures of various heights using a single mask. The fabricated microneedle array was then tested to demonstrate its feasibility for through-skin electrical and mechanical functionality using a skin insertion test. It was found that the microneedles were able to penetrate skin without breakage. To study the electrical properties of the array, a finite element simulation was performed to examine the electric field distribution. From these simulation results, a predictive model was constructed to estimate the effective volume for electroporation. Finally, studies to determine hemoglobin release from bovine red blood cells (RBC) and the delivery of molecules such as calcein and bovine serum albumin (BSA) into human prostate cancer cells were used to verify the electrical functionality of this device. This work established that this device can be used to lyse RBC and to deliver molecules, e.g. calcein, into cells, thus supporting our contention that this metallized microneedle array can be used to perform electroporation at reduced voltage. Further studies to show efficacy in skin should now be performed.

Transdermal drug delivery system has been limited to small and lipophilic drugs because skin has the intrinsic function to protect the body preventing entry of the external species into the body. In this thesis, two physical methods were studied to overcome the skin barrier in the controlled breakage of the skin barrier and to deliver macromolecules-based drugs through the skin; (1) polysaccharide dissolving microneedles and (2) micro thermal skin ablation. Polysaccharide dissolving microneedles system was designed to break the skin barrier in a minimized size with the mechanically poor material, to release them into skin with the dissolution of microneedles, and to deliver human growth hormone into the living hairless rats. Micro thermal skin ablation was designed to fabricate the device generating the energy impact with the basis of arc discharge, to transfer the energy impact on the skin, to remove stratum corneum selectively with three-dimensionally controlled manner, and to deliver hydrophilic macromolecules through skin.

Currently, biopharmaceuticals including vaccines, proteins, and DNA are delivered almost exclusively through the parenteral route using hypodermic needles. However, injection by hypodermic needles generates pain and causes bleeding. Disposal of these needles also produces biohazardous sharp waste. An alternative delivery tool called microneedles may solve these issues. Microneedles are micron-size needles that deliver drugs or biopharmaceuticals into skin by creating tiny channels in the skin. This thesis focuses on dissolving microneedles in which the needle tips dissolve and release the encapsulated drug or vaccine upon insertion. The project aimed to (i) design and optimize dissolving microneedles for efficient drug and vaccine delivery to the skin, (ii) maintain vaccine stability over long-term storage, and (iii) immunize animals using vaccine encapsulated microneedles. The results showed that influenza vaccine encapsulated in microneedles was more thermally stable than unprocessed vaccine solution over prolonged periods of storage time. In addition, mice immunized with microneedles containing influenza vaccine offered full protection against lethal influenza virus infection. As a result, we envision the newly developed dissolving microneedle system can be a safe, patient compliant, easy to-use and self-administered method for rapid drug and vaccine delivery to the skin.

Thesis (M.S.)--University of Michigan, 1983.

Thesis (M. Sc.)--Memorial University of Newfoundland, 1997. / Bibliography: leaves 95-108.

Orientadores: Maria Helena Andrade Santana, Maria Vitoria Lopes Badra Bentley / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Quimica / Made available in DSpace on 2018-08-04T23:17:39Z (GMT). No. of bitstreams: 1 Barbosa_RaqueldeMelo_M.pdf: 4198029 bytes, checksum: b5072f7f5d6c82c75879c1717e1946ed (MD5) Previous issue date: 2005 / Resumo: Resumo: Neste trabalho foi estudada a preparação e caracterização de lipossomas elásticos e elástico-magnéticos projetados para facilitar o transporte transdérmico de moléculas bioativas. Os lipossomas preparados foram do tipo unilamelar, compostos de dimiristoilfosfatidilcolina sintética (DMPC), fosfatidilcolina de soja hidrogenada ou fosfatidilcolina de ovo (PCovo) como componentes estruturais e dos tensoativos derivados do ácido láurico: 'C IND. 12¿¿E IND. 5¿ (polioxietilenoglicol-4-dilauril ester) PEG8L (polioxietilenoglicol-8-luril ester), PEG4DL (polioxietilenoglicol-8-dilauril ester), como componentes elásticos. As propriedades magnéticas foram adicionadas aos lipossomas através da incorporação da magnetita coloidal. A incorporação dos tensoativos nos lipossomos foi feita por dois procedimentos: durante a hidratação do filme lipídico ou por incubação com lipossomas pré-formados. Os lipossomas elásticos foram caracterizados através da quantificação do teor de fosfolipídios, diâmetro médio e distribuição de tamanhos, incorporação dos tensoativos, capacidade de permeação em membranas artificiais com poros de 50 e 30nm, elasticidade e estabilidade física de estocagem. Nos lipossomas elástico-magnéticos foi também caracterizada a incorporação da magnetita coloidal. Os resultados experimentais mostraram que a temperatura de transição de fases do fosfolipídio, a fluidez da bicamada lipídica produzida pela incorporação do tensoativo e a preservação da integridade da partícula foram fatores que determinaram o desempenho dos lipossomas elásticos na permeação através de membranas nanoporosas... Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital / Abstract: The purpose of this work was to study the preparation and characterization of elastic and elastic-magnetic liposomes designed to facilitate the transdermal transport of drugs. The prepared liposomes were unilamellar, composed by synthetic dymirystoylphosphatidylcholine (DMPC), hydrogenated soy phosphatidylcholine or egg phosphatidylcholine (PCegg) as structural components and by the derivative lauric acid surfactants: 'C IND. 12¿¿E IND. 5¿(polyoxyethylene-5-lauryl ether), PEG4L (polyethyleneglycol-4-lauryl ester), PEG4DL (polyethylenoglycol-4 dilauryl ester), PEG8L (polyethyleneglycol-8-lauryl ester) e PEG8DL polyethyleneglycol-8- dilauryl ester) as elastic components. Magnetic properties were added to elastic liposomes by incorporation of colloidal magnetite. The incorporation of surfactants to liposomes was done by two procedures: during hydration of lipid film or by incubation with preformed liposomes. The elastic liposomes were characterized through their phospholipid contents, mean diameter and size distribution, incorporation of surfactants, capability for permeation through artificial membranes containing 50 or 30 nm porous, elasticity and storage stability. The incorporation of colloidal magnetite was also characterized in elastic-magnetic liposomes. The experimental results show that the phospholipid phase transition temperature, the fluidity of the lipid bilayer generated by surfactant incorporation and the preservation of particle integrity were factors determining the performance of elastic liposomes on permeation through nanoporous membranes. In this context, DMPC and PCegg phospholipids and the surfactants PEG8L and PEG8DL were the best compounds... Note: The complete abstract is available with the full electronic digital thesis or dissertations / Mestrado / Desenvolvimento de Processos Biotecnologicos / Mestre em Engenharia Química

Ketoprofen is a potent non-steroidal anti-inflammatory drug which is used for the treatment of rheumatoid arthritis. The oral administration of ketoprofen can cause gastric irritation and adverse renal effects. Transdermal delivery of the drug can bypass gastrointestinal disturbances and provide relatively consistent drug concentrations at the site of administration. The release of ketoprofen from proprietary gel products from three different countries was evaluated by comparing the in vitro release profiles. Twenty extemporaneously prepared ketoprofen gel formulations using Carbopol® polymers were manufactured. The effect of polymer, drug concentration, pH and solvent systems on the in vitro release of ketoprofen from these formulations were investigated. The gels were evaluated for drug content and pH. The release of the drug from all the formulations obeyed the Higuchi principle. Two static FDA approved diffusion cells, namely the modified Franz diffusion cell and the European Pharmacopoeia diffusion cell, were compared by measuring the in vitro release rate of ketoprofen from all the gel formulations through a synthetic silicone membrane. High-performance liquid chromatography and ultraviolet spectrophotometric analytical techniques were both used for the analysis of ketoprofen. The validated methods were employed for the determination of ketoprofen in the sample solutions taken from the receptor fluid. Two of the three proprietary products registered under the same manufacturing license exhibited similar results whereas the third product differed significantly. Among the variables investigated, the vehicle pH and solvent composition were found have the most significant effect on the in vitro release of ketoprofen from Carbopol® polymers. The different grades of Carbopol® polymers showed statistically significantly different release kinetics with respect to lag time. When evaluating the proprietary products, both the modified Franz diffusion cell and the European Pharmacopoeia diffusion cell were deemed adequate although higher profiles were generally obtained from the European Pharmacopoeia diffusion cells. Smoother diffusion profiles were obtained from samples analysed by high-performance liquid chromatography than by ultraviolet spectrophotometry in both diffusion cells. Sample solutions taken from Franz diffusion cells and analysed by ultraviolet spectrophotometry also produced smooth diffusion profiles. Erratic and higher diffusion profiles were observed with samples taken from the European Pharmacopoeia diffusion cell and analysed by ultraviolet spectrophotometry. The choice of diffusion cells and analytical procedure in product development must be weighed against the relatively poor reproducibility as observed with the European Pharmacopoeia diffusion cell.