Thesis (M.S.)--University of Michigan, 1998. / Includes bibliographical references.

Thesis (doctoral)--Lunds Universitet.

Thesis (doctoral)--Lunds Universitet.

Thesis (M.S.)--University of Michigan, 1961.

Thesis (M.S.)--University of Michigan, 1971.

Orientador: Alberto Carlos Botazzo Delbem / Resumo: O objetivo do presente trabalho foi desenvolver metodologia para determinar a relação dose-resposta de produtos fluoretados utilizando esmalte bovino e modelo de ciclagem de pH. Os blocos de esmalte, previamente selecionados através de microdureza de superfície, foram submetidos ao tratamento diário com solução placebo e soluções de NaF a 275, 550, e 1100 ppm F. Foram realizados dois métodos in vitro de desafio cariogênico para verificar o potencial dos produtos fluoretados para inibir a perda mineral (Des>Re) e a capacidade para promover a remineralização (Re>Des). Fatores de influência nas lesões in vitro produzidas no esmalte de dente bovino, como tempo de desmineralização e pH, tempo de remineralização, composição das soluções desmineralizadoras e remineralizadoras, freqüência e tempo de aplicação das soluções fluoretadas e duração da ciclagem foram O alterados para o estabelecimento de metodologia sensível, a partir dos modelos de Ten Cate & Duijsters (1982) e Featherstone et al. (1986). Após, realizou-se o cálculo da variação da microdureza de superfície, percentagem de volume mineral e flúor presente no esmalte. Testes paramétricos e não-paramétricos e análise de regressão foram utilizados para determinar relação dose-resposta entre os tratamentos realizados. As modificações propostas proporcionaram padronização das metodologias atingindo um alto nível de precisão, evidenciando relação dose-resposta entre os tratamentos em termos de flúor presente no esmalte, microdureza de superfície e percentagem de volume mineral em secção longitudinal. / Abstract: The aim of the present study was to establish methodology for verification of fluoride product dose-response relationship using a bovine enamel and pH-cycling model. Enamel blocks, previously selected in regards to surface microhardness, were submitted to daily treatment with placebo and NaF solutions (275, 550 and 1100 ppm F). Two in vitro methods of cariogenic challenge were performed to verify the potential of fluoride products to inhibit mineral loss and the ability to promote remineralization. Factors influencing in vitro bovine enamel lesions (time and pH of demineralization, time of remineralization, composition of demineralization and remineralization solutions, frequency and time of application of treatment solutions, and pHcycling duration) were altered for the establishment of a sensitive methodology, based on the studies of Ten Cate & Duijsters (1982) e Featherstone et al. (1986). Then, surface microhardness changes, % mineral volume and enamel's fluoride were calculated. Parametric and non-parametric tests and regression analysis were applied to establish dose-response relationship among different treatment groups. The proposed models provided for improvement in standardization of methods leading to a higher level of precision, demonstrating dose-response between treatments in regards to enamel's fluoride, surface microhardness and % mineral volume. / Mestre

No description available.

Class of 2006 Abstract / Objectives: To assess perceived efficacy and patient satisfaction at a single point in time during a course of therapy with a compounded topical formulation containing at least ketoprofen in an anhydrous gel base. Methods: Patients aged 18 and older, currently using one of the topical pain relief compounds of interest obtained from Reed’s Compounding Pharmacy in Tucson, Arizona were recruited and then interviewed (in person or by telephone) for this study. Data collected during patient interviews were recorded on a form designed solely for the purposes of this study. Interview questions pertained to the nature of the participant’s pain, their assessment of their pain both before treatment with the medication of interest and at the time of the interview, frequency and duration of patient use of the pain relief gel, disclosure of any other pain relief medications the patient was using at the time, and their overall satisfaction with the medication. Results: Interviews were conducted with a total of 50 patients with chronic pain conditions representing several different etiologies and anatomical locations. The average pain assessment score at the time of the interview (representing perceived patient pain after use of the topical pain relief compound) was significantly lower than the average before treatment pain assessment score (p<0.001). After treatment with the gel had commenced, perceived pain scores dropped by average of 3.56 units (SD 2.28), or 44%. Increased frequency of application of the topical pain relief gel was not associated with greater pain relief or changes in overall patient satisfaction with the product. A longer duration of use of the topical pain relief was also not associated with greater pain relief or overall patient satisfaction with the product. Whether or not a patient utilized other pain relief medication(s) while undergoing treatment with the topical pain relief gel had no bearing on the assessment of their pain either before use of the gel or at the time of interview. The average overall patient satisfaction with the topical pain relief compound was rated at 6.6 out of a possible 10 units (SD 3.13). Thirty-six patients (72%) rated their satisfaction with the topical medication of interest with a satisfaction score of ≥ 6, 10 patients (20%) rated their satisfaction with a score of 10 (completely satisfied), and 6 patients (12%) rated their satisfaction with a score of 0 (not at all satisfied). It was observed that the lower the perceived pain assessment score at the time of the interview (after using the gel), the greater the patient satisfaction with the product. Additionally, patients were observed to be more satisfied with the product if the difference between their perceived pain assessment scores (before and after) was greater (i.e.: greater patient satisfaction with greater pain relief). Conclusions: Treatment of chronic pain with a topical pain relief compound containing at least ketoprofen in an anhydrous gel base is associated with patient satisfaction and perceived analgesic benefits. During the one-time interview, most patients reported a significant improvement in their pain relief, and the great majority of patients were very satisfied with the compounded topical treatment they received from Reed’s Compounding Pharmacy.

Magister Pharmaceuticae - MPharm / Background/Introduction: Atopic dermatitis (AD) is one of the most prevalent diseases worldwide. It is a rapidly growing field of study with several research avenues to explore its pathophysiology and to find innovative treatment and management regimens. Clinically, it is classified as a non-contagious, intensely pruritic, inflammatory, chronic skin disorder mediated by abnormalities associated with atopy. Symptoms include inflammation, redness, pain and a negative impact on the patient‘s overall quality of life. Chronic itching often leads to the formation of lichenified skin, which may increase the thickness of the epidermis and exacerbate the barrier function of the skin. AD is treated with topical corticosteroids which help to decrease inflammation. However, lichification of the skin may decrease the efficacy of topical dosage forms. Nanomedicine is a rapidly developing field where advances have been made using ethosomes for topical delivery. As such, corticosteroid loaded ethosomal formulations containing hydrocortiosone acetate (HCA) and betamethasone valerate (BMV) were developed and characterised to develop novel tools for topical drug delivery. Aim: This study aimed at developing corticosteroid loaded ethosomes as a pre-formulation component for inclusion in a topical dosage form. To date, no ethosmal formulation with HCA and BMV has been investigated for topical drug delivery. Method: Ethosomes were synthesised using the hot method and the cold method, a modified version of a double emulsion (o/w/o), solvent evaporation technique, as developed by Touitou et al, 2007.1 Ethosomes were prepared using fixed concentrations of either BMV or HCA (10 mg/ml), ethanol (30% v/v) and purified water (70% v/v) and were comminuted using bath sonication or mini-extrusion. Centrifugation and centrifugal drying were used to purify and isolate the ethosomes for solid state characterisation. The morphology was determined using Scanning electron microscopy (SEM). Ethosomes were characterised using: dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), hot stage microscopy (HSM), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The encapsulation efficiency (EE) and drug loading (DL) were determined using validated HPLC methods. Finally, the drug release was determined using Franz diffusion cells and mathematical models were fitted to the % cumulative release data to determine the release kinetics. Results: Ethosomes were assessed according to the following criteria for topical drug delivery which were determined using dynamic light scattering (DLS): Hydrodynamic diameter (HdD), ~ 200 nm, polydispersity index (PdI) < 0.5 and zeta potential (ζp) ± 30 mV. The optimum formulations contained phosphatidylcholine (PC) 50 mg/ml. Extrusion was found to be the best method for particle reduction based on the reproducibility of the results. The HdD was 163.8±31.99 and 147.7±19.91 for BMV loaded ethosomes and HCA loaded ethosomes respectively and both formulations had an acceptable PdI of 0.049 and 0.111, respectively. SEM analyses indicated that the ethosomes had a spherical shape. Encapsulation of the APIs was verified by the thermoanalyses and possible intermolecular interactions were identified using FTIR. BMV loaded and HCA loaded ethosomes had a respective EE of 74.57 % and 37.30 %, and a DL of 14.91 % and 7.46 %, respectively. The release kinetics best fit the Peppas-Sahlin model indicative of an anomalous non-Fickian diffusion coupled with polymer relaxation and zero order release. Conclusions: BMV and HCA loaded ethosomes for topical drug delivery were successfully synthesised and characterised. These novel nanoparticles have provided an array of avenues for further investigation and application in the topical delivery of corticosteroids

The need for a preventative agent to curtail the rampant spread of HIV, other STDs and mucosal pathogens is urgent. Topical microbicides based on amphiphilic compounds have been identified as an attractive means toward this goal. Novel dendritic methacrylate macromonomers––di-tert-butyl 4-(2-tert-butoxycarbonyl-ethyl)-4-[3-(2-methacryoloxyethyl)ureido]heptandioate (MI) and di-tert-butyl 4-(2-tert-butoxycarbonylethyl)-4-[3-methyl-3-(2-methacryoloxyethyl)ureido]heptanedioate (MIII)––were synthesized, characterized, and subsequently polymerized via conventional free radical polymerization in acetonitrile employing AIBN as an initiator. Methyl 3-mercaptopropionate (MMP), a chain transfer agent, was employed to target low molecular weight (<10,000 g/mol) polymers. Dendronized homopolymers were prepared from MIII with varying MMP concentrations (0–10 mol%). MALDI-TOF MS characterized the homopolymer prepared with 10 mol% MMP (Mn = 2,481 g/mol). In the presence of MMP, MIII (5 to 25 mol%) was copolymerized with alkyl (methyl, ethyl, and n-butyl) methacrylates. Copolymer composition correlated well with monomer feed; Mns of 3–10K g/mol were observed. Ionizable polymers were achieved via acidolysis with trifluoroacetic acid; significant increases in Tg were observed. For the copolymers, the Tgs of the acids increased as the copolymer composition increased in MIII. For the homopolymers, Tgs decreased with increasing MMP concentration. The solubilities of carboxylic acid functional polymers were studied in 5 w/v % aqueous triethanolamine (aq TEA) at a concentration of 12.5 mg/mL. Clear, homogeneous solutions of the deprotected macromonomer, MIII(OH), homopolymer, PMIII(OH), and MIII(OH)/MMA copolymer series were observed; copolymer solubility decreased as the aliphatic chain length of the alkyl methacrylate increased. The amphiphilic dendronized polymer series incorporates many features shown beneficial in the pursuit of effective antimicrobial agents: amphiphilicity, multiple anionic functional groups, a polymer backbone, and aqueous solubility. Additionally, biological selectivity (e.g. cytotoxicity) is expected to be tunable through the control of molecular weight, alkyl chain length (n*), copolymer composition, and molecular architecture. / Ph. D.