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Class of 2011 Abstract / OBJECTIVES: To determine the solubility and stability of hydrocortisone in a ‘magic mouthwash; suspension. METHODS: A literature review was conducted to establish the most common ingredients in a ‘magic mouthwash’ suspension It was decided that the test suspension would consist of 75% commercially available diphenhydramine solution, 12.5% nystatin suspension (100,000 units/ml) , and 12.5% lidocaine solution (2% lidocaine). Powdered hydrocortisone was then added to the test suspensions at different concentrations and stored at 27C, 38C, and 48C. Aliquots were taken from each of the test samples at the time of compounding and at 4, 7, 13, 19, and 26 days to be analyzed by HPLC for degradation of hydrocortisone and percent hydrocortisone in suspension. RESULTS: At 27C, 98.5% of hydrocortisone was recovered after 26 days, versus 33.7% at 38C, and 7% at 48C. The solubility of hydrocortisone in the suspension was higher at higher temperatures, with 82% in solution at 48C, 70% at 38C, and 38% at 27C. CONCLUSION: The amount of hydrocortisone recovered deteriorated over time and at higher temperatures, and solubility of hydrocortisone in the suspension was greater at higher temperatures.

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

No description available.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves [126]-139).

Os glicocorticóides são muito utilizados na clínica veterinária por serem potentes inibidores da resposta inflamatória. São encontrados em muitas preparações tópicas, sozinhos ou combinados com outros medicamentos e estão presentes, principalmente, em produtos destinados ao uso otológico. Mesmo quando aplicados topicamente, sabe-se que existe certo grau de absorção. Com a disponibilidade de novos glicocorticóides sintéticos mais potentes, vem sendo sugerido recentemente, a ocorrência de hiperadrenocorticismo iatrogênico em pequenos animais. Com a finalidade de se testar a hipótese que a utilização de preparações otológicas contendo glicocorticóides podem ocorrer em efeitos sistêmicos, o presente estudo avaliou três antiinflamatórios esteroidais comumente utilizados no tratamento de otite em cães e gatos, quais sejam a hidrocortisona, a betametasona e a triancinolona. Para tanto, ratos foram tratados tópicamente, via auricular, a cada 12 horas, durante 7, 14 e 21 dias, com os fármacos descritos acima. Utilizamos o edema de pata induzido pela injeção de carragenina como forma de avaliar a existência de níveis efetivos de antiinflamatórios circulantes. Ainda, foram avaliados vários parâmetros tais como variação de peso corpóreo, peso relativo de baço e adrenais, hemograma completo, índice de proliferação de linfócitos e fagocitose e burst oxidativo realizados por neutrófilos circulantes. Além disso, foi avaliado o nível de corticosterona plasmática nos animais tratados com glicocorticóides tópicos. O tratamento tópico com antiinflamatórios esteroidais levou a redução no volume de edema inflamatório, mais evidente com a triancinolona. De forma geral, houve queda no ganho, ou mesmo perda de peso corpóreo durante o tratamento tópico com os antiinflamatórios esteroidais empregados. Em alguns casos, essa redução de peso corpóreo foi acompanhada de diminuição do peso relativo do baço e adrenais, particularmente com a betametasona. A principal alteração observada no hemograma foi leucopenia, mais evidente com a triancinolona. Houve redução dos níveis plasmáticos de corticosterona, mais duradoura com a betametasona. Os tratamentos tópicos causaram discreta redução na intensidade e percentual de fagocitose realizada por neutrófilos circulantes, bem como na produção de espécies reativas de oxigênio. O estudo aponta que glicocorticóides tópicos comumente empregados na terapêutica veterinária podem ser absorvidos, na dependência da molécula empregada e de seu tempo de utilização, causando alterações sistêmicas relevantes já após 7 dias de tratamento. Sugerimos uma maior cautela e acompanhamento veterinário dos pacientes nos casos que haja necessidade de emprego de tais medicamentos por períodos prolongados. / Glucocorticoids are commonly employed in veterinary practice because they are potent inhibitors of the inflammatory response. They are present in many topical formulations, alone or combined with other active compounds, particularly in otic ointments. Even when applied topically, certain degree of absortion is known to occur. Following the availability of novel, more potent synthetic steroidal anti-inflammatory drugs, cases of iatrogenic hyperadrenocorticism have been suggested. Aiming on testing the hypothesis that glucocorticoid-containing otic ointments may lead to systemic effects, we employed three different synthetic glucocorticoids widely used for the treatment of otitis in small animals (hydrocortisone, betamethasone, and triamcinolone) our study Rats were treated topically on their ears, every 12 hours, for 7, 14, or 21 days with the drugs described above. We first employed carrageenan-induced paw edema in order to evaluate the presence of effective levels of circulating anti-inflammatory drugs. We also evaluated several parameters such as change in body weight, relative weight of spleen and adrenal glands, complete hemogram, proliferation index of lymphocytes, and phagocytosis and oxidative burst performed by circulating neutrophils. Moreover, we assessed the plasmatic levels of corticosterone in rats treated topically with anti-inflammatory steroids. Topical treatment led to a reduction on the volume of the inflammatory edema induced by carrageenan, more evident following triamcinolone. Altogether, rats treated with these molecules ceased to gain, or lost weight on the course of the experiment. In some cases, such reduction was accompanied by a decrease on the relative weight of the spleen and adrenal glands, particularly after betamethasone. The most commonly observed change in the hemogram was leucopenia, evident following triamcinolone. We found reduced levels of circulating corticosterone, more persistent after betamethasone. Topically applied glucocorticoids caused a discrete reduction in the intensity and percentage of phagocytosis by circulating neutrophils, and a reduction on the oxidative burst performed by these cells. This study shows that topical steroidal anti-inflammatory drugs, so commonly employed in veterinary practice, can be absorbed, depending on the molecule and duration of treatment, leading to systemic effects, which are already relevant after 7 days. Based on our findings, we suggest caution and a close follow-up by a qualified veterinarian whenever a long-term therapy based on these molecules and route of administration is required.

Introdução - A menopausa é um processo natural do envelhecimento feminino que se associa a uma sucessão de eventos com repercussões biológicas e psicossociais, dentre eles o estresse; definido como um estado de tensão que ocasiona a desordem na homeostase do organismo repercutindo na qualidade de vida da mulher. Objetivo - Investigar a presença do estresse em mulheres na menopausa e correlacionar com a concentração de cortisol, bem como associar o estresse com os sintomas musculoesqueléticos. Métodos - Estudo analítico transversal que investigou o estresse por meio do Inventário de Sintomas de Stress (ISSL) em 1200 mulheres da plataforma PROSAPIN cadastradas na Saúde da Família de Pindamonhangaba-SP. O método consistiu na aplicação de um questionário auto-referido. Os fatores associados foram investigados por meio de informações sócio-demográficas, hábitos de vida, história ginecológica e obstétrica, morbidades, dados antropométricos, laboratoriais e uso de medicamentos. Foram feitas análises bivariadas e multivariadas, utilizando um intervalo de confiança de 95 por cento . Testes de correlação - kappa e testes diagnósticos foram realizados comparando o estresse avaliado por questionário com a concentração do cortisol, no programa Stata. Resultados - O ISSL detectou estresse em 60,9 por cento das mulheres (IC95 por cento : 57,7 por cento a 64,1 por cento ) e o cortisol indicou a presença do estresse em 10,4 por cento (IC95 por cento : 8,1 por cento a 12,7 por cento ), não houve concordância entre a percepção do estresse e a mensuração do cortisol (k= 0,029). Os fatores associados à percepção do estresse foram: incontinência urinária, presença dos sintomas climatérios e de dor, qualidade do sono, depressão, acidente vascular encefálico e não ser cuidador de parente e possuir renda familiar. Os fatores associados ao cortisol foram: ansiedade, a falta de vitamina D, praticar atividade física e morar com ate três pessoas. Houve associação entre o estresse e os sintomas musculoesqueléticos, sobretudo com as regiões corporais do ombro, coluna lombar e joelho. Conclusão - A prevalência da percepção do estresse foi alta abrangendo mais da metade das mulheres, não houve correlação entre as medidas. Houve forte associação principalmente com a incontinência urinária, sintomas climatérios e musculoesqueléticos, ansiedade e falta de vitamina D. Sendo assim, considera-se que a presença do estresse intervém negativamente na qualidade de vida das mulheres na menopausa. / Introduction - Menopause is a natural female ageing.This process has been asssociated with a series of events like biological and psychosocial effects. Ageing process is associated with a series of events with biological and psychosocial effects, including stress defined as a state of tension causes of disorder in homeostasis reflecting on the quality of life women. Objective- Investigating the presence of stresses during its climacteric women the correlation with the concentration of cortisol and stress. It was associated with musculoskeletal symptoms. Methods -These methods were analyzed in studies cross analytical that investigated stress. Through the Stress Symptom Inventory (ISSL) in 1200 women PROSAPIN platform registered in the Health Pindamonhangaba-SP. The method consisted of applying a self-reported questionnaire. The associated factors were investigated by socio-demographic, lifestyle, gynecological and obstetric history, comorbidities, anthropometric, laboratory data and use of medications. They were made bivariate and multivariate analyzes using 95 per cent confidence interval. Correlation tests using measure of agreement (kappa) and diagnostics. This diagnostics were performed comparing the stress assesociate with this questionnaire by the concentration of cortisol in the Stata program. Results - The ISSL stress detected in 60,9 per cent of women (95 per cent CI: 57.7 per cent to 64.1 per cent ) and cortisol indicated the presence of stress in 10,4 per cent (95 per cent CI: 8,1 per cent to 12,7 per cent ), there was no correlation between perceived stress and the measurement of cortisol (k = 0,029). They factors were associated with perceived stress like : urinary incontinence, presence of climacteric symptoms and pain, sleep quality, depression, stroke and not be related to caregiver and have family income. Factors associated with cortisol were: anxiety, lack of vitamin D, physical activity and live with up to three people. Conclusion - The prevalence of perceived stress was high covering more than half of women, there was no correlation between measures. There were a strong association mainly with urinary incontinence, climacteric and musculoskeletal symptoms, anxiety and lack of vitamin D. Therefore, it is considered that the presence of stress intervenes negatively on the quality of life during the climacteric.