Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / O sucesso do tratamento terapÃutico depende da biodisponibilidade do fÃrmaco, que pode ser afetada pela presenÃa de alimentos. Este estudo teve como objetivo avaliar a influÃncia da alimentaÃÃo na biodisponibilidade de duas formulaÃÃes de venlafaxina, administrada em cÃpsulas de liberaÃÃo prolongada em voluntÃrios sadios. Tratou-se de um estudo clÃnico, aberto, randomizado, cruzado, quatro perÃodos, duas sequÃncias, nos quais voluntÃrios sadios de ambos os sexos receberam 01 cÃpsula de venlafaxina 75mg de liberaÃÃo prolongada da formulaÃÃo teste e outra da formulaÃÃo referÃncia em cada perÃodo distinto em jejum ou alimentado, com um intervalo de sete dias. Foram coletadas 24 amostras de sangue em horÃrios previamente determinados. A concentraÃÃo da venlafaxina foi determinada utilizando o mÃtodo HPLC-MS/MS. A ausÃncia de efeito dos alimentos sobre a biodisponibilidade da venlafaxina foi indicada quando o intervalo de confianÃa de 90% para a razÃo geomÃtrica entre os estado em jejum e alimentado, esteve contido nos limites de equivalÃncia de 80-125% para o ASC0-inf, ASC0-t e Cmax quando comparado com a administraÃÃo do fÃrmaco no estado em jejum. Os eventos adversos foram monitorados durante todo o estudo. Trinta e trÃs voluntÃrios foram incluÃdos, 51,5% eram do sexo masculino (17 homens) e 48,5% do sexo feminino (16 mulheres). A idade mÃdia encontrada foi de 28,2 anos  8,6 anos, peso mÃdio de 66 kg  11,1 kg, altura mÃdia de 1,60 metros  0,1 m e Ãndice de massa corporal mÃdio (IMC) de 24,4 kg/m2  3,0 kg/m2. Os eventos adversos mais encontrados foram: cefaleia, representando 32,4%, sonolÃncia com 16,2% dos casos e nÃuseas, que representou 14,7%, dos episÃdios, nÃo havendo ocorrÃncia mais frequente em algum grupo (referÃncia ou teste) ou em estado alimentado ou jejum. Em relaÃÃo à farmacocinÃtica, nÃo foi encontrada diferenÃa estatisticamente significante na ASC0-tÃltimo e na ASC0-inf nos estados jejum versus alimentado nos grupos do medicamento referÃncia e teste; o Tmax foi menor e Cmax maior em ambos os grupos alimentados, o T1/2 foi menor no estado alimentado no medicamento teste. Em todos os parÃmetros exigidos para avaliaÃÃo do efeito dos alimentos na biodisponibilidade da medicaÃÃo referÃncia e teste estava contido no intervalo de confianÃa de 80-125%. Em relaÃÃo à bioequivalÃncia dos medicamentos, as formulaÃÃes referÃncia e teste no estado alimentado e em jejum tambÃm estavam dentro deste intervalo. Apesar de modificar alguns parÃmetros farmacocinÃticos, a alimentaÃÃo nÃo influenciou a biodisponibilidade da venlafaxina referÃncia e teste. As formulaÃÃes estudadas, cÃpsulas de liberaÃÃo prolongada de venlafaxina (produto teste e produto referÃncia) apresentaram biodisponibilidades semelhantes, quando administradas em dose Ãnica de 75 mg, por via oral a voluntÃrios sadios de ambos os sexos, em jejum e alimentados, sendo entÃo consideradas bioequivalentes para a velocidade e extensÃo de absorÃÃo. / The success of a therapeutic treatment depends upon the bioavailability of the drug, which can be influenced by food intake. This study aimed to evaluate the influence of food in the bioavailability of two formulations of venlafaxine administered at extended-release capsules in healthy volunteers. This open, randomized, crossover clinical trial was consisted of four periods, two sequences, in which healthy adult volunteers received 01 extended-release capsule of venlafaxina 75mg of test formulation and another of reference formulation in each distinct period under fasting or fed conditions, with an interval of seven days. 24 Blood samples were collected at predetermined times. Venlafaxine concentrations were determined through a HPLC-MS/MS method. The food did not influence the venlafaxine bioavailability when the 90 percent of confidence interval for the geometric ratio between fed and fasted treatment was contained in the equivalence limits of 80-125% for AUC0-inf, AUC0-t and Cmax when compared to administration of the drug in fasting condition. Adverse events were monitored during the study. Thirty-three subjects were included, 51.5% were male (17 men) and were 48.5% female (16 women). The mean age was 28.2 years  8.6 years, mean weight was 66 kg  11.1 kg, mean height was 160 cm  0.1 cm and the mean body mass index (BMI) was 24.4 kg/m2  3.0 kg/m2.. The most frequent adverse events were: headache representing 32.4%, drowsiness with 16.2% and nausea with 14.7% of all events. There was no significant difference in the frequency of occurrence in the groups (reference and test) related to the fasting or fed state. Regarding the pharmacokinetic parameters, in the statistical comparison, no difference was found in the AUC0-t and the AUC0-inf in the fasted versus fed conditions in the reference and test formulation groups. The Tmax was lower and the Cmax higher in both fed groups and the T1/2 was lower in the fed state in the test formulation. The confidence interval for all parameters required to evaluate the effect of food on the bioavailability of the reference and test formulations were within the range of 80-125%. Regarding the bioequivalence of drugs, both formulations in fed and fasted state were within the established range (80-125%). Although the food did change some pharmacokinetic parameters, feeding did not influence the bioavailability of venlafaxine in both reference and test formulations. The studied capsules of venlafaxine extended-release (test and reference products) showed similar bioavailability when administered a single oral dose of 75mg to healthy adult volunteers, fasting and fed and, thus, were considered bioequivalent to the rate and extent of absorption.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A equivalÃncia farmacÃutica entre dois medicamentos relaciona-se à comprovaÃÃo de que ambos contÃm o mesmo fÃrmaco na mesma dosagem e forma farmacÃutica, o que pode ser avaliado por meio de testes in vitro. No Brasil, os medicamentos alopÃticos sÃo divididos em trÃs categorias quanto ao registro junto à AgÃncia Nacional de VigilÃncia SanitÃria: medicamentos novos, medicamentos similares e medicamentos genÃricos. A legislaÃÃo atual dispÃe que para o registro de novos medicamentos genÃricos e similares à necessÃria a comprovaÃÃo da equivalÃncia farmacÃutica e a bioequivalÃncia em relaÃÃo ao medicamento de referÃncia. Produtos registrados antes de 2003 tÃm um perÃodo de adaptaÃÃo garantido, de modo que os resultados dos testes de equivalÃncia farmacÃutica e perfil de dissoluÃÃo sejam incluÃdos ao seu registro atà 2014. O Programa FarmÃcia Popular do Brasil à uma nova polÃtica de AssistÃncia FarmacÃutica, dentro do Sistema Ãnico de SaÃde que tem como objetivo facilitar o acesso da populaÃÃo aos medicamentos considerados bÃsicos e essenciais, diminuindo assim, o impacto dos preÃos dos medicamentos no orÃamento familiar. O objeivo deste trabalho foi avaliar a EquivalÃncia FarmacÃutica de comprimidos de Captopril 25 mg e Cloridrato de Propranolol 40 mg comercializados no Programa FarmÃcia Popular do Brasil, comparando-o com medicamentos de ReferÃncia e GenÃrico, visando discutir a importÃncia da qualidade dos medicamentos para a saÃde pÃblica. Realizaram-se testes fÃsicos e fÃsico-quÃmicos como: identificaÃÃo, determinaÃÃo de peso, desintegraÃÃo, dureza, friabilidade, teor, uniformidade de conteÃdo, pureza e perfil de dissoluÃÃo, segundo a FarmacopÃia Brasileira, 4a ediÃÃo. Os resultados indicaram uma baixa dureza nos comprimidos de cloridrato de propranolol da FarmÃcia Popular. Os perfis de dissoluÃÃo, analisados por ANOVA e teste de Tukey demonstraram diferenÃas significativas (p<0,001) entre os perfis de dissoluÃÃo da FarmÃcia popular em relaÃÃo ao GenÃrico e ReferÃncia nos tempos avaliados dos dois fÃrmacos em estudo. Compararam-se os perfis de dissoluÃÃo dos comprimidos da FarmÃcia Popular com os medicamentos ReferÃncia e GenÃrico atravÃs da EficiÃncia de DissoluÃÃo (ED%). A extensÃo do fÃrmaco dissolvido do medicamento FarmÃcia Popular foi significativamente menor (P < 0,001) do que o ReferÃncia para Captopril e Propranolol. O Captopril da FarmÃcia Popular, apesar de ter cumprido as exigÃncias da legislaÃÃo, foi reprovado no ensaio de ED%. Portanto, os comprimidos de Cloridrato de Propranolol e Captopril da FarmÃcia Popular nÃo foram considerados equivalentes farmacÃuticos em relaÃÃo aos medicamentos ReferÃncia e GenÃrico. / The pharmaceutical equivalence between two medicines is based on the confirmation that both contain the same active drug on the same dosage and dosage form, wich is assessed by in vitro tests. In Brazil, the National Health Surveillance Agency defines that allopathic medicines can be registered in three categories: innovator, generic and similar drugs. The actual legislation determines that to register new generic and similar medicines it is necessary to prove its pharmaceutical equivalence and bioequivalence with a reference drug. Products registered before 2003 have until 2014 to present these equivalence results. The Popular Pharmacy Program in Brazil is a new strategy of pharmaceutical assistance of the Health Sistem with the purpose to facilitate the populationâs access to medicines considered basic and essential, lowering the price impact of these medicines in the family budgets. The objective of this study was to assess the pharmaceutical equivalence of captopril 25 mg and propranolol hydrochloride 40 mg tablets sold in the Popular Pharmacy Program in Brazil, comparing them to a reference and generic drug, debating the importance of the quality of drugs for the public health. Physical and physicochemical tests such as identification, weight variation, disintegration, hardness, friability, purity, dosage, content uniformity, and dissolution profile, were performed according to the Brazillian Pharmacopeia 4th edition. The results showed a low hardness of propranolol hydrochloride tablets originated from the Popular Pharmacy Program. The dissolution profiles analised by analysis of variance (ANOVA) and Tukey test demonstrated significant differences between the dissolution profiles of both drugs originated from the Popular Pharmacy Program and their respective reference and generic drugs (p<0,001). The dissolution profiles were compared by the Dissolution Efficiency method. The extention of the active drug dissolved from the Popular Pharmacy medicine was significantly lower than the dissolution from the reference and generic drugs (P < 0,001) for both captopril and propranolol hydrochloride. Even though captopril would fulfill the requirements of the National Health Surveillance Agency to be considered equivalent, it was not approved on the dissolution efficiency test. Therefore, the assessed tablets originated from the Popular Pharmacy Program in Brazil were not considered pharmaceutical equivalents when compared to their respective reference and generic drugs.

Os enfermeiros têm a responsabilidade ética, legal e profissional de promover uma assistência segura na administração de medicamentos. A aprendizagem da administração de medicamentos está centrada no conhecimento que os enfermeiros constroem em sua formação acadêmica e na vivência profissional. O objetivo deste trabalho foi compreender o significado da administração de medicamentos, pelo estudante de enfermagem nas suas primeiras experiências. Dada a natureza do problema, esta investigação utilizou uma abordagem qualitativa, tendo como referencial metodológico a Teoria Fundamentada nos Dados, à luz do Interacionismo Simbólico. Como estratégias para a coleta de dados foi utilizada a observação não-participante e entrevistas semi-estruturadas, tendo como sujeitos 13 estudantes de uma instituição pública de ensino superior, localizada no interior do Estado de São Paulo. Os dados foram coletados, organizados e analisados por meio da estratégia da análise comparativa constante. Os resultados revelaram que os estudantes de enfermagem, ao vivenciarem o processo da administração de medicamentos, experienciaram insegurança ao administrar medicamentos; evidenciando as categorias: não valorizando a execução de determinados procedimentos básicos e emergindo sentimentos de dúvida para \"ser Enfermeiro\" no contexto desta ação. Como condições causais do fenômeno despontam a vivência de situações de erros e a percepção de conhecimentos teórico-práticos insuficientes; e como estratégia de ação a importância do laboratório e do campo de prática para o aprendizado. As condições intervenientes que influenciaram a realização dessa ação foram: tendo apoio dos colegas, família e professor e tendo dificuldades no relacionamento com o cliente. Como conseqüências as categorias: despertando para a responsabilidade da \"ação\" de administrar medicamentos e despertando para a profissão: sentindo-se enfermeiro ao administrar medicamentos. Enfim, os estudantes de enfermagem participantes do estudo atribuíram o significado da administração de medicamento como uma atividade de ilimitado valor e responsabilidade, conduzindo-os a um despertar para a futura profissão. / Nurses have the ethical, legal and professional responsibility to promote safe care in medication administration. Learning about medication administration is centered on the knowledge that nurses develop during their academic education and professional experience. This work aimed at understanding the meaning of medication administration to nursing students during their first experiences. Due to the nature of the problem addressed, a qualitative approach was used according to the Grounded Theory, in the light of Symbolic Interactionism. Non-participant observation and semi-structured interviews were used as strategies for data collection from 13 subjects who were students at a public college in São Paulo state. Data were collected, organized and analyzed through the strategy of constant comparative analysis. The results showed that, during the process of medication administration, the nursing students experienced insecurity according to the following categories: not valuing the execution of basic procedures and with feelings of doubt \"about being a nurse\" emerging in the context of this action. The causes for the phenomenon were: experiencing situations of error and the perception that theoretical and practical knowledge was insufficient. As action strategies, the following must be cited: the importance of laboratory and practical activities for learning; as interventional conditions that would influence the performance of this action: having support from colleagues, relatives, teachers and having difficulties in the relationship with the client, and as consequences: awakening to the responsibility of the \"action\" of administering medication and awakening to the profession: feeling as a nurse when administering medication. Finally, the nursing students participating in the study attributed the meaning of medication administration as an activity of unlimited value and responsibility which leads them to the awakening to a future profession.

Os efeitos protetores da imunidade humoral são medidas por uma família de glicoproteínas chamadas anticorpos ou imunoglobulinas. As preparações de imunoglobulina G (IgG) utilizadas em nosso país são importantes. No Brasil, a primeira preparação de IgG foi obtida na Fundação Pró-Sangue Hemocentro de São Paulo em 1993. O presente estudo avaliou preparações de IgG obtidas de misturas de plasma humano de variadas procedências, inclusive a preparação obtida no Brasil. Foram avaliados os seguintes parâmetros: concentração protéica, distribuição das subclasses da IgG, atividade de anticorpos específicos e segurança quanto a agentes patogênicos transmissíveis pelo sangue. Em algumas preparações, a concentração protéica de IgG e a distribuição das suas subclasses estavam fora das especificações. As preparações apresentaram atividade de anticorpos específicos contra os vírus das hepatites A e B, do herpes simples, da rubéola, citomegalovírus; contra a bactéria Streptococcus pyogenes &#946;-hemolítico do grupo A e contra o parasita Toxoplasma gondii. A qualidade de matéria-prima utilizada em algumas das preparações de IgG não foi adequada em função de reações positivas para anticorpos contra alguns agentes infecciosos, tais como HTLV I/II, HAV, HBV, HCV e Treponema pallidum. Esse estudo também mostrou a necessidade de se implantar urgente um programa abrangente para avalição das preparações de IgG a serem consumidas pela população brasileira. / A family of glicoproteins, which are called antibodies or immunoglobulins (IgG), mediates the protective effects of humoral immunity. In Brazil, the IgG for intravenous use are imported from other countries. The first Brazilian immunoglobulin G for therapheutic use was obtained from human plasma at the Fundação Pró-Sangue Hemocentro de São Paulo. The present study was carried out to evaluate different preparations of IgG, human plasmad-derived, include the preparation from Brazil. The protein concentration, IgG subclass distribution, specific antibody activities and safety regarding the main blood transmitted infectious diseases were analyzed. In some preparations, IgG protein concentration and subclass distribution were different from their specifications. Some preparations showed specific antibody activity against the following antigens: A and B hepatitis virus, rubella, herpes simplex virus, citomegalovirus, measles virus, Streptococcus pyogenes &#946;-hemolytic group A and Toxoplasma gondii. The presence of antibodies against antigens such as HTLV I/II, HAV, HBV, HCV and Treponema pallidum has compromissed the quality guaranty of the material-source (plasma) used in some preparations. This study has also showed that a complete and effective program for the quality evaluation of IgG preparations used in Brazil is needed and should be urgently established

The topical application of many substances, including drugs, enzymes, moisturizers and fragrances, contributes largely to the cosmetic and pharmaceutical industries. These components are often volatile in nature and dissipate in a matter of hours. When considering the different types of slow release systems, an overwhelming variety of these systems is available. Each one of the systems is unique in a way, and is designed to perform a particular function, whether it facilitates the controlled release of an active into the body via the skin surface (transdermal delivery) or whether it reduces the rate of loss of an active from the skin surface to the surrounding environment. For the purpose of this study, a previously existing fixative formulation which is believed to reduce the rate of loss of an active component to the environment, through film formation on the skin surface, was investigated. Alternative ingredients or components were incorporated together with the original fixative formulation ingredients into an experimental design which investigates the effect of each group of the components present. 18 formulations with various concentrations of the components within the groups and specified upper and lower limits for each component were formulated. The fixative properties of the formulations were analysed through the incorporation of a fixed amount of a simple fragrance molecule, 4- methoxybenzaldehyde, into each formulation and evaporation studies were conducted in an environmental room at 28±1° C over a period of 5 hours followed by gas chromatography analysis and finally data analyses using statistical methods. The most efficient fixative formulation was established using regression analysis. The fragrance compound in this formulation was found to evaporate at a rate of 0.47 g/L per hour. The least efficient fixative formulation lead to the loss of 0.78 g/L of the fragrance component per hour. From the calculated fragrance concentrations, the rate constant for each individual fixative formulation could be calculated and response surface 8 modelling by backward regression was used in order to determine how each component contributes to the rate of loss of the fragrance compound. Since the sum of the original ingredient and its alternative was constant, each of the original ingredients was coupled directly to its alternative and no conclusion could be made about the contribution of individual components. By increasing the concentration of Hydroxypropylcellulose (HPC) 100K and its alternative HPC 140K, while keeping the effects of the other components constant, a decrease in the rate of fragrance loss was observed. The same conclusion could be made when increasing the concentrations of PEG-12 Dimethicone and its alternative cetyl dimethicone (decreases the evaporation rate). An interaction took place between HPC 100K and PEG-12 dimethicone and their alternatives. The negative effect was, however, not as strong as the combined positive effect on the rate of fragrance loss of the individual components HPC and PEG-12 dimethicone. Evidence suggested that the removal of the components polyvinylpyrrolidone and its alternative, polyurethane-32 (Baycusan® C1003), would improve the effectiveness of the fixative formulation in terms of its slow release properties. A confirmation experiment established that the exclusion of these components from the fixative formulation does improve the “slow release” properties thereof. A larger, more intricate design is required to investigate the effect of each one of the individual components and where the sum of the components (original and its alternative) is not constant.

A review of the literature on blood stream infections caused by contaminated intravenous infusates which are prepared in clinical care settings found that this common nursing procedure poses at times a significant and life-threatening risk to patients. The guidance and regulations surrounding the preparation of intravenous drugs in clinical care settings suggests that this procedure is extremely complex and poses many different potential hazards to patients. This thesis set out to determine how the infection risks are being addressed in practice by asking the questions: ‘What is the system of intravenous drug preparation in clinical care settings in NHS Scotland?’ and, ‘How does it work in practice?’ Several data sources were utilised: six locations, in specialities where the literature identified significant outbreaks had occurred, were examined for potential contamination risk. Observations (78) of infusate preparations were undertaken and, where available, written procedures were compared with observed practices. Finally, analyses were made of 71 questionnaires, completed by the nurses who prepare intravenous drugs, regarding their opinions of the procedures’ safety and when they perform redundancy checks. The conclusion of this study is that the system of preparing intravenous drugs in clinical care settings by nurses is, as a consequence of potential infusate contamination, error-prone and unreliable. The reasons for this conclusion are now detailed. o Due to a lack of mandatory environmental standards, and the provision of poor environments, there is a risk of infusate contamination from environmental sources and consequently, a risk to patients of infusate-related blood stream infections (IR-BSI). o Some in use equipment poses contamination risks to patients’ infusates. Equipment that could reduce the contamination risk is not always available and in some instances such safety-enhancing equipment has been removed. o There are no complete written procedures which mirror what is done in practice. At present, from a human-factors perspective, it is not easy for the nurse to do the right thing, or to be sure exactly what is the right thing to do. o The procedure, in practice, has the required elements of an aseptic procedure, but the execution of the procedure is more often not performed aseptically. o The procedure of intravenous drug preparation as observed is mainly an interrupted aseptic procedure and as such the recommencement of the aseptic procedure requires repeated hand hygiene. o The nurses’ opinions of safety vary, as did their assessment of the infection risk to their patients, but it is clear that intravenous drug preparation is not a much-loved nursing procedure and some nurses find it very stressful. o There is no asepsis quality control built into the system. Aseptic steps are the least likely to be performed as a redundancy check compared to the mandatory checks of ‘right patient, right drug and right dose’. o The information available to the nurses, from the drug companies, from the makers of equipment and from national agencies does not identify with sufficient clarity the infection risks, or detail how to negate them. Suggestions for improvement to the six procedures and environments are clear once the procedure steps are colour-coded as either aseptic or non-aseptic; validity testing of these improvements is however, still needed. The systems’ vulnerabilities observed in this research appear to stem from a chain of external influences including an underestimation of the problem size and the actions needed to prevent it in evidence-based guidelines and mandatory guidance. This leads to poor recognition of the risk of IR-BSI in clinical practice. The problem of infusate contamination causing IR-BSIs is further compounded by the fact that it is not caused by a single organism and does not always present as a disease in real time, that is, over the lifetime of the infusion. As a consequence, this presents surveillance difficulties in terms of definitions, data collection and analysis. Finally, although the diagnosis of a blood stream infection for an individual patient remains relatively easy, it is not easy to recognise a contaminated infusate as the origin of the problem. All these challenges make both the recognition of the problem and agreement on prevention strategies, extremely challenging. In summary, the main conclusion of this thesis is that the preparation of infusates in clinical care settings, which occurs approximately 3,000,000 times a year in NHSScotland, is from an aseptic perspective, error-prone and unreliable. Recommendations to optimise patient safety include, changing the procedure locally and, with the utmost urgency, the production of minimum environmental standards. The results of this study are relevant to all hospitals in Scotland and throughout the United Kingdom where the current regulations apply and similar procedures are performed.

The weight loss industry has come under fire from the Federal Trade Commission (FTC) in recent years due to consumer claims that many firms, marketing weight loss products, are using advertisements in an attempt to deceive consumers. Illegitimate weight loss claims have created so much concern that a White Paper call-to-action to investigate misleading weight loss advertisements has been filed. Despite recent interest, little attention has been garnered concerning the understanding of why consumers respond to potentially misleading weight loss claims. Intuitively, an understanding of why consumers fall prey to weight loss claims may aid academics, practitioners, and policy makers as they make important decisions relative to the weight loss industry and its practices. This study fills that void by applying a theory of visceral influences (TVI) to the context of weight loss advertising. Loewenstein's TVI was developed to aid in explaining why consumers make decisions contrary to their long-term self-interest. Visceral influences are drive states that have a direct hedonic impact, have an effect on the relative desirability of various goods and activities, and consequently, have a strong influence over the decisions consumers make. Common visceral cues (cues associated with any reward linked to a visceral factor) include proximity of reward, vividness of reward, and visual priming. To adequately test TVI in the context of weight loss advertising, a two step approach was used. First, advertiser intent was assessed through content analysis of weight loss advertisements. Second, composite advertisements were created from the content analysis to assess subject response to visceral cues common in weight loss advertising. MANOVA results show that the presence of visceral cues affected subjects' thoughts, buying impulse, affective reaction, intentions, and product evaluation. This research makes the following contributions. First, it addresses an area of public policy where there is a need for research to shape future legislation. Second, it provides an initial empirical examination of the effects of visceral cues on subjects' providing a foundation for further application and theory building. Third, it reveals that visceral cues effects are moderated by an individual's level of involvement with a reward.

Submitted by Haroudo Xavier Filho (haroudo.xavierfo@ufpe.br) on 2016-04-14T18:22:12Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação -Marciana S_ F_ Cordeiro _1_.certa.pdf: 3647564 bytes, checksum: f459470e06543d55f9f637a82005d075 (MD5) / Made available in DSpace on 2016-04-14T18:22:12Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação -Marciana S_ F_ Cordeiro _1_.certa.pdf: 3647564 bytes, checksum: f459470e06543d55f9f637a82005d075 (MD5) Previous issue date: 2015-02-25 / CNPq / O cloridrato de pilocarpina vem sendo utilizado no tratamento da xerostomia, entretanto sua atuação sistêmica promove reações adversas indesejáveis. Contudo, os atuais sistemas de liberação prolongada de fármacos, podem controlar variações de concentração plasmática e reduzir estes efeitos colaterais. Adicionalmente, a obtenção de comprimidos mucoadesivos associado a este sistema de liberação favorece a ação prolongada do fármaco na cavidade oral, trazendo benefícios importantes para o tratamento. Assim, este trabalho tem como objetivo o desenvolvimento de comprimidos mucoadesivos a base de cloridrato de pilocarpina para o tratamento da xerostomia, utilizando para este propósito a mistura física da goma do cajueiro/pilocarpina, quitosana/pilocarpina, mistura física de ambos os polímeros com pilocarpina e desenvolvimento de uma blenda polimérica por liofilização contendo goma de cajueiro e quitosana. Inicialmente a compatibilidade fármaco-polímero foi avaliada através da Calorimetria Exploratória Diferencial (DSC), Termogravimetria (TG), Espectroscopia de Infravermelho (IV) e Difração de Raios-X (DRX). Em seguida, foram obtidos comprimidos por compressão direta. Os comprimidos obtidos foram submetidos ao controle de qualidade, avaliação mucoadesiva e perfil de liberação. Na avaliação da mistura física (MF) dos polímeros/pilocarpina e da blenda/pilocarpina não foram encontrados sinais de incompatibilidades diante da avaliação pelas técnicas de DSC e TG. Dentre as formulações desenvolvidas, a blenda/pilocarpina demonstrou agregar propriedades mucoadesivas e retardo na liberação do fármaco, propriedades estas não encontradas nos polímeros individualmente e na mistura física/pilocarpina. A blenda/pilocarpina apresentou liberação de 53% do fármaco no tempo 180 min., tempo de mucoadesão de 510 min e incremento da força de mucoadesão. Esses resultados mostram o potencial do sistema polimérico para futuros desenvolvimentos na área farmacêutica. / The pilocarpine hydrochloride has been used in the treatment of xerostomia, however its systemic activity promotes undesirable side effects. However, the current prolonged release of drugs can control variations in plasma concentration and reduce these side effects. Additionally, to obtain tablets mucoadhesive associated with this delivery system favors prolonged drug action in oral cavity, which has important benefits for treatment. This work aims to develop mucoadhesive tablets pilocarpine hydrochloride base for the treatment of xerostomia, using for this purpose the physical mixture of cashew gum/pilocarpine, chitosan/pilocarpine, physical mixture of both polymers with pilocarpine and development of a polymer blend by lyophilization containing cashew gum and chitosan. Initially the drug-polymer compatibility was evaluated by Differential Scanning Calorimetry (DSC), thermogravimetry (TGA), Infrared Spectroscopy (IR) and X-ray Diffraction (XRD). Then, tablets were obtained by direct compression. The tablets were subjected to quality control, mucoadhesive evaluation and release profile. In assessing the physical mixture (MF) of the polymers / pilocarpine and blend / pilocarpine were not incompatible signals found on the evaluation by DSC and TG techniques. Among the developed formulations, the blend / pilocarpine shown add mucoadhesive properties and delayed drug release, these properties not found in polymers individually and physical / pilocarpine mixture. The blend / pilocarpine showed 53% release of the drug in time 180 min. Mucoadhesion time of 510 min, and increased strength mucoadhesion. These results show the potential of the polymer system for future developments in the pharmaceutical field.

Recent pharmaceutical developments have investigated using supramolecular nanoparticles in order to increase the bioavailability and solubility of drugs delivered in various methods. Modification of the carbohydrate cyclodextrin increases the ability to encapsulate hydrophobic pharmaceutical molecules by forming a carrier with a hydrophobic core and hydrophilic exterior. Guest molecules are commonly added to these inclusion complexes in order to add stability and further increase targeting abilities of the carriers. One such guest molecule is adamantine combined with a poly(ethylene glycol) chain. Vesicles are formed by hydrating a thin film of amphiphilic cyclodextrin and guest molecules in buffer solution that mimics physiological conditions. The solution is subject to freeze-thaw cycles and extrusion, and the complexes are separated out via size exclusion chromatography. Dynamic Light Scattering instrumentation is used to observe the particle size distribution. Cargo release can be observed in fluorescent dye-loaded vesicles by addition of a membrane-cleaving agent under a fluorimeter instrument. Future work involving this drug delivery technology includes synthesizing a chemically sensitive guest that will cleave in the presence of an intra-cellular anti-oxidant, and finally observing the uptake of these vesicles into live cells and testing the delivery of cargo in vitro under physiological conditions.

Charles University Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical Technology Author: Jakub Tisoň Title of thesis: Evaluation of rheological properties of nasal sprays Supervisor: PharmDr. Eva Šnejdrová, Ph.D. The aim of the submitted diploma thesis was to develop a comprehensive methodology for testing the rheological and especially thixotropic properties of nasal suspensions. Characterize the original preparation Avamys® and samples of a generic preparation at various stages of the formulation by selected tests. Within the theoretical part of the work, the nasal application of drugs, nasal preparations were discussed, the basics of rheometry were summarized and the principle of relevant rheological tests was described. Flow curves were measured on a Kinexus rotary rheometer using plate-to-plate geometry and analyzed by power law. The yield stress of nasal suspensions was determined. The thixotropic properties were evaluated by the area of the hysteresis loop, and especially by the three-step thixotropy test. The conformity of selected rheological characteristics of the tested samples with the original preparation was evaluated. Key words: nasal sprays, viscosity, yield stress, thixotropy.