Efavirenz dissolution enhancement V - A combined top down/bottom up approach on nanocrystals formulation

Abstract Efavirenz is one of the most commonly used drugs in HIV therapy. However the low water solubility tends to result in low bioavailability. Drug nanocrystals, should enhance the dissolution and consequently bioavailability. The aim of the present study was to obtain EFV nanocrystals prepared by an antisolvent technique and to further observe possible effect, on the resulting material, due to altering crystallization parameters. A solution containing EFV and a suitable solvent was added to an aqueous solution of particle stabilizers, under high shear agitation. Experimental conditions such as solvent/antisolvent ratio; drug load; solvent supersaturation; change of stabilizer; addition of milling step and solvents of different polarities were evaluated. Suspensions were characterized by particle size and zeta potential. After freeze- dried and the resulting powder was characterized by PXRD, infrared spectroscopy and SEM. Also dissolution profiles were obtained. Many alterations were not effective for enhancing EFV dissolution; some changes did not even produced nanosuspensions while other generated a different solid phase from the polymorph of raw material. Nevertheless reducing EFV load produced enhancement on dissolution profile. The most important modification was adding a milling step after precipitation. The resulting suspension was more uniform and the powder presented grater enhancement of dissolution efficacy.

Use of biorelevant dissolution media in dissolution tests as a predictive method of oral bioavailability

Abstract Dissolution is a key step in the uptake of oral drugs. In order to compare the behaviour of the dissolution of two formulations, the dissolution profile test was used. This assay must be discriminative and should mimic in vivo conditions. Many dissolution media described in pharmacopoeias are not predictive of bioavailability. Due to this, biorelevant media are used as an alternative to solve this problem. The objective of this work is to evaluate the relevance of biorelevant dissolution media to predict in vivo drug dissolution. For this, a bibliographic search was carried out in scientific databases. The search was first performed for articles verifying the physicochemical properties of human gastrointestinal fluids. Subsequently, a comparison was made between the properties of gastrointestinal fluids and those of biorelevant and pharmacopoeial media. Finally, the results of bioequivalence studies and dissolution profile tests in biorelevant media described in the literature were compared. The results revealed that there are a few publications that have analysed some physicochemical properties of gastrointestinal fluids. In addition, high variability was observed for some properties. Regarding the comparison of these properties with pharmacopoeial media and biorelevant media, the analysis showed that the biorelevant media are more similar to gastrointestinal fluids than the pharmacopoeial media. Finally, the in vitro dissolution profile results were similar to the results obtained in vivo. Thus, biorelevant media may be useful for analysing dissolution profiles.

Saúde Coletiva e uma escolha de Sofia: defender a privacidade no ciberespaço / Collective Health and a Sophie's Choice: to defend privacy in cyberspace

Resumo A atualidade vivencia complexas ameaças à privacidade na saúde (PS), no contexto de crescente virtualização dos corpos e de biografias expostas nas redes sociais. O artigo objetiva conhecer as abordagens sobre a PS na produção científica brasileira à luz da Saúde Coletiva (SC). Realiza estudo exploratório, analítico-descritivo, com revisão de artigos de periódicos brasileiros de excelência da SC de 2000 a 2017. Foram selecionados artigos que adotam a PS como objeto. Evidenciou-se que, em comum, ancoram-se na perspectiva de que o 'medo do profissional à punição' é a fronteira para inibir ações de violação da PS. Porém, nem o arcabouço jurídico-normativo, nem o apparatus tecnológico de segurança, tem sido suficiente. No SUS, ameaças se intensificam em iniciativas do Cartão SUS, PEP, Centrais de Regulação e Telessaúde. Os resultados corroboram com a hipótese de que existe uma lacuna na produção sobre a temática em periódicos de excelência da SC. Discute-se: omissão das instituições; adoção de TCLE para uso de dados individuais; opacidade sobre o faturamento dos gastos públicos no apparatus tecnológico de segurança. O respeito à PS precisa tornar-se fruto de um pacto político-ético, onde todos passem a agir eticamente na defesa da privacidade por opção e não por coação e medo de penalidades.

Abstract The world is currently experiencing complex threats to privacy in health (PH) in the context of the growing virtualization of bodies and biographies exposed in social networks. This paper aims to identify the approaches to PH in Brazilian scientific production in the light of Collective Health (CH). This is an exploratory, analytical-descriptive study reviewingpapers from Brazilian Collective Health journals of excellence from 2000 to 2017. Papers employing PH as their object were selected for further analysis. We found that papers are commonly anchored in the perspective that the "professional's fear of punishment" is the borderline inhibiting PH violation actions. However, neither the legal-normative framework nor the technological security apparatus sufficed. In the Unified Health System (SUS), threats escalate in initiatives of the SUS Card, PEP, Regulatory Centers and Telehealth. The results corroborate a hypothetic gap in the production of the subject in Collective Health journals of excellence. The discussion is about institutional omission; adoption of the ICF for the use of individual data; opacity on the revenue of public expenditure in the technological security apparatus. Respect for PH must bethe result of a political-ethical agreement, in which all start to act ethically in defense of privacy by choice and not coercion and fear of penalties.

Prednisone raw material characterization and formulation development

ABSTRACT Solid dosage forms for oral use, particularly tablets, are the most highly used dosage forms in therapy because they are easily administered, have high productivity and relatively low cost and provide a more stable drug to form a semi-solid net. Numerous parameters influence the quality of the final dosage form. In this study, the dissolution profile of 20-mg prednisone tablets bioequivalent to the reference product and three test formulations were evaluated using stability testing. During the study, prednisone tablets and the active pharmaceutical ingredient (API) prednisone from two different manufacturers were characterized with respect to their physical and physicochemical properties. The results showed that the dissolution profiles of the test batches and the reference product did not retain pharmaceutical equivalence throughout all the stability study. Notably, both samples of API prednisone were of the same crystal form, and any phase transition that occurred during the study could not be attributed to dissolution variation during stability.

The Entomological Collection of Ricardo von Diringshofen (1900–1986) and its incorporation to the Museu de Zoologia da Universidade de São Paulo

ABSTRACT Ricardo von Diringshofen (1900–1986) was a Natural History enthusiast who collected an incredible variety of objects, mostly insects, which amount to over 2 million specimens. We present here a brief biography of Ricardo von Diringshofen, including the history of his insect collection and the processes of purchase and incorporation of his collection by the Museu de Zoologia da Universidade de São Paulo.

Preparação e caracterização no estado sólido de polimorfos do mebendazol / Preparation and solid state characterization of mebendazole polymorphs

O polimorfismo é um fenômeno de grande importância no desenvolvimento de um medicamento. Os polimorfos de um fármaco podem apresentar propriedades físico-químicas diferentes. A pesquisa de polimorfos envolve a realização de experimentos e a caracterização por diferentes técnicas. Neste trabalho, o mebendazol foi escolhido para o estudo de polimorfos. Assim, experimentos de cristalização foram realizados. As amostras foram caracterizadas por diferentes técnicas. Três polimorfos foram obtidos. Os resultados evidenciaram características morfológicas e físico-químicas que permitiram diferenciar as formas cristalinas do mebendazol. Por fim, dez medicamentos comerciais foram avaliados por difração de raios X. Verificou-se a presença, em alguns casos, da forma A, ineficaz, do mebendazol. Este trabalho demonstra que variando-se as condições experimentais é possível obter polimorfos diferentes do mebendazol, inclusive a forma A, não desejada nas formulações. Os métodos analíticos utilizados possibilitam a diferenciação dos polimorfos do mebendazol.

Habilidades de leitura em crianças com diagnóstico de hiperlexia: relato de caso / Reading skills in children diagnosed with hyperlexia: case reports

Hiperlexia caracteriza-se pela aquisição espontânea e precoce da habilidade de leitura, manifestada antes dos cinco anos, na ausência de instrução formal. Déficit da linguagem expressiva e receptiva, excelente memória, atraso nas habilidades linguísticas, ecolalia, perseverações e dificuldade para compreensão do contexto verbal são sintomas comuns em indivíduos hiperléxicos com transtorno global do desenvolvimento, incluindo a Síndrome de Asperger. O objetivo deste estudo foi descrever as habilidades de leitura de indivíduos que apresentam hiperlexia. Participaram seis meninos, com histórico de hiperlexia percebida pelos familiares antes dos 36 meses de vida, de idade cronológica variando de quatro anos e quatro meses a cinco anos e dois meses. Foram aplicados os seguintes procedimentos de avaliação: entrevista com os responsáveis, observação do comportamento comunicativo, Teste de Vocabulário por Imagens Peabody (TVIP), reconhecimento de letras do alfabeto e números, Teste de Desempenho Escolar, leitura de texto e compreensão de leitura. Os participantes apresentaram desempenhos diferentes no TVIP, demonstraram reconhecimento de letras e números e de palavras isoladas. Entretanto, foram verificadas diferenças no desempenho deles. Houve dificuldade em responder ao subteste de escrita; a maioria não compreendeu o texto lido e todos demonstraram reconhecer letras e números, sendo alguns deles com habilidade de leitura de palavras e texto. Porém, apresentaram alterações em outras áreas do desenvolvimento da linguagem, como vocabulário receptivo, comportamento comunicativo e compreensão do material lido, somados aos comportamentos alterados de adaptação social, interativos e restritivos.

Hyperlexia is characterized by spontaneous and early acquisition of reading skills, manifested before the age of five, without any formal education. Expressive and receptive language deficit, excellent memory, delayed language skills, echolalia, perseverations, and difficulty to understand verbal contexts, are common symptoms in individuals with hyperlexia and global developmental disorders, including Asperger's syndrome. The aim of this study was to describe the reading skills of individuals with hyperlexia. The participants were six boys with a history of hyperlexia, perceived by relatives before 36 months of life, chronologically aged between four years and four months to five years and two months. The following evaluation procedures were applied: interview with the parents or responsible guardians, communicative behavior observation, Peabody Picture Vocabulary Test (PPVT), recognition of alphabet letters and numbers, School Performance Test, text reading, and reading comprehension. The participants showed different performances in the PPVT, and recognized letters, numbers and isolated words. There was difficulty in answering the writing subtest; the majority did not understand the text that they read and all of them demonstrated recognition of letters and numbers. Some participants were able to read words and texts. However, all participants presented alterations in other areas of language development, such as receptive vocabulary, communicative behavior and understanding of the material read, in addition to altered behaviors of social adaptation, both interactive and restrictive.

Desempenho psicolinguístico e escolar de irmãos com mielomeningocele / Psycholinguistic and school performance of brothers with myelomeningocele

TEMA: mielomeningocele e consequências para o desenvolvimento de habilidades psicolinguísticas e escolares. PROCEDIMENTOS: o objetivo deste estudo foi descrever e refletir sobre o desempenho psicolinguístico e escolar de irmãos com mielomeningocele lombar baixa. Participaram do estudo um menino de 14 anos e 5 meses (P1) e sua irmã de 6 anos e 6 meses (P2). Os procedimentos constaram de entrevista com familiares, Observação do Comportamento Comunicativo (OCC), Teste de Vocabulário por Imagens Peabody - TVIP, Teste Illinóis de Habilidades Psicolinguísticas (ITPA), Perfil de Habilidades Fonológicas (PHF), Teste de Desempenho Escolar (TDE), e Reconhecimento de letras e números (RLN). A análise dos resultados foi descritiva respeitando os manuais dos instrumentos. RESULTADOS: a linguagem oral encontra-se sem alteração evidente. No ITPA e PHF, verificou-se que P1 e P2 apresentaram dificuldade nas habilidades de memória, closura auditiva, expressão verbal, combinação de sons e consciência fonológica. P1 ainda apresentou dificuldade na habilidade de recepção visual e P2 nas habilidades de associação auditiva e closura gramatical. Ambas as crianças apresentaram alteração nas atividades de aprendizagem. CONCLUSÃO: os participantes do estudo apresentaram comportamento comunicativo, habilidades de linguagem oral e vocabulário receptivo sem alterações evidentes. P1 e P2 apresentaram alterações nas habilidades psicolinguísticas bem como no desempenho de atividades envolvendo leitura, escrita e aritmética. As dificuldades apresentadas causam impacto importante nas atividades acadêmicas, demonstrando vulnerabilidade cerebral no sistema de suporte para atividade de aprendizagem.

BACKGROUND: meningomyelocele and consequences on the development of psycholinguistic and school abilities. PROCEDURES: the purpose of this study was to describe and reflect on the psycholinguistic and school performance of siblings with low lumbar myelomeningocele. The study included a boy, 14 years and 5 months (P1) and his sister, 6 years and 6 months (P2). The procedures consisted of an interview, Communicative Behavior Observation (CBO), Vocabulary Test Peabody Picture - PPVT, Illinois Test of Psycholinguistic Abilities (ITPA), Phonological Abilities Profile (PAP), School Performance Test (SPT), and recognition of letters and numbers (RLN). The analysis was descriptive and respecting the manuals of the instruments. RESULTS: the oral language has no obvious change. In ITPA and PAP, we found that P1 and P2 had difficulty in memory skills, closure listening, verbal, combination of sounds and phonological awareness. P1 still had difficulty in the ability of visual reception and P2 in the abilities of auditory association and closure grammar. Both children showed difficulties in the learning activities. CONCLUSION: the study subjects performed quite well in communicative skills, oral language and receptive vocabulary without obvious changes. P1 and P2 had changes in psycholinguistic skills and performance of activities involving reading, writing and arithmetic. Difficulties cause major impact on academic activities, demonstrating the vulnerability of the brain in the system supporting learning activity.

Síndrome do X Frágil com variante de Dandy-Walker: estudo clínico das manifestações comunicativas orais e escritas / Fragile X syndrome with Dandy-Walker variant: a clinical study of oral and written communicative manifestations

A síndrome do X Frágil é a causa mais frequente de deficiência intelectual hereditária. A variante de Dandy-Walker trata-se de uma constelação específica de achados neurorradiológicos. Este estudo relata achados da comunicação oral e escrita de um menino de 15 anos com diagnóstico clínico e molecular da síndrome do X-Frágil e achados de neuroimagem do encéfalo compatíveis com variante de Dandy-Walker. A avaliação fonoaudiológica foi realizada por meio da Observação do Comportamento Comunicativo, aplicação do ABFW - Teste de Linguagem Infantil - Fonologia, Perfil de Habilidades Fonológicas, Teste de Desempenho Escolar, Teste Illinois de Habilidades Psicolinguísticas, avaliação do sistema estomatognático e avaliação audiológica. Observou-se: alteração de linguagem oral quanto às habilidades fonológicas, semânticas, pragmáticas e morfossintáticas; déficits nas habilidades psicolinguísticas (recepção auditiva, expressão verbal, combinação de sons, memória sequencial auditiva e visual, closura auditiva, associação auditiva e visual); e alterações morfológicas e funcionais do sistema estomatognático. Na leitura verificou-se dificuldades na decodificação dos símbolos gráficos e na escrita havia omissões, aglutinações e representações múltiplas com o uso predominante de vogais e dificuldades na organização viso-espacial. Em matemática, apesar do reconhecimento numérico, não realizou operações aritméticas. Não foram observadas alterações na avaliação audiológica periférica. A constelação de sintomas comportamentais, cognitivos, linguísticos e perceptivos, previstos na síndrome do X-Frágil, somada às alterações estruturais do sistema nervoso central, pertencentes à variante de Dandy-Walker, trouxeram interferências marcantes no desenvolvimento das habilidades comunicativas, no aprendizado da leitura e escrita e na integração social do indivíduo.

The Fragile X syndrome is the most frequent cause of inherited intellectual disability. The Dandy-Walker variant is a specific constellation of neuroradiological findings. The present study reports oral and written communication findings in a 15-year-old boy with clinical and molecular diagnosis of Fragile X syndrome and neuroimaging findings consistent with Dandy-Walker variant. The speech-language pathology and audiology evaluation was carried out using the Communicative Behavior Observation, the Phonology assessment of the ABFW - Child Language Test, the Phonological Abilities Profile, the Test of School Performance, and the Illinois Test of Psycholinguistic Abilities. Stomatognathic system and hearing assessments were also performed. It was observed: phonological, semantic, pragmatic and morphosyntactic deficits in oral language; deficits in psycholinguistic abilities (auditory reception, verbal expression, combination of sounds, auditory and visual sequential memory, auditory closure, auditory and visual association); and morphological and functional alterations in the stomatognathic system. Difficulties in decoding the graphical symbols were observed in reading. In writing, the subject presented omissions, agglutinations and multiple representations with the predominant use of vowels, besides difficulties in visuo-spatial organization. In mathematics, in spite of the numeric recognition, the participant didn't accomplish arithmetic operations. No alterations were observed in the peripheral hearing evaluation. The constellation of behavioral, cognitive, linguistic and perceptual symptoms described for Fragile X syndrome, in addition to the structural central nervous alterations observed in the Dandy-Walker variant, caused outstanding interferences in the development of communicative abilities, in reading and writing learning, and in the individual's social integration.