Microemulsions as drug delivery systems for topical ocular administration

The conventional ophthalmic dosage forms are relatively simple: usually, water-soluble drugs are delivered in aqueous solution and water-insoluble drugs are prepared as suspensions or ointments. However, these delivery systems currently used present very low corneal bioavailability, systemic exposure because of nasolacrimal drainage and lack of efficiency in the posterior segment of ocular tissue. Recent research efforts have focused on the development of new ophthalmic drug delivery systems. As a result of these efforts, microemulsions are promising dosage forms for ocular use. These delivery systems are dispersions of water and oil that require surfactant and co-surfactant agents in order to stabilize the interfacial area. The microemulsions have a transparent appearance, thermodynamic stability and small droplet size of the dispersed fase (<1,0 mm), providing them with the capacity of being sterilized by filtration. Furthermore, these systems offer additional advantages that include: low viscosity, great ability as drug delivery vehicles, widened properties as absorption promoters and easiness of preparation, which do not require much energy and the use of special equipments. In this review, we present the technology and some preliminary studies of microemulsions in relation to ocular drug delivery systems.As formas farmacêuticas oftálmicas convencionais são relativamente simples: drogas solúveis em água são formuladas em solução aquosa e drogas pouco solúveis em suspensão ou pomada. Entretanto, essas formulações apresentam como inconvenientes baixa biodisponibilidade corneal, absorção sistêmica devida à drenagem nasolacrimal e reduzida eficácia no segmento posterior do olho. Assim, o desenvolvimento de novos sistemas de liberação de drogas de administração oftálmica tem sido um dos principais temas de pesquisa em tecnologia farmacêutica nos últimos anos. Entre as alternativas avaliadas, destacam-se principalmente as microemulsões. Estas formas farmacêuticas que são dispersões de água e óleo, estabilizadas por um emulsionante e por um co-emulsionante, transparentes, termodinamicamente estáveis, apresentam partículas de tamanho menor que 1,0 mm e, portanto, passíveis de serem esterilizadas por filtração. Além disso, as microemulsões apresentam baixa viscosidade, possuem grande capacidade para o transporte de drogas, demonstram comprovada propriedade promotora de absorção para as drogas veiculadas e são facilmente obtidas, sem a necessidade de utilização de equipamentos sofisticados e de componentes de custo proibitivo. O presente artigo objetiva revisão de literatura abordando o tema e os principais estudos relacionados com a utilização de microemulsões como sistemas de liberação de drogas oftálmicas.Universidade Federal de Minas Gerais Faculdade de FarmáciaUniversidade Federal de São Paulo (UNIFESP)Universidade Federal de Minas Gerais Hospital das Clínicas Serviço de UveítesUniversidade Federal de Minas GeraisUNIFESPSciEL

Development and validation of a High Performance Liquid Chromatographic method for determination of etoposide in biodegradable polymeric implants

A method using HPLC-UV was developed and validated for the determination of etoposide incorporated into polycaprolactone implants. The method was carried out in isocratic mode using a C18 column (250 x 4.6 mm; 5 µm), at 25 ºC, with acetonitrile and acetic acid 4% (70:30) as mobile phase, a flow rate of 2 mL/min, and UV detection at 285 nm. The method was linear (r² > 0.99) over the range of 5 to 65 µg/mL, precise (RSD < 5%), accurate (recovery of 98.7%), robust, selective regarding excipient of the sample, and had a quantitation limit equal to 1.76 µg/mL. The validated method can be successfully employed for routine quality control analyses

DEVELOPMENT AND VALIDATION OF A HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC METHOD DETERMINATION OF ZIDOVUDINE ENCAPSULATED IN PCL NANOPARTICLES

A reversed-phase high-performance liquid chromatographic (HPLC) method was developed and validated for the determination of encapsulation efficiency of zidovudine in nanoparticules. The method was carried out in isocratic mode using 0.040M sodium acetate: methanol: acetonitrile: glacial acetic acid (880:100:20:2) as mobile phase, a C8 column at 25ºC and UV detection at 240 nm. The method was linear (r2 ˃ 0.99) over the range of 25.0-150.0 μg/mL, precise (RSD ˂ 5%), accurate (recovery = 100.5%), robust and selective. The validated HPLC-UV method can be successfully applied to determine the rate of zidovudine in nanoparticules.A reversed-phase high-performance liquid chromatographic (HPLC) method was developed and validated for the determination of encapsulation efficiency of zidovudine in nanoparticules. The method was carried out in isocratic mode using 0.040M sodium acetate: methanol: acetonitrile: glacial acetic acid (880:100:20:2) as mobile phase, a C8 column at 25ºC and UV detection at 240 nm. The method was linear (r2 ˃ 0.99) over the range of 25.0-150.0 μg/mL, precise (RSD ˂ 5%), accurate (recovery = 100.5%), robust and selective. The validated HPLC-UV method can be successfully applied to determine the rate of zidovudine in nanoparticules

Oral myiasis in a patient with neurological deficit - Case report / Miíase oral em paciente com déficit neurológico - Relato de caso

The term "myiasis" refers to human and animal parasites caused by fly larvae. The clinical manifestations of myiasis are not specific, they vary according to the area of the body involved and the species of fly. It is strongly associated with poor oral hygiene and is seen in people with predisposing conditions, such as lack of lip sealing due to malocclusion, tooth extraction, decreased body resistance, malnutrition, open-mouth breathing (especially during sleep), alcoholism, senility, neurological disorder, hemiplegia and facial trauma. The present work describes the particularities of diagnosis and treatment of a case of oral myiasis. A 17-year-old male patient with neurological deficit, totally dependent on his daily life activities. Oral examination revealed poor oral hygiene, presence of periodontitis and lesions in the palate and gingival regions, with swelling and presence of large numbers of larvae. Surgery under local anaesthesia was performed. After exposure of the affected region, the larvae were removed. Sixty-two larvae of various sizes were observed. Early and correct diagnosis of oral myiasis can be easily treated by the dentist by mechanical removal of the larvae with or without the use of local chemicals, with a favourable prognosis

Tissue response evaluation of the mucosa of the tympanic cavity of guinea pigs, when receiving biodegradable implant

PURPOSE:To evaluate the tissue response of the mucosa of the tympanic cavity of guinea pigs, when receiving biodegradable implant.METHODS:A total of 20 male guinea pigs were divided into 2 groups. After paracentesis in both ears, a biodegradable polymer of poly lactic-co-glycolic acid was implanted in only one middle ear. Histological analysis using neutrophil exudate and vascular neoformation (acute inflammation) and fibroblast proliferation and mononuclear inflammatory cells (chronic inflammation) as parameters was performed after 10 and 30 days of survival (groups 1 and 2, respectively).RESULTS:Four ears in group 1 and 7 in group 2 had an increase of neutrophil exudate. Vascular neoformation occurred in ears with or without the implant, in both groups. Fibroblast proliferation and mononuclear inflammatory cells (lymphocytes and macrophages) increased in ears with implant in group 2.CONCLUSION:The tissue response by histological analysis of the mucosa of the tympanic cavity of guinea pigs, when receiving biodegradable implant, showed no statistically significant difference between ears with or without the implant.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Department of OtorhinolaryngologyFederal University of Minas Gerais Faculty of PharmacyFederal University of Minas GeraisUSP Faculty of Medicine of Ribeirao PretoUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Department of Otorhinolaryngology and Head and Neck SurgeryFederal University of São PauloFederal University of São Paulo Medical SchoolUNIFESP, EPM, Department of OtorhinolaryngologyUNIFESP, EPM, Department of Otorhinolaryngology and Head and Neck SurgeryUNIFESP, Medical SchoolSciEL

Sarcopenia and atherosclerotic occlusive disease: how much we know and what we need to know about this association?

Purpose/Background: Sarcopenia (decrease of muscle mass and function) has been linked with atherosclerosis [1]. The EWGSOP2 updated consensus, uses low muscle strength as the primary indicator of sarcopenia [2]. It is acknowledged that strength is better than mass for predicting adverse outcomes [2]. Handgrip strength (HGS) is a simple assessment to estimate overall muscular strength [3]. and is associated with cardiovascular mortality [4]. Objective: Analyze the relationship between HGS and atherosclerotic disease (carotid artery disease + lower extremity artery disease). Methods: Prospective observation study was conducted from January to December 2019. The clinical and demographic data was recorded. Isometric HGS was measured with an adjustable handheld dynamometer (Jamar The higher value of each arm was used to classify the patient as sarcopenic or non-sarcopenic. Definition of sarcopenia: HGS <30 kgf in men and <20 kgf in women [5]. Results: 94 patients (aged 44–86 years) were analyzed: 64 sarcopenic and 30 non sarcopenic. Groups differed in the prevalence of diabetes and smoking status (Table 1). No differences were found in the carotid parameters analyzed (Table 1). There was, a difference in the prevalence of chronic limb-threatening ischemia (CLTI) in sarcopenic versus non-sarcopenic group (23.44% versus 6.67% p = 0.046). Importantly, binary logistic regression showed that diabetes (p = 0.014), and HGS (p = 0.027) have a significant effect on CLTI (Table 2). Conclusions: No relationship was found between sarcopenia (measured by HGS) and carotid atherosclerosis, differing from other authors [1,6]. In this study, sarcopenic had a higher incident of diabetes and CLTI. Sarcopenia and diabetes are reciprocally related and may share a similar pathogenetic pathway [7

Caracterização físico-química de complexos de insulina: dimetil-beta-ciclodextrina e insulina: hidroxipropil-beta-ciclodextrina e avaliação da influência do tipo de complexo na produção de microesferas biodegradáveis

The main stage in the linking and activation of the specific receptors by the insulin is the dissociation of this peptide hexamers, normally present in pharmaceutical formulations, in the monomeric active form. Because of this, the use of different cyclodextrins as adjuvants in the formulations containing insulin has been explored and the realized studies have demonstrated that the cyclodextrins can increase the absorption of the insulin mainly by reducing the ability of insulin oligomerization in aqueous media. In this work, complexes of INS:HP-beta-CD and INS:DM-beta-CD have been characterized by the use of isothermal calorimetry titration (ICT) and dynamic scattering of light. By means of ICT, the thermodynamic parameters of interaction between insulin and the cyclodextrins have been determined, and it was observed that the complexation occurs with an increase of entropy for both systems. The experiments of dynamic scattering of light have not showed reduction in the size of insulin particles, which could indicate the dissociation of insulin hexamers after the complexation with cyclodextrins. Then, the INS: HP-beta-CD and INS:DM-beta-CD complexes were encapsulated in PLGA microspheres. These systems were characterized and it was not observed any significant difference in the microspheres diameter, but a considerable increase in the hormone loading after the complexation with HP-beta-CD and DM-beta-CD was shown.A etapa principal na ativação e ligação da insulina ao seu receptor é a dissociação dos hexâmeros do hormônio, normalmente presente nas preparações farmacêuticas, para a forma monomérica bioativa. A utilização de diferentes ciclodextrinas (CDs) como adjuvantes em formulações contendo insulina vem sendo explorada e os estudos realizados demonstram que estas substâncias podem aumentar a absorção da insulina principalmente por diminuírem sua capacidade de formar dímeros e hexâmeros em meio aquoso. No presente trabalho, complexos de insulina:hidroxipropil-beta-ciclodextrina (INS:HP-beta-CD) e insulina:dimetil-beta-ciclodextrina (INS:DM-beta-CD) foram caracterizados utilizando técnicas de titulação calorimétrica isotérmica e espalhamento dinâmico de luz. Por meio da titulação calorimétrica foram determinados os parâmetros termodinâmicos de interação entre a insulina e as CDs utilizadas, sugerindo que o mecanismo de complexação ocorre com aumento de entropia para ambos os sistemas. Os experimentos de espalhamento dinâmico de luz não indicaram diminuição do diâmetro hidrodinâmico das espécies moleculares de insulina após a complexação com as CDs. Os complexos INS:HP-beta-CD e INS:DM-beta-CD foram encapsulados em microesferas (MEs) de PLGA 50:50. A caracterização das MEs obtidas revelou aumento considerável na taxa de encapsulamento de insulina quando complexada com as CDs sem que ocorresse diferença significativa no diâmetro das partículas em função da complexação

Design of a school randomized trial for nudging students towards healthy diet and physical activity to prevent obesity:PAAPAS Nudge study protocol

Submitted by Janaína Nascimento ([email protected]) on 2019-06-26T13:41:43Z No. of bitstreams: 1 ve_Cunha_Diana_etal_INI_2017.pdf: 188285 bytes, checksum: 9c5af1590f81759ea357050b01c74cce (MD5)Approved for entry into archive by Janaína Nascimento ([email protected]) on 2019-06-26T14:10:20Z (GMT) No. of bitstreams: 1 ve_Cunha_Diana_etal_INI_2017.pdf: 188285 bytes, checksum: 9c5af1590f81759ea357050b01c74cce (MD5)Made available in DSpace on 2019-06-26T14:10:20Z (GMT). No. of bitstreams: 1 ve_Cunha_Diana_etal_INI_2017.pdf: 188285 bytes, checksum: 9c5af1590f81759ea357050b01c74cce (MD5) Previous issue date: 2017State University of Rio de Janeiro. Social Medicine Institute. Department of Epidemiology. Rio de Janeiro, RJ, Brazil.State University of Rio de Janeiro. Social Medicine Institute. Department of Epidemiology. Rio de Janeiro, RJ, Brazil.State University of Rio de Janeiro. Social Medicine Institute. Department of Epidemiology. Rio de Janeiro, RJ, Brazil / Brazilian Navy. Naval Academy. Department of Physical Education and Sports. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca. Departamento de Epidemiologia e Métodos Quantitativos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.State University of Rio de Janeiro. Social Medicine Institute. Department of Epidemiology. Rio de Janeiro, RJ, Brazil.Fluminense Federal University. Institute of Collective Health. Department of Epidemiology and Biostatistics. Niterói, RJ, Brazil.State University of Rio de Janeiro. Social Medicine Institute. Department of Epidemiology. Rio de Janeiro, RJ, Brazil.Fluminense Federal University. Institute of Collective Health. Department of Epidemiology and Biostatistics. Niterói, RJ, Brazil.State University of Rio de Janeiro. Nutrition Institute. Department of Social Nutrition. Rio de Janeiro, RJ, Brazil.State University of Rio de Janeiro. Nutrition Institute. Department of Social Nutrition. Rio de Janeiro, RJ, Brazil.University of Copenhagen. Department of Food Science. Copenhagen, Denmark.Federal University of Rio de Janeiro. Department of Social and Applied Nutrition. Rio de Janeiro, RJ, Brazil.State University of Rio de Janeiro. Social Medicine Institute. Department of Epidemiology. Rio de Janeiro, RJ, Brazil.Objective: To evaluate the effectiveness of nudge activities at school on the students’ body mass index (BMI). Design: School-based factorial randomized community trial. Setting: Eighteen public schools in the municipality of Duque de Caxias, metropolitan area of Rio de Janeiro, Brazil. Participants and intervention: The 18 schools will be randomized into 4 group arms: group 1—control (without any activity); group 2—will receive educational activities in the classroom; group 3—will receive changes in the school environment (nudge strategies); group 4—will receive educational activities and changes in the school environment. Activities will occur during the 2018 school-year. Main outcomemeasure(s): The primary (BMI) and secondary (body fat percentage) outcomes will be assessed at baseline and after the study using a portable electronic scale with a segmental body composition monitor. The height will be measured by a portable stadiometer. Analysis: Statistical analyses for each outcome will be conducted through linear mixed models that took into account the missing data and cluster effect of the schools. Abbreviations: BMI = body mass index, CONSORT = Consolidated Standards of Reporting Trials, PAAPPAS = Portuguese abbreviation of parents, students, community health agents and teachers for healthy eating, Rec24-h = 24-hour recall, SLM = Smarter Lunchrooms Movement

Evaluation of biodegradable implants based on polymer blends: development, characterization and in vitro release studies

Implants prepared with polymer blends [poly (e-caprolactone)-poly(lactide), PCL-PLA] at different rates were developed from microspheres. Approximately 19% of dexamethasone acetate was encapsulated into the microspheres, and it was not dependent on polymer characteristics. DSC studies suggested that there is not any signal of interaction between the polymers and the drug and also no influence of any residual solvent in the microspheres. Infrared analysis indicated the chemical stability of the drug even in the blend matrix. The developed devices present low degradation rate. 34% and 21% of dexamethasone acetate was released from PLA and PCL alone implants at 10 weeks, respectively. Intermediate amounts were released from the devices prepared at different PLA-PCL ratios in such a way that the higher the amount of PCL, the slower was the drug release. This study demonstrates that polymeric drug delivery systems allowed to a prolonged release of dexamethasone acetate in vitro.Colegio de Farmacéuticos de la Provincia de Buenos Aire