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

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

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

Soybean yield under potassium fertilization in a protected environment / Produtividade da soja sob adubação potássica em ambiente protegido

Most of the areas explored in Brazil with soybean cultivation are in tropical regions, where soil formations with a high degree of weathering and low levels of nutrients predominate. Therefore, the objective was to verify soybean yield under different doses of potassium in a dystrophic Yellow Latosol soil. The experiment was carried out in a greenhouse at the Center for Agricultural and Environmental Sciences, at the Federal University of Maranhão, from March to June 2017. The design was completely randomized with five treatments and five replications, totaling 25 plots. The treatments were 0 kg ha-1, 50 kg ha-1, 100 kg ha-1, 200 kg ha-1, and 300 kg ha-1 of K2O, using potassium chloride as a source. The soybean cultivar used was FT4183IPRO, and the results obtained were submitted to the Shapiro-Wilk test to verify normality, the Levene test to verify homogeneity, and the analysis of variance by the F test, when significant the test was used. Tukey, at 5% probability for comparison of means. Potassium fertilization only had a significant effect on MSPA, in which there was also a high correlation between this variable and the grain quantity variable and yield with grain quantity and grain weight. Since the low productivity was due to the poor dispersion of the fertilizer in the pots, causing salinity to the environment

Reconstrução de osso mandibular associado a enxerto autógeno particulado: relato de caso: Mandibular reconstruction associated with particulate autogenous graft: a case report

A atrofia mandibular leva a uma diminuição de massa óssea, e aumento da quantidade de osso cortical, o que torna o osso mais vulnerável a fraturas. Vários métodos de tratamento para fratura de mandíbula atrófica são propostos na literatura, todavia, a redução aberta e fixação interna com placas 2.4 do sistema locking tem sido o tratamento de escolha da atualidade, sempre que a condição do paciente permita abordagem cirúrgica. Este trabalho tem como objetivo relatar um caso de sequela de fratura em mandíbula atrófica em que o paciente relatou dificuldade a mastigação, fonação, e que já havia sido submetido a dois procedimentos cirúrgicos para tratar a fratura, ambos com insucesso. Foi realizada uma nova intervenção cirúrgica de fixação interna rígida, por meio de um acesso extra bucal, com placas e parafusos do sistema locking 2.4, seguido de enxerto imediato de fíbula

Sistemas de transporte de drogas para o segmento posterior do olho: bases fundamentais e aplicações Drug delivery systems for the posterior segment of the eye: fundamental basis and applications

As doenças do segmento posterior do olho são responsáveis pela maioria dos casos de cegueira irreversível no mundo inteiro. Este cenário estimula o desenvolvimento de novas modalidades de tratamento para estas doenças. O sucesso no tratamento visa, essencialmente, o transporte de doses efetivas de drogas diretamente para os locais a serem tratados. Devido às dificuldades encontradas no transporte de drogas para o segmento posterior do olho, pesquisas têm sido realizadas no sentido de desenvolver sistemas de administração intra-oculares que permitam liberar concentrações terapêuticas das drogas por período prolongado. Tais sistemas podem proporcionar inúmeras vantagens, como: aumentar a biodisponibilidade e a concentração local da droga, atingir especificamente um tipo de tecido ou célula, reduzir a freqüência de injeções intra-oculares. Tais vantagens podem aumentar o conforto do paciente e reduzir as complicações observadas com a utilização das injeções intra-oculares. Diferentes sistemas de transporte de drogas têm sido desenvolvidos com as finalidades acima descritas. Estes sistemas podem ser compostos por polímeros biodegradáveis ou não-biodegradáveis ou serem formulações lipídicas. Os sistemas de transporte de drogas são representados, principalmente, pelas micro e nanopartículas e pelos implantes, sendo eles compostos por diferentes polímeros; pelos lipossomos, que são compostos por lípides e emulsionantes; e pela iontoforese, que se baseia na aplicação de corrente elétrica. Nesta revisão, as principais características dos diferentes sistemas de transporte de drogas serão descritas, expondo suas potencialidades de aplicação clínica.<br>The diseases of the posterior segment of the eye are responsible for most cases of irreversible blindness worldwide. These conditions stimulate the development of new modalities of treatment for vitreoretinal diseases. The success in the treatment aims, mainly, the delivery of effective doses of pharmacological agents directly to the target sites. Because of the difficulties in delivering drugs to the posterior segment of the eye, the development of intraocular delivery systems that allow the delivery of therapeutic concentrations of drugs for long periods are being studied. These systems offer many advantages, such as increase in drug bioavailability, obtaining constant and sustained drug release, to achievement of elevated local concentrations of drugs without systemic side effects, targeting one specific tissue or cell type, reducing the frequency of intraocular injections. These advantages can increase the comfort of the patient and reduce the complications observed with intraocular injections. Several drug delivery systems are being developed with the above described purposes. These systems may be prepared with biodegradable or non-biodegradable polymers or they may be lipid formulations. The drug delivery systems are represented, mainly, by micro- e nanoparticles and implants, composed of different polymers; by liposomes, which are made of lipids and surfactants; and by iontophoresis, that is based on the application of an electric current. In this review, the main characteristics of the different drug delivery systems will be shown, with their potentialities of clinical application

Radiolabeling of cidofovir with technetium-99m and biodistribution studies

Radiolabeling cidofovir with technetium-99m (99mTc-CDV) is an innovative procedure that enables real-time monitoring of the drug. Essays were performed in vitro, showing high radiolabel stability within 24 h. Blood clearance, biodistribution studies, and scintigraphic images were performed in healthy mice in order to evaluate the profile of the drug in vivo. 99mTc-CDV showed biphasic blood circulation time and significant kidney uptake, indicating that 99mTc-CDV is preferentially eliminated by the renal route. Bones also showed important uptake throughout the experiment. In summary, cidofovir was successfully labeled with technetium-99m and might be used in further studies to track the drug