Design and optimization of self-microemulsifying drug delivery system (SMEDDS) of felodipine for chronotherapeutic application

The objective of this research work was to design, develop and optimize the self micro-emulsifying drug delivery system (SMEDDS) of Felodipine (FL) filled in hard gelatine capsule coated with polymer in order to achieve rapid drug release after a desired time lag in the management of hypertension. Microemulsion is composed of a FL, Lauroglycol FCC, Transcutol P and Cremophor EL. The optimum surfactant to co-surfactant ratio was found to be 2:1. The resultant microemulsions have a particle size in the range of 65-85 nm and zeta potential value of -13.71 mV. FL release was adequately adjusted by using pH independent polymer i.e. ethyl cellulose along with dibutyl phthalate as plasticizer. Influence of formulation variables like viscosity of polymer, type of plasticizer and percent coating weight gain was investigated to characterize the time lag. The developed formulation of FL SMEDDS capsules coated with ethyl cellulose showed time lag of 5-7 h which is desirable for chronotherapeutic application.

O objetivo desse trabalho de pesquisa foi planejar, desenvolver e otimizar sistema de liberação de fármaco auto-microemulsificante(SMEDDS) de felodipino (FL) em cápsulas de gelatina dura revestidas com polímero, a fim de obter liberação rápida após tempo desejado no manejo da hipertensão. A microemulsão é composta de FL, lauroglilcol FCC, Transcutol P e Cremophor EL. A proporção ótima de tensoativo e de co-tensoativo foi de 2:1. As microemulsões resultantes têm tamanho de partícula na faixa de 65-85 nm com potencial zeta de -13,71 mV. A liberação de FL foi ajustada adequadamente, utilizando-se polímero independente de pH, como etilcelulose com ftalato de dibutila como plastificante. A influência das variáveis da formulação, como viscosidade do polímero, tipo de plastificante e ganho percentual de peso do revestimento foi investigada para caracterizar o intervalo de tempo de liberação. A formulação de cápsulas de FL SMEDDS revestidas com etilcelulose mostrou intervalo de tempo de liberação de 5 a 7 horas, o que é desejável para uma aplicação cronoterapêutica.

Study of thermal behavior of phytic acid

Phytic acid is a natural compound widely used as depigmenting agent in galenic cosmetic emulsions. However, we have observed experimentally that phytic acid, when heated to 150 ºC for around one hour, shows evidence of thermal decomposition. Few studies investigating this substance alone with regard to its stability are available in the literature. This fact prompted the present study to characterize this species and its thermal behavior using thermal analysis (TG/DTG and DSC) and to associate the results of these techniques with those obtained by elemental analysis (EA) and absorption spectroscopy in the infrared region. The TG/DTG and DSC curves allowed evaluation of the thermal behavior of the sample of phytic acid and enabled use of the non-isothermal thermogravimetric method to study the kinetics of the three main mass-loss events: dehydration I, dehydration II and thermal decomposition. The combination of infrared absorption spectroscopy and elemental analysis techniques allowed evaluation of the intermediate products of the thermal decomposition of phytic acid. The infrared spectra of samples taken during the heating process revealed a reduction in the intensity of the absorption band related to O-H stretching as a result of the dehydration process. Furthermore, elemental analysis results showed an increase in the carbon content and a decrease in the hydrogen content at temperatures of 95, 150, 263 and 380 °C. Visually, darkening of the material was observed at 150 °C, indicating that the thermal decomposition of the material started at this temperature. At a temperature of 380 °C, thermal decomposition progressed, leading to a decrease in carbon and hydrogen. The results of thermogravimetry coupled with those of elemental analysis allow us to conclude that there was agreement between the percentages of phytic acid found in aqueous solution. The kinetic study by the non-isothermal thermogravimetric method showed that the dehydration process occurred in two stages. Dehydration step I promoted a process of vaporization of water (reaction order of zero), whereas dehydration step II showed an order of reaction equal to five. This change in reaction order was attributed to loss of chemically bonded water molecules of phytic acid or to the presence of volatile substances. Finally, the thermal decomposition step revealed an order of reaction equal to one. It was not possible to perform the kinetic study for other stages of mass loss.

O ácido fítico é um composto natural muito utilizado como despigmentante em emulsões cosméticas magistrais. No entanto, observou-se experimentalmente que o ácido fítico, quando aquecido a 150 °C durante cerca de uma hora, mostra evidências de decomposição térmica e que poucos estudos envolvendo essa espécie, isoladamente quanto a sua estabilidade, estão disponíveis na literatura. Esse fato motivou o estudo de caracterização e de comportamento térmico dessa espécie, empregando a análise térmica (TG/DTG e DSC) e associando os resultados obtidos com aqueles de análise elementar (AE) e espectroscopia de absorção na região do infravermelho. As curvas TG/DTG e DSC permitiram avaliar o comportamento térmico da amostra de ácido fítico e, com isso, foi possível estudar, pelo método termogravimétrico não isotérmico, a cinética dos três principais eventos de perda de massa, o de desidratação I, desidratação II e de decomposição térmica. A associação das técnicas de espectroscopia de absorção no infravermelho e análise elementar permitiu avaliar os produtos intermediários da decomposição térmica do ácido fítico. Os espectros no infravermelho de amostras isoladas durante o aquecimento evidenciaram a diminuição de intensidade da banda de absorção relativa ao estiramento do grupo O-H como consequência do processo de desidratação. Também, os resultados de análise elementar indicaram que nas temperaturas de 95, 150 e 263 ºC houve aumento no teor de carbono e diminuição do teor de hidrogênio. Visualmente, observou-se o escurecimento do material a 150 ºC, indicando que a decomposição térmica do material iniciou-se nessa temperatura. Na temperatura de 380 ºC, a diminuição do teor de carbono e hidrogênio foi devido ao avanço do processo de decomposição térmica. Os resultados da termogravimetria juntamente com aqueles da análise elementar permitiram concluir que há concordância entre as percentagens de ácido fítico encontrado na solução aquosa. O estudo cinético pelo método termogravimétrico não isotérmico mostrou que o processo de desidratação ocorreu em duas etapas. Na etapa I da desidratação ocorreu um processo de vaporização de água (ordem de reação igual a zero). Na etapa II da desidratação foi encontrada uma ordem de reação igual a cinco. Essa mudança na ordem de reação foi atribuída à perda de moléculas de água quimicamente ligada, ao ácido fítico ou à presença de substâncias voláteis. Finalmente, na etapa de decomposição térmica foi observado que a ordem da reação foi igual a um. Para as outras etapas de perda de massa não foi possível a realização do estudo cinético.

Desenvolvimento e Teste Preliminar da Estabilidade de formulações cosméticas acrescidas de extrato comercial de Trichilia catigua Adr. Juss (e) Ptychopetalum olacoides Bentham / Development and Preliminary Stability Testing of cosmetic formulations containing the commercial extract of Trichilia catigua Adr. Juss and Ptychopetalum olacoides Bentham

O presente estdo apresenta etapas de desenvolvimento de emulsões cosméticas, contendo 5% do extrato comercial de Trichilia catigua Adr. Juss (e) Ptychopetalum olacoides Bentham. Desenvolveram-se 14 formulações-teste e avaliou-se a obtenção de emulsões macroscopicamente estáveis, com valores de viscosidade aparente variados, pH compatível com o da pele e características organolépticas adequadas, por meio dos Testes de Estabilidade Preliminar e Acelerada. Estas formulações foram divididas em dois grupos: um com emulsões fluidas e outro com emulsões mais viscosas. Após análise, oito formulações-teste foram consideradas aptas para serem submetidas ao Teste de Estabilidade Preliminar. Após os ensaios, cinco formulações-teste foram selecionadas para o Teste de Estabilidade Acelerada. Os ensaios foram conduzidos em condições de armazenamento, de luminosidade e de temperatura extremas. Ao final do estudo, duas formulações-teste foram consideradas aprovadas por apresentarem os perfis mais estáveis durante o estudo, sendo ambas, emulsões fluidas constituídas de ceras auto-emulsionantes e 0,3% p/p de um polímero natural,e uma delas adicionada também de 2,0% lecitina de soja.

Nanoemulsão contendo 7-cetocolesterol (LDE/7KC) promove inibição do crescimento de malanoma em camundongos e aumento de sobrevida / A 7-ketocholesterol containing-nanoemulsion (LDE/7KC) inhibits growth of melanoma tumor in mice and increases survival rate

7-cetocoleterol (7KC) é um oxisterol conhecido por inibir a proliferação celular e por ser citotóxico. Uma nanoemulsão contendo 7KC (LDE/7KC) demonstrou efeito anti-proliferativo sobre as linhagens RPMI 8226 (mieloma) e melanoma (B16F10), in vitro. Sendo preferencialmente captada via receptores de LDL. No presente trabalho, avaliamos, in vivo, a cinética plasmática, biodistribuição e ação anti-tumoral em camundongos portadores de melanoma. A nanoemulsão dirigiu-se principalmente no fígado e ao tumor, demonstrando direcionamento a tecidos com alta expressão de receptores para LDL. LDE/7KC promoveu uma redução superior a cinqüenta por cento do tamanho do tumor, que apresentou maior área de necrose e menor quantidade de vasos e aumentou a sobrevida dos camundongos, sem causar toxicidade.

7-ketocholesterol (7KC) is an oxysterol known to inhibit cell proliferation and to be cytotoxic. A nanoemulsion containing-7KC (LDE/7KC) was shown to had antiproliferative effects on RPMI 8226 myeloma cell line and melanoma (B16F10), in vitro. This particle is taken up mainly by LDL receptors. Here we have evaluated the plasma kinetic, biodistribution and the anti-tumoral action of LDE/7KC in melanoma bearing mice. The nanoemulsion accumulated in the liver and tumor, tissues with a high expression of LDL receptors. LDE/7KC promoted a tumor size reduction over fifty percent. A increased necrosis area and a decreased amount of blood vessels was found. A increased survival rate was observed, together with a lack of toxicicity.

Sustained release of flufenamic acid from drug adsorbed emulsions

Sustained release flufenamic acid O/W dry adsorbed emulsions were prepared. The influence of type of oil [sesame oil and linseed oil], concentration of hydrophilic surfactant [2 and 3% of polysorbate 80] and type of hydrophilic adsorbent [Avicel PH 101 and Aerosil 200] on the tapped density [g/ml], void, flowability of flufenamic acid dry adsorbed emulsions and the percentage of drug released after 8 hours from the emulsions were evaluated using a 23 factorial design. It was found that, tapped density as well as void of flufenamic acid dry absorbed emulsion particles were affected by the type of both oil and hydrophilic adsorbent. While, the flowability of dry emulsions was only affected by the type of hydrophilic adsorbent. The most important factor that affected the drug release from dry adsorbed emulsions was the type of hydrophilic adsorbent

Evaluation of chlorpheniramine maleate sustained release formulations

Calcium alginate beads of chlorpheniramine maleate [CPM] were prepared and the drug release was studied at different pHs. The bioavailability of CPM from CPM-calcium alginate beads was assessed in rabbits and compared with that from dry adsorbed emulsion previously prepared. DSC and IR studies showed that the drug formed a complex with alginate molecules. Generally, the drug release was faster in alkaline pH [7.4] than in acidic pH [1.2]. The study revealed that CPM-beads were better than CPM-dry adsorbed emulsion as a sustained release formulation. The extent of bioavailability of CPM-beads showed, on equal dose basis, an equivalent therapeutic effect to one dose of regular release CPM

Preparation of albumin microspheres by the emulsification technique

Egg albumin microspheres have been prepared by the emulsification procedure. The most important variables in the production of albumin microspheres have been studied. Increasing the albumin concentration gave rise to an increase in both the mean size and the size distribution of the prepared microsphere due to its effect on the viscosity of the dispersed phase. In order to obtain larger microspheres, relative low stirring speeds have been chosen. Heat was used to denature the albumin, rapid heating seemed to facilitate aggregation of the formed microspheres. In an attempt to control the particle size of the dispersed phase, different concentrations of sorbitan trioleate have been used during the preparation. The presence of excess concentration of drug on the surface of the microspheres resulted in a burst effect for drug release in 0.1 N HCl with up to 25% drug released in 5 minutes. Spermaceti and beeswaxes were included in an effort to slow drug release and to eliminate the initial burst effect. Drug release was found to vary with type and level of wax and the degree of thermal treatment. In vitro drug release profiles were evaluated for the untreated and treated spheres at room temperature and at 80C. In general, the simple incorporation of wax into the microspheres did not provide the desired controlled release of the drug. Thermal treatment of the albumin microspheres, however, resulted in a products which behaved in a different manner during dissolution testing and in general, provided slower release

Controlled release of salbutamol sulphate through dry adsorbed emulsion

Dry Adsorbed Emulsions [DAE[s]] of salbutamol sulphate were prepared and evaluated as novel sustained drug delivery system. The type of oil used in the formulation of the primary W/O emulsion as well as the type of materials added to affect the viscosity of the primary emulsion were found to be the determining factors in controlling the release rate of salbutamol sulphate from its DAE. DAE prepared using cottonseed oil as oil phase gave the slowest release rate followed by liquid paraffin and finally silicone oil. Addition of Al monostearate [AIMS] and methyl cellulose [MC] to increase the viscosity of the primary emulsions decreased the release rate of the drug from its DEA[s]. MC decreased the rate of release of the drug from its DEA but to less extent than AIMS