Comparative in vitro and in vivo evaluations of oral sustained-release formulations of diclofenac sodium in beagle dogs.

PURPOSE: Two sustained release formulations (microspheres and Voltaren SR75) were evaluated for their drug release characteristics in dissolution (in vitro study) and after oral administration to beagle dogs (in vivo study) by HPLC. METHODS: The dissolution study was carried out according to the paddle method and the pharmacokinetic study was conducted using HPLC analysis in a crossover design in six female beagle dogs after oral administration of 75 mg diclofenac sodium (DFS). RESULTS: The dissolution profiles showed 45% release for Voltaren SR75 and around 95% for the microspheres. Oral administration of DFS resulted in AUC(0-24) and Cmax values of 20.4 microg h/mL and 3.04 microg/mL for microspheres and 33.5 microg h/mL and 5.59 microg/mL for Voltaren, respectively. The Tmax was 3.0 h for both formulations. A significant difference in AUC(0-24) and Cmax was observed for DFS absorption from microspheres and Voltaren. CONCLUSIONS: The results from the dissolution assay demonstrated the faster release of diclofenac sodium from microspheres. The bioavailability of DFS in microspheres was about 61% that of Voltaren, for the parameters AUC and Cmax, and they are therefore not bioequivalent to Voltaren in relation to the extent of absorption. However, the rate of drug absorption (Tmax) was similar for the two formulations.

O emprego de sistemas de liberação como estratégia para melhorar as propriedades terapêuticas de fármacos de origem natural: o exemplo da camptotecina e seus derivados / Drug delivery systems as a way to improve the therapeutic properties of natural drugs: the example of camptothecin and its derivatives

As plantas têm sido utilizadas para a obtenção de um grande número de substâncias biologicamente ativas. Entretanto, muitos compostos naturais quando empregados sem qualquer modificação química não resultaram em medicamentos eficazes, por não apresentarem as características desejáveis para administração. Neste sentido, a melhoria das propriedades terapêuticas de compostos isolados de plantas por meio da sua incorporação em sistemas de liberação de fármacos consiste em uma importante estratégia na obtenção de novos medicamentos, na qual ainda existe muito a ser explorado. Tais sistemas são caracterizados por apresentar a capacidade de prolongar e controlar a liberação de substâncias ativas, proteger as moléculas frente à degradação no meio biológico, veicular fármacos hidrofóbicos e reduzir os efeitos colaterais indesejáveis. A camptotecina, um alcalóide proveniente do arbusto Camptotheca acuminata (Descaisne, Nyssaceae), é um fármaco que apresenta elevada atividade antitumoral, cujo mecanismo envolve a inibição da topoisomerase I, uma enzima altamente expressa nos tumores. Entretanto, a utilização deste fármaco na terapêutica foi limitada, durante anos, em virtude de suas características de baixa solubilidade aquosa, elevada instabilidade em meio fisiológico e elevada toxicidade. Neste artigo é realizada uma revisão sobre o potencial terapêutico da camptotecinae seus análogos no tratamento do câncer, dando ênfase aos estudos conduzidos com o intuito de contornar as limitações da administração destes fármacos e que resultaram na melhoria das propriedades terapêuticas. Estratégias como a microencapsulação, nanoencapsulação e solubilização em micelas poliméricas, entre outras, são discutidas e os principais resultados de atividade antitumoral in vitro e in vivo são apresentados.

Evaluation of the hydrophobic drug loading characteristics in nanoprecipitated amphiphilic cyclodextrin nanospheres.

The aim of this work was to evaluate the loading capacity and the association characteristics of the hydrophobic drug progesterone on amphiphilic cyclodextrin nanospheres prepared by the nanoprecipitation method. The colloidal suspensions were prepared in the presence or absence of two different surfactants, Pluronic F68 and Tween 80. The physicochemical characteristics of the nanospheres were assessed using a nanosizer, zetameter, and transmission electron microscope. The physical state of the drug was verified using differential scanning calorimetry (DSC) and x-ray diffraction (XRD) methods. The in vitro progesterone release was investigated at 37 degrees C after dilution of the suspensions in sink conditions. Nanospheres with a mean diameter from 100 to 300 nm and a low degree of polydispersity were prepared from amphiphilic hexanoyl-gamma-cyclodextrin. The progesterone loading capacity was not affected by the formulation parameters tested. The DSC and XRD studies demonstrated the absence of the crystalline domains of progesterone in loaded nanospheres. The DSC studies also demonstrated the presence of interactions between the drug and carrier. The release of the drug from the carrier was extremely rapid and was governed by a partition phenomenon that depends only on the solubility of the drug in the release medium. From these results, we concluded that with this method, the progesterone is molecularly associated at the surface of the cyclodextrin nanospheres, probably through hydrophobic interactions in specific sites. The release profiles obtained can be of value when an improvement in the bioavailability of the drug is desired.