RESUMO
ABSTRACT BCS (Biopharmaceutics Classification System) and BDDCS (Biopharmaceutics Drug Disposition Classification System) were proposed as tools for classifying drugs into four categories. Both systems consider the solubility as an important characteristic for the classification of compounds in drug development and in vivo disposition prediction. Although some results of drug solubility can be found in the literature, the aforementioned characteristic is not entirely clear when considering didanosine (ddI). Based on that, the solubility of ddI was evaluated using equilibrium and intrinsic dissolution methods. For the equilibrium method, excess amount of ddI was added to each media until obtaining a supersaturated solution and the mixture was submitted to agitation at 37 °C. For the intrinsic dissolution method, the drug was compressed into the Wood's apparatus matrix and subjected to dissolution in each media with agitation at 37 °C. The results obtained from the equilibrium method indicated that it was necessary 139.37 mL of pH 1.2 media, 87.72 mL of pH 4.5 media, 12.54 mL of pH 6.8 media, 5.03 mL of pH 7.5 media and 7.65 mL of purified water for drug solubilization. Furthermore, a very fast intrinsic dissolution rate (IDR) was obtained for each media: 0.1 mg/min/cm² (pH 1.2), 0.2 mg/min/cm² (pH 4.5), 0.2 mg/min/cm² (pH 6.8), 0.1 mg/min/cm² (pH 7.5) and 0.1 mg/min/cm² (purified water). Based on these results, ddI can be considered as a highly soluble drug for both equilibrium and intrinsic dissolution methods.
Assuntos
Solubilidade , Biofarmácia , Didanosina/análise , Análise de Sistemas , Preparações Farmacêuticas/classificaçãoRESUMO
A simple, rapid, sensitive and specific reversed-phase high performance liquid chromatographic method involving ultraviolet detection (HPLC-UV) was developed for analysis of didanosine in drug substance and formulated products, tablets. Chromatography was carried out on a pre-packed, Lichrospher 100 Rp-8 (5.0 microm, 250 mm x 4.0 mm) column using 0.01 M sodium acetate solution:methanol (85:15, v/v) adjusted to pH 6.5 with acetic acid as mobile phase at a flow rate of 1.5 ml/min and a 248 nm detection. Hypoxantine was confirmed as the main degradation product. The assay was linear over the concentration range of 50-150 microg/ml (R approximately 0.999). The method was validated for accuracy and precision.
Assuntos
Fármacos Anti-HIV/análise , Didanosina/análise , Calibragem , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Indicadores e Reagentes , Oxirredução , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta , ComprimidosRESUMO
Doenças causadas por vírus representam dificuldades terapêuticas. O conjunto de medicamentos antivirais disponíveis é ainda relativamente pequeno, mas tem crescido nos últimos anos em razäo de enormes investimentos materiais e de talentos: a síndrome da imunodeficiência adquirida é, certamente, o motivo principal dessa procura, mas näo o único. Com a presente atualizaçäo, dedicada a oftalmologistas, o modo de açäo, as aplicaçöes, os efeitos adversos, as apresentaçöes e a posologia dos principais quimioterápicos desse grupo, assim como novidades e perspectivas, säo aqui resumidas