RESUMEN
AIM: Binary and ternary complexes with hydroxypropyl-ß-cyclodextrin (HPßCD), using glutamic acid (GA), proline or lysine as the third component, were developed to increase the solubility and the dissolution rate of norfloxacin (NOR). METHODS/RESULTS: Complexation was evaluated by phase solubility studies, obtaining the highest NOR solubility with GA and HPßCD. Thermal analysis suggested that different kinds of interactions occur among NOR, HPßCD and each amino acid, and when the systems were prepared by kneading or by means of freeze-drying technique. Dissolution studies, performed on simulated gastric fluid and subsequent simulated intestinal fluid, showed the highest rate of NOR from NOR-HPßCD-GA. CONCLUSION: NOR:HPßCD:GA was the best approach for improving the bioavailability of NOR.
Asunto(s)
Antibacterianos/farmacocinética , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Norfloxacino/farmacocinética , 2-Hidroxipropil-beta-Ciclodextrina/química , Antibacterianos/administración & dosificación , Antibacterianos/química , Disponibilidad Biológica , Rastreo Diferencial de Calorimetría , Química Farmacéutica , Liberación de Fármacos , Liofilización , Ácido Glutámico/química , Norfloxacino/administración & dosificación , Norfloxacino/química , Solubilidad , beta-Ciclodextrinas/químicaRESUMEN
The aim of this work was to predict the permeability of two model drugs, sulfamerazine (SMR) and indomethacin (INM), and to determine the effect on their apparent permeabilities by complexation with cyclodextrins and/or meglumine or incorporation in microemulsions. Permeation experiments were performed using two-chamber diffusion cells with a new composition of bio-mimetic membrane composed of 80% of Lipoid® S100 and 20% of cholesterol in n-octanol 10% w/w solution, at 37 ± 0.5°C and 14,000 rpm. The predictive capacity of the permeability of passive diffusion absorbed compounds was evaluated using 20 drug standards and showed an exponential correlation between the apparent permeability coefficients (Papp) and the fraction absorbed percentages in humans (Fa%), with an R2 value of 0.67942 and a constant value of - 4.1 ± 0.8. SMR and INM were classified as Class II and I, respectively, according to the Biopharmaceutical Classification System. These drugs were complexed and incorporated in microemulsions. The Fa% from all the drug products was higher than 90%. SMR in the complexes and both drugs in microemulsions were classified as highly soluble. Thus, SMR and INM incorporated in these pharmaceutical products could be classified as Class I.