RESUMO
Hydrochlorothiazide is a common diuretic antihypertensive drug of the thiazide family. Its poor aqueous solubility is one of the reasons for its limited bioavailability after oral administration. This work aimed at the development of a hydrochlorothiazide:ß-cyclodextrin (HTZ:ß-CD) pharmaceutical composition in order to improve water solubility and bioavailability of the drug. The HTZ:ß-CD complexes were prepared by three different methods: spray-drying, freeze-drying and fluid bed. Complexes were characterized by thermal analysis, Fourier transform-infrared (FTIR) spectroscopy, powder X-ray diffractometry, NMR (2D-ROESY), scanning electron microscopy (SEM), particle analysis and intrinsic dissolution. The findings reveal that three binary systems prepared presented better solubility results in comparison with free HTZ. Increased diuretic effect was observed to HTZ:ß-CD obtained by fluid bed in comparison to free drug in rats. Results taken together suggest that pharmacological effect of HTZ in complex was increased by solubility improvement promoted by cyclodextrin.
Assuntos
Diuréticos/química , Diuréticos/farmacologia , Hidroclorotiazida/química , Hidroclorotiazida/farmacologia , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacologia , Animais , Química Farmacêutica , Capacidade de Concentração Renal/efeitos dos fármacos , Masculino , Ressonância Magnética Nuclear Biomolecular , Pós/química , Pós/farmacologia , Ratos , Ratos Wistar , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
A glibenclamida (GLIB) ou gliburida, é um hipoglicemiante oral de segunda geração, da classe das sulfoniluréias, usado sob a forma de comprimidos para tratamento do diabetes mellitus. Variações no tratamento podem ocorrer, devido à baixa solubilidade do fármaco em comprimidos. A comparação de várias formulações de comprimidos piloto com comprimidos do medicamento referência (Daonil®, glibenclamida 5 mg comprimidos, Aventis Pharma Ltda.) foi avaliada por meio do desenvolvimento de um teste de dissolução sem adição de solventes orgânicos ou tensoativos no meio, que mostrou ser discriminativo para as diferentes formulações farmacêuticas propostas. A quantificação de GLIB foi realizada por meio de cromatografia líquida de alta eficiência em fase reversa (CLAE-FR), método previamente validado. A partir de vários ensaios de perfil de dissolução testados comparativamente àquele de comprimidos do medicamento referência, verificou-se o potencial de determinada formulação proposta (f1 4,04 and f2 69,35) como candidata a medicamento genérico no mercado brasileiro.
Glibenclamide (GLIB) or glyburide, a second-generation hypoglycemic agent is used per oral as tablets for the treatment of diabetes mellitus. Much variabilility in the treatment may occur because of the low drug aqueous solubility in tablets dosage forms. This work reports the comparison of several pilot formulation batches with the commercial reference drug dosage form (Daonil®, glibenclamide 5 mg per tablet, Aventis Pharma Ltda.). A feasible dissolution test, developed with no use of organic solvents or surfactants in the medium, showed to be discriminative regarding to different formulations tested. GLIB quantitation was performed by a previously validated reverse-phase high performance liquid chromatography (RP-HPLC). Among several dissolution profiles compared with that of a commercial reference, a potential for a generic candidate was evident (f1 4.04 and f2 69.35) for a proposed solid dosage formulation in the Brazilian market.
