For the purpose of enhancement the bioavailability of furosemide (FR), a floating dosage form with controlled release of FR was designed in this study. Because of the lower solubility of active material in the gastric medium, it was first enhanced by preparing an inclusion complex of FR with beta-cyclodextrin (beta-CD) in a 1:1 proportion using the kneading method. Following the design of dosage form, bilayer floating tablets were prepared. After dissolution rate studies were performed using the continuous flow-through cell method, the formulation that provided delivery of active material near the target profile was given to six healthy male volunteer subjects, and in vivo tests were performed. It was determined by radiographs that floating tablets prepared by adding BaSO4 stayed in the stomach for 6 hr. Further, values of the area under the plasma concentration-time curve (AUC) obtained with the floating dosage form were about 1.8 times those of the conventional FR tablet in blood analyses; maximum and minimum plasma concentrations were also found to be between the desired limits. In urine analyses, the peak diuretic effect seen in classical preparations was decreased and prolonged in floating dosage forms. Also, a considerably significant correlation was detected between in vivo results and in vitro data of the dissolution rate, and it was concluded that the modified continuous flow-through cell method is usable for in vitro dissolution rate tests of floating dosage forms.
The purpose of this study was to increase the solubility of furosemide (FR) with inclusion compound of beta-cyclodextrin (beta-CD). The interaction between FR and beta-CD in solution was studied by the solubility method. The phase solubility studies reveal a Bs-type diagram with an inclusion complex of 1:1 molar ratio and a stability constant of 823.5 M(-1). The solid complexes of FR with beta-CD were prepared by using freeze-drying, kneading, and co-precipitation methods. In addition, the physical mixture was prepared for comparison. Inclusion complexation was confirmed by the results from the studies of x-ray diffraction, differential scanning calorimetry, and infrared spectroscopy. The rates of release of the active material from the resulting complexes were determined from dissolution studies using the flow-through cell method. The dissolution rate of FR was significantly enhanced by inclusion of the beta-CD in the formulations. The rate of release of the active material was found to be dependent on the preparation method of the complexes, and the drug prepared by the kneading method was shown to have the fastest dissolution profile compared to the other methods used in this study.
ÖZET
Bu çalışmada pH 1.2 suni mide ortamında çözünürlüğü az olan furosemidin (FR) katı dispersiyonlarıhazırlanarak çözünürlüğünün artırılması düşünülmüş, bu amaçla polivinilpirolidon
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