Studies of floating dosage forms of furosemide: in vitro and in vivo evaluations of bilayer tablet formulations.
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.
Ozdemir
N
N
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ankara, Tandogan-Ankara, Turkey. nozdemir@pharmacy.ankara.edu.tr
Ordu
S
S
Ozkan
Y
Y
D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004232:Diuretics / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004304:Dosage Forms; D005665:Furosemide / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007421:Intestine, Small / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011108:Polymers / Q000493:pharmacokinetics; D011859:Radiography; D013270:Stomach / Q000000981:diagnostic imaging; D013607:Tablets
D004232:Diuretics; D004304:Dosage Forms; D011108:Polymers; D013607:Tablets; D005665:Furosemide