Studies of Floating Dosage Forms of Furosemide: In Vitro and In Vivo Evaluations of Bilayer Tablet Formulations

Abstract

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.

Formulation and In Vitro Evaluation of Sunflower Oil Entrapped within Buoyant Beads of Furosemide

“…Higher absolute bioavailability in a floating dosage form than from a nonfloating commercial product of furosemide has already been demonstrated in dogs [4]. Improved bioavailability of furosemide from a floating tablet in human volunteers has also been reported [5]. Although single unit dosage forms of furosemide have been extensively investigated, few studies have been reported using multiple unit dosage forms of furosemide [6].…”

Cefuroxime axetil loaded gastroretentive floating tabletsbased on hydrophilic polymers: preparation and in vitro evaluation

“…It then remains buoyant and floats in the gastric fluid, affecting a prolonged gastric residence time (GRT). This floating dosage form is known as a hydrodynamically balanced system (HBS (Ozdemir et al 2000).Hydrodynamically balanced systems can remain in the gastric region for several hours and hence significantly prolong the gastric residence time of drugs. Prolonged gastric retention improves bioavailability, reduces drug waste, and improves solubility for drugs that are less soluble in a high pH environment of small intestine.…”

Formulation and Evaluation of Controlled Release Gastro-Retentive In situ Gel for Diltiazem Hydrochloride

“…From this the requisites to prolong the residence time of such dosage forms in the stomach leads to an important approach including decrease in the density to stimulate floating in the gastric fluids and thus gastro-retentive sustained release dosage form is reached. 2 This new revolution that has been achieved in sustained drug delivery system represents today by floating in situ gel system. In this system, a solution of low viscosity can be easily applied; which upon reaching gastric contents it undergoes polymeric changes; thus producing a viscous in situ gel of density lower than the gastric fluids.…”