Abstract:

Objective(s): The purpose of the current study was to assess the feasibility of microspheres from biocompatible polymer for oral bioavailability (BA) enhancement of potent sulfonamide- type loop diuretic- Furosemide - which used in the treatment of congestive heart failure, caused edema, cirrhosis, renal disease and as an adjunct in acute pulmonary edema. The comparatively poor and inconstant BA of furosemide, which occurs site-specifically in the stomach and upper small intestine, has been ascribed to the poor dissolution of furosemide. Materials and Methods: In attempt to enhance the drug BA, poly (dl-lactic-co-glycolic acid) (PLGA) microspheres of furosemide were obtained using solvent-evaporation method and the carrier characteristics were investigated subsequently. Results: The in vivo performance of optimum formulation was assessed by pharmacokinetic evaluation of drug after orally administration of free and loaded in microspheres to rats (4 mg/Kg). For this reason, the concentration of drug in plasma was measured by a new developed and sensitive method of HPLC. Acceptable drug loading and encapsulation efficiency of microspheres were obtained to be 70.43 and 85.21 %, respectively. Microspheres provided improved pharmacokinetic parameters (Cmax = 147.94 ng/ml, Tmax = 1.92 hr) in rats as compared with pure drug (Cmax = 75.69 ng/ml, Tmax = 1.5 hr). The obtained AUC of drug in microsphere was 10 fold higher than of the free drug. Conclusion: The results showed that the prepared microspheres successfully improved BA of the poorly water-soluble drug effectively.

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