Physicochemical Characterization and Dissolution Study of Solid Dispersions of Furosemide with Polyethylene Glycol 6000 and Polyvinylpyrrolidone K 30

Solid dispersions traditionally have been used as effective methods to improve the dissolution properties and bioavailability of poorly water-soluble drugs. The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug, furosemide, by a solid dispersion technique. Solid dispersions were prepared using polyethylene glycol 6000 (PEG 6000) and polyvinylpyrrolidone K30 (PVP K30) in different drug-to-carrier ratios. Dispersions with PEG 6000 were prepared by fusion-cooling and solvent evaporation, while dispersions containing PVP K30 were prepared by solvent evaporation technique. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, powder X-ray diffraction, and FTIR spectroscopy. The aqueous solubility of furosemide was favored by the presence of both polymers. Solid state characterizations indicated that furosemide was present as an amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure furosemide, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. Solid dispersion prepared with PEG showed the most improvement in wettability and dissolution rate of furosemide. Even physical mixtures of furosemide prepared with both polymers also showed better dissolution profiles as compared with that of pure furosemide. Tablets prepared using solid dispersions showed significant improvement in the release profile of furosemide as compared with conventional tablets prepared using furosemide without PEG or PVP. e-mail: raka_77us@yahoo.com and therapeutic efficacy of drugs in dosage forms. The term “solid dispersion” refers to the dispersion of one or more active ingredients in an inert carrier or matrix in the solid state prepared by the melting, solvent, or melting solvent methods (6). A solid dispersion technique has been used by various researchers who have reported encouraging results with different drugs (7). The mechanisms for the enhancement of the dissolution rate of SDs have been proposed by several investigators. A molecular dispersion of drug in polymeric carriers may lead to particle size reduction and surface area enhancement, which result in improved dissolution rates. Furthermore, no energy is required to break up the crystal lattice of a drug during the dissolution process, and there is an improvement in drug solubility and wettability due to the surrounding hydrophilic carriers (8). Reduction or absence of aggregation and agglomeration may also contribute to increased dissolution. The method of preparation and the type of the carrier used are important influences on the properties of such solid dispersions (9). The methods used to prepare SDs include the melting method, the solvent method, and the solvent wetting method (10). Corresponding author. INTRODUCTION The therapeutic efficacy of a drug product intended to be administered by the oral route depends first of all on its absorption by the gastro-intestinal tract. It is well established that dissolution is frequently the rate-limiting step in the gastrointestinal absorption of a drug from a solid dosage form. The relationship between solution rate and absorption is particularly distinct when considering drugs of low aqueous solubility. Poorly soluble drugs have been shown to be unpredictable and are slowly absorbed as compared with drugs with higher solubility. Several methods that have been employed to improve the solubility of poorly water soluble drugs include increasing the particle surface area available for dissolution by milling (1), improving the wettability with surfactants or doped crystals (2), decreasing crystallinity by preparing a solid dispersion (3), use of inclusion compounds such as cyclodextrin derivatives (4), use of polymorphic forms or solvated compounds (5), and use of salt forms. Solid dispersions (SDs) represent a useful pharmaceutical technique for increasing the dissolution, absorption, diss-15-03-06.indd 17 8/15/2008 12:31:54 PM dx.doi.org/10.14227/DT150308P17