Comparison of Nicotinamide, Ethylurea and Polyethylene Glycol as Carriers for Nifedipine Solid Dispersion Systems.

Abstract

The most prevalent means for producing solid dispersions of nifedipine, a poorly water-soluble drug, are the solvent based processes that bring problems of environmental and health. We have investigated the preparation of solid dispersions of nifedipine (mp 173 degrees C) by the fusion method, using nicotinamide, ethylurea, polyethylene glycol (PEG) 6000 and hydroxypropylmethylcellulose (HPMC) as carriers. All these solid dispersions were obtained by cooling at room temperature after heating at 140 degrees C for 15 min. As a single carrier, nicotinamide, ethylurea and PEG were used because nifedipine dissolved in their fused liquids. Compared with the physical mixtures, the solid dispersions with ethylurea or PEG led to a higher dissolution rate of the drug, whereas the difference in drug release between the physical mixtures and the solid dispersions with nicotinamide was not clear. This peculiarity might be due to the high solubilizing effect of nicotinamide for the drug. The fused mixtures of nicotinamide-, ethylurea- or PEG-HPMC were utilized as combined carriers. HPMC dissolved in the fused liquids of nicotinamide or ethylurea, which was effective in forming the amorphous nifedipine in solid dispersions. This resulted in not only the enhanced dissolution rate but also the supersaturation behavior of nifedipine. Further, for the nicotinamide-HPMC system, the supersaturation level of nifedipine increased with an increase in the HPMC content of solid dispersions. Nicotinamide was more applicable than ethylurea and PEG for preparation of the fused dispersions of nifedipine.

Physicochemical considerations in the preparation of amorphous ritonavir–poly(ethylene glycol) 8000 solid dispersions

“…In the solid state, PEG–drug interactions resulting in the formation of solid solutions have also been reported 6,25,26. The formation of a solid solution leads to the destruction of the crystal lattice of the drug and a partial disruption of the lattice of the carrier.…”

Flocculated amorphous itraconazole nanoparticles for enhancedin vitrosupersaturation andin vivobioavailability

“…A higher surface area increases the dissolution rate, while an amorphous form allows for high supersaturation of the metastable state (up to 1,600 times 4-7 ) relative to the crystalline equilibrium solubility 5,[8][9][10] . Amorphous solid solutions and dispersions have been created by numerous techniques including co-grinding 10,11 , solvent evaporation [12][13][14][15][16] hot-melt extrusion 14,17,18 , and antisolvent precipitation 9 . However, typically the amorphous form is stabilized against crystallization with high quantities (>50% of the formulation) of polymers such as hydroxypropylmethylcellulose (HPMC) and poly(vinylp yrolidone) 4,5,7,10,11,13,14,16,[19][20][21][22][23] .…”

Flocculated Amorphous Nanoparticles for Highly Supersaturated Solutions

“…Solubilities of amorphous drugs may reach 1,600-times that of the crystalline form (4)(5)(6)(7). Typically, amorphous solid solutions or dispersions of drugs, stabilized by high glass transition (T g ) polymers, are formulated by co-grinding (8), solvent evaporation (9)(10)(11)(12)(13), or hot melt extrusion (14,15). Amorphous formulations, however, have a tendency to crystallize during dissolution (16).…”