Another surface active lipid excipient class that has shown significant promise for application in solid dispersion formulations is the block copolymer (55-59), various grades of which are commercially available as poloxamers (Pluronics®). Ho et al. (56) reported that the dissolution rate of nifedipine from a solid dispersion in Pluronic F-68 was positively correlated with the Pluronic F-68:nifedipine concentration ratio. In another study, the in vitro dissolution rate in pH 6.8 buffer and the bioavailability in dogs of a poorly water-soluble drug, ABT-963, were increased relative to a conventional capsule formulation containing drug-excipi-ent granules by a solid dispersion formulation Pluronic-F68 prepared by solvent evaporation or filled into capsules in the molten state (58). At a concentration of approximately 7.5% w/w, the drug formed a eutectic mixture with Pluronic F-68, which thermal analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), and elemental mapping demonstrated to be comprised of crystalline ABT-963 and Pluronic F-68. More recently, Yin et al. (59) prepared a spray-dried formulation of the water-insoluble drug, BMS-347070, which resulted in rapid drug absorption and bioavailability in dogs comparable to that of a solution formulation. The drug was dissolved in acetone or methylene chloride along with Pluronic F-127 and spray-dried to form a dispersion of nanosized crystalline drug material within a crystalline, water-soluble matrix. The authors hypothesized that the polyethylene oxide segments of Pluronic F-127 crystallized, while the polypropylene oxide segments of the excipient remained amorphous, creating a size-restricted domain in which the drug substance formed physically stable nanocrystals.
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