Description:
The purpose was to improve the wetting and dissolution rate of repaglinide, a poorly water-soluble drug, by using controlled precipitation (CP) technology.Nanoparticles were produced by controlled precipitation with water as the antisolvent. First, the drug with or without excipients was dissolved in 1,3 dioxolane. The excipients investigated included hypromellose (HPMC E5), polyvinyl pyrrolidone (PVP K15) and polyvinyl alcohol (PVA) The drug/excipient solution was then injected into cold water. Typical drug/excipient ratios ranged from 1:1 to 4:1. Rapid mixing of drug loaded solvent with water produced a high degree of supersaturation resulting in fast rates of nucleation and precise control of the precipitation process. Organic solvent was removed from the dispersion by vacuum distillation. Dried powders were obtained from the aqueous dispersion by freezing and lyophilization. The physicochemical properties of the CP powders and controls were characterized by X-ray diffraction, scanning electron microscopy (SEM), particle size distribution, surface area analysis and dissolution.All powders produced by CP exhibited significantly enhanced dissolution rates as compared to bulk powder. The rate of dissolution of bulk repaglinide was slow; only 30% of the repaglinide was dissolved in 5 minutes. However, the amount dissolved reached 95% in only 5 minutes for the CP repaglinide/HPMC E5 powders. The CP powders were wetted and dissolved immediately upon contact with the dissolution media. The increased dissolution rate of the CP powders was mainly attributed to the amorphous nature of the API, the reduction in particle size and increased surface area.The results successfully demonstrate the use of controlled precipitation to produce nanoparticles of repaglinide with rapid dissolution rates, and this new process is especially applicable to delivery systems containing poorly water soluble drugs. |