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Optimization Of The Preparation Of Loperamide-loaded Poly (L-lactide) Nanoparticles By High Pressure Emulsification-solvent Evaporation.

M. Ueda, J. Kreuter
Published 1997 · Chemistry, Medicine

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The entrapment of loperamide hydrochloride (LPM) in biodegradable polymeric drug carriers such as nanoparticles might enable its passage across the blood-brain barrier. The optimization of the preparation of the LPM-loaded PLA nanoparticles was performed employing high pressure emulsification-solvent evaporation. The resulting nanoparticles were characterized by particle size, distribution, thermal analysis, and drug release profiles. The partition of LPM into the organic phase increased with an increase in pH of the aqueous phase and with addition of lipophilic surfactants such as sorbitan fatty acid esters, resulting in an increase in the drug entrapment in the nanoparticles. Evaporation of the organic phase under reduced pressure and the addition of ethanol in the organic phase yielded a high drug entrapment due to the rapid polymer precipitation. The addition of the sorbitan fatty acid esters further increased the drug entrapment even at higher LPM concentrations. The results of thermal analysis suggest that LPM was homogeneously dispersed in the amorphous polymer matrix. The in vitro release of the drug from nanoparticles was biphasic, with a fast initial phase, followed by a second slower phase. Different drug release profiles from nanoparticles can be achieved by addition of sorbitan fatty acid esters, or the employment of different solvents as the organic phase.
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