OPTIMIZATION OF THE PREPARATION OF LOPERAMIDE-LOADED POLY (L-LACTIDE)NANOPARTICLES BY HIGH-PRESSURE EMULSIFICATION SOLVENT EVAPORATION

The entrapment of loperamide hydrochloride (LPM) in biodegradable poly meric drug carriers such as nanoparticles might enable its passage acr oss the blood-brain barrier. The optimization of the preparation of th e LPM-loaded PLA nanoparticles was performed employing high pressure e mulsification-solvent evaporation. The resulting nanoparticles were ch aracterized by particle size, distribution, thermal analysis, and drug release profiles. The partition of LPM into the organic phase increas ed with an increase in pH of the aqueous phase and with addition of li pophilic surfactants such as sorbitan fatty acid esters, resulting in an increase in the drug entrapment in the nanoparticles. Evaporation o f 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 concentration s. 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, foll owed by a second slower phase. Different drug release profiles from na noparticles can be achieved by addition of sorbitan fatty acid esters, or the employment of different solvents as the organic phase.