INFLUENCE OF THE PREPARATION METHODS ON THE DRUG-RELEASE BEHAVIOR OF LOPERAMIDE-LOADED NANOPARTICLES

Polylactide (PLA) or poly(lactide-coglycolide) (PLGA) nanoparticles co ntaining loperamide (LPM) were prepared by an incorporation or adsorpt ion method with the objective of developing nanoparticles with a rapid drug release. The use of polymers such as PLA with lower molecular we ights and the addition of sorbitan fatty acid esters (SFAE) for the in corporation led to an almost complete entrapment of LPM in nanoparticl es. Preparation of PLA nanoparticles by adsorption was performed by ad dition of LPM methanol solution before, during and after evaporation o f dichloromethane from the system. The adsorption of LPM onto the nano particles with low molecular weight PLA (m.w. 2000) showed an isotherm with a good correlation to the Langmuir equation. A high amount of LP M can be entrapped or adsorbed in nanoparticles only with low molecula r weights of PLA or PLGA. In the incorporation method, the addition of SFAEs increased drug entrapment. However, in the adsorption method th ey had no effect on nanoparticle drug adsorption. The drug-release pro files from both nanoparticles, prepared by the adsorption and incorpor ation methods, were biphasic with an initial rapid release and a secon d slower release phase, although their initial extents of release were different. The release rates were almost the same for both the adsorp tion and incorporation method without SFAEs. The addition of SFAEs to the adsorption system increased the extent of drug release from nanopa rticles. In conclusion, a rapid loperamide release from nanoparticles can be achieved by use of PLA or PLGA with low molecular weights and i n the adsorption method by the addition of SFAEs.