Preparation and Characterization of Polylactic Acid Microspheres Containing Water-Soluble Anesthetics with Small Molecular Weight.

Abstract

Polylactic acid (PLA) microspheres containing water-soluble anesthetics (phenobarbital sodium, pentobarbital sodium, procaine hydrochloride, lidocaine hydrochloride, or dibucaine hydrochloride) with low molecular weight were prepared using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method, and the optimization of preparative conditions was performed. In the microencapsulation of sodium salt anesthetics (phenobarbital sodium, pentobarbital sodium) into PLA matrix, the addition of NaCl (10% (w/v)) into the external aqueous phase and the choice of comparatively high concentration of PLA (16% (w/v)) in CH 2 Cl 2 significantly improved drug loading efficiency compared to the case when no additives were added to the external aqueous phase, or low PLA concentration (4% (w/v)) in CH 2 Cl 2 was employed in the manufacturing process. The loading efficiency of hydrochloride salt anesthetics (procaine hydrochloride, lidocaine hydrochloride, or dibucaine hydrochloride) in PLA microspheres, in constract, was dramatically improved using the alkalic buffer solution as the external aqueous phase. The mean volume diameter was obtained in the region of 2%-30 μm and normal distribution for prepared microspheres in all cases. PLA microspheres containing 10% (theoretical) of various anesthetics exhibited so-called burst releases, but, some portion of the loaded anesthetics still remained in the microspheres at 7 d