Background: The local anesthetic drugs, especially ropivacine, were considered favorable
analgesia for postoperative management because of their effective local pain relief and low adverse effects.
However, the short half-life and the resulting in bolus doses lead to the indistinctive improvement
of these drugs in postoperative pain relief. Therefore, the ropivacine microspheres with sustained release
and low initial burst release were anticipated.
Methods: Three methods including oil in water (O/W), water in oil in water (W/O/W), and solid in oil in
water (S/O/W) emulsion solvent evaporation method were used to optimize the ropivacine loaded PLGA
microspheres. The microspheres were evaluated both in vitro and in rats. The in vitro/in vivo correlation
(IVIVC) were also investigated.
Results: The microspheres prepared by O/W method showed more satisfactory properties and the microspheres
used for evaluation were prepared by O/W method. The particle size, drug loading, encapsulation
efficiency and burst release were 11.19±1.24 μm, 28.37±1.15 %, 98.15±3.98 %, and 10.96±5.37 %
for microspheres with PLGA of 12 kDa, and 6.64±0.61 μm, 19.62±0.89 %, 92.74±4.21 %, and
18.42±5.12 % for microspheres with PLGA of 8 kDa, respectively. These microspheres were also injected
into rats by intravenous, intramuscular and intraperitoneal route, respectively. It was indicated that
the detectable concentration of ropivacine could last for at least 20 days for both kinds of microspheres
in spite of injection routes. The low burst releases at 1 d were also manifested in rats and they were 6.62
%, 6.99 %, 6.48 % for the microspheres with PLGA of 12 kDa, and 4.72 %, 4.33 %, 4.48 % for the microspheres
with PLGA of 8 kDa by intraperitoneal, intramuscular and subcutaneous route, respectively.
A linear relationship between the in vitro release and the in vivo adsorption of ropivacine from microspheres
was also established.
Conclusion: The ropivacine microspheres with sustained release and low burst release were acquired,
which indicated that the postoperative pain relief might last longer and the side effects might get lower.
Therefore, the ropivacine microspheres prepared in this paper have great potential for clinical use.