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Development and Evaluation of Ropivacaine Loaded Poly(Lactic-Co- Glycolic Acid) Microspheres with Low Burst Release

Author(s):

Xiqing Zhao, Yue Gao, Xuemei Tang, Wei Lei, Yang Yang, Fanglin Yu, Yan Liu, Meiyan Yang, Yuli Wang, Wei Gong, Zhiping Li*, Chun Sheng Gao* and Xingguo Mei   Pages 1 - 9 ( 9 )

Abstract:


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.

Keywords:

Microspheres, In vitro release, Pharmacokinetic, Sustained release effect, Initial burst release, IVIVC

Affiliation:

Insititute of Pharmacology and Toxicology, Academy of Military Medicine Sciences, Beijing 100850, Insititute of Pharmacology and Toxicology, Academy of Military Medicine Sciences, Beijing 100850, Insititute of Pharmacology and Toxicology, Academy of Military Medicine Sciences, Beijing 100850, Insititute of Pharmacology and Toxicology, Academy of Military Medicine Sciences, Beijing 100850, Insititute of Pharmacology and Toxicology, Academy of Military Medicine Sciences, Beijing 100850, Insititute of Pharmacology and Toxicology, Academy of Military Medicine Sciences, Beijing 100850, Insititute of Pharmacology and Toxicology, Academy of Military Medicine Sciences, Beijing 100850, Insititute of Pharmacology and Toxicology, Academy of Military Medicine Sciences, Beijing 100850, Insititute of Pharmacology and Toxicology, Academy of Military Medicine Sciences, Beijing 100850, Insititute of Pharmacology and Toxicology, Academy of Military Medicine Sciences, Beijing 100850, Insititute of Pharmacology and Toxicology, Academy of Military Medicine Sciences, Beijing 100850, Insititute of Pharmacology and Toxicology, Academy of Military Medicine Sciences, Beijing 100850, Insititute of Pharmacology and Toxicology, Academy of Military Medicine Sciences, Beijing 100850



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