Accelerated in vitro release testing method for naltrexone loaded PLGA microspheres

作者：Andhariya, Janki V.; Choi, Stephanie; Wang, Yan; Zou, Yuan; Burgess, Diane J.; Shen, Jie^*

来源：International Journal of Pharmaceutics, 2017, 520(1-2): 79-85.

DOI：10.1016/j.ijpharm.2017.01.050

• PLGA microspheres
• Naltrexone
• Compositionally equivalent
• USP apparatus 4
• Accelerated in vitro release testing

The objective of the present study was to develop a discriminatory and reproducible accelerated release testing method for naltrexone loaded parenteral polymeric microspheres. The commercially available naltrexone microsphere product (Vivitrol) was used as the testing formulation in the in vitro release method development, and both sample-and-separate and USP apparatus 4 methods were investigated. Following an in vitro drug stability study, frequent media replacement and addition of anti-oxidant in the release medium were used to prevent degradation of naltrexone during release testing at "real-time" (37 degrees C) and "accelerated" (45 degrees C), respectively. The USP apparatus 4 method was more reproducible than the sample-and-separate method. In addition, the accelerated release profile obtained using USP apparatus 4 had a shortened release duration (within seven days), and good correlation with the "realtime" release profile. Lastly, the discriminatory ability of the developed accelerated release method was assessed using compositionally equivalent naltrexone microspheres with different release characteristics. The developed accelerated USP apparatus 4 release method was able to detect differences in the release characteristics of the prepared naltrexone microspheres. Moreover, a linear correlation was observed between the "real-time" and accelerated release profiles of all the formulations investigated, suggesting that the release mechanism(s) may be similar under both conditions. These results indicate that the developed accelerated USP apparatus 4 method has the potential to be an appropriate fast quality control tool for long-acting naltrexone PLGA microspheres.

• 出版日期2017-3-30