Accelerated in vitro release testing method for naltrexone loaded PLGA microspheres.
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°C) and "accelerated" (45°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 "real-time" 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.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, CT, 06269, USA.
Janki V
JV
Andhariya
Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, 20993, USA.
Stephanie
S
Choi
Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, 20993, USA.
Yan
Y
Wang
Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, 20993, USA.
Yuan
Y
Zou
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, CT, 06269, USA.
Diane J
DJ
Burgess
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, CT, 06269, USA. Electronic address: jie.shen@uconn.edu.
Jie
J
Shen
D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D004355:Drug Stability; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D009271:Naltrexone / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015203:Reproducibility of Results; D013696:Temperature; D013997:Time Factors
D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D009271:Naltrexone
Accelerated in vitro release testing; Compositionally equivalent; Naltrexone; PLGA microspheres; USP apparatus 4