Accelerated stability test of sustained-release thienorphine loaded microspheres for injection
10.16438/j.0513-4870.2022-0289
- VernacularTitle:注射用噻吩诺啡缓释微球加速稳定性研究
- Author:
Xu-dong DAI
1
;
Shan WANG
2
;
Jin-wei DI
2
;
Ming-yuan LI
3
;
Peng YU
3
;
Ai-ping ZHENG
2
;
Jing GAO
2
Author Information
1. College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China; Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China
2. Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China
3. College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China
- Publication Type:Research Article
- Keywords:
thienorphine;
poly(lactic-co-glycolic acid);
microsphere;
accelerated stability test;
critical quality attribute
- From:
Acta Pharmaceutica Sinica
2022;57(8):2503-2511
- CountryChina
- Language:Chinese
-
Abstract:
In order to meet the clinical needs of long-acting sustained-release thienorphine, injectable thienorphine loaded microspheres were developed, and the accelerated stability study was carried out to explore the suitable storage and transportation conditions of the microspheres. Using poly(lactic-co-glycolic acid) (PLGA) as carrier material, 3 batches of microspheres were prepared in pilot scale with emulsion solvent evaporation method. By investigating the in vitro release of thienorphine loaded microspheres at 37, 45, 52, and 60 ℃, and applying the Arrhenius equation, the linear relationship between the release rate constant (lgk) and the temperature (1/T) was established to obtain the equation: lgk = -8.073/T + 24.35 (R2 = 0.985 3), which showed that the release of microspheres at high temperature can be used to predict the release in vitro at 37 ℃, and 52.0 ± 0.5 ℃ was selected as the accelerated release condition in vitro. The quality research methods were established to investigate the changes of critical quality attributes such as microsphere morphology, drug loading, particle size and distribution, polymer molecular weight, and the related substances under accelerated conditions. The difference factor f1 and similarity factor f2 were used to assess the similarity of release behavior under accelerated conditions. The results showed that under the accelerated experimental conditions of 25 ± 2 ℃ and relative humidity (RH) 60% ± 5%, the critical quality attributes of injectable thienorphine loaded microspheres had no significant change in 6 months, suggesting that the long-term storage condition could be 5 ± 3 ℃.
