Chen Sibao, Singh Jagdish
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, ND 58105, USA.
Int J Pharm. 2005 May 13;295(1-2):183-90. doi: 10.1016/j.ijpharm.2005.02.023.
The objective of this research is to develop injectable polymers solution based controlled release delivery systems for testosterone (TSN), using phase sensitive and thermosensitive polymers. A combination of poly(lactide) (PLA) and solvents mixture of benzyl benzoate (BB) and benzyl alcohol (BA) was used in the phase sensitive polymer delivery system. The effects of solvents system and drug loading on the in vitro TSN release were evaluated. In the case of thermosensitive polymer delivery systems, a series of low-molecular-weight poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers with varying ratio of lactide/glycolide (LA/GA, 2.0-3.5) were studied to control the release of TSN. The effects of varying block length of copolymers 1-4 on the in vitro TSN release were evaluated. Phosphate buffer saline (pH 7.4) containing 0.5% (w/v) Tween-80 was used as in vitro release medium. The amount of the released TSN was determined by an HPLC method. A controlled (zero-order) in vitro release of TSN was observed from both the phase sensitive and thermosensitive polymer delivery systems. Addition of BA (15%, v/v) in solvents system significantly (p<0.05) increased the release rate of TSN (0.33+/-0.01 mg/ml) from phase sensitive delivery system in comparison to solvent without BA (0.27+/-0.00 mg/day). Increasing drug loading also increased release rate. In the case of thermosensitive polymer delivery system, increasing the hydrophobic PLGA block length of copolymers significantly (p<0.05) decreased the release rate of TSN. It is evident from this study that the phase sensitive and thermosensitive polymers are suitable for developing prolong-release injectable implant delivery systems for TSN.
本研究的目的是使用相敏和热敏聚合物开发基于可注射聚合物溶液的睾酮（TSN）控释给药系统。相敏聚合物给药系统中使用了聚丙交酯（PLA）与苯甲酸苄酯（BB）和苯甲醇（BA）的溶剂混合物。评估了溶剂系统和药物负载量对TSN体外释放的影响。在热敏聚合物给药系统中，研究了一系列具有不同丙交酯/乙交酯比例（LA/GA，2.0 - 3.5）的低分子量聚（丙交酯 - 共 - 乙交酯）-聚（乙二醇）-聚（丙交酯 - 共 - 乙交酯）（PLGA - PEG - PLGA）三嵌段共聚物以控制TSN的释放。评估了共聚物1 - 4不同嵌段长度对TSN体外释放的影响。含有0.5%（w/v）吐温80的磷酸盐缓冲盐水（pH 7.4）用作体外释放介质。通过高效液相色谱法测定释放的TSN量。从相敏和热敏聚合物给药系统中均观察到TSN的可控（零级）体外释放。与不含BA的溶剂（0.27±0.00 mg/天）相比，在溶剂系统中添加BA（15%，v/v）显著（p<0.05）提高了TSN从相敏给药系统的释放速率（0.33±0.01 mg/ml）。增加药物负载量也提高了释放速率。在热敏聚合物给药系统中，增加共聚物的疏水PLGA嵌段长度显著（p<0.05）降低了TSN的释放速率。从本研究中可以明显看出，相敏和热敏聚合物适用于开发用于TSN的长效可注射植入给药系统。
