Selek H, Sahin S, Ercan M T, Sargon M, Hincal A A, Kas H S
Faculty of Pharmacy, Hacettepe University, 06100-Ankara, Turkey.
J Microencapsul. 2003 Mar-Apr;20(2):261-71.
Terbutaline sulphate (TBS) is widely used in the treatment of bronchial asthma, chronic bronchitis and emphysema. Because of its short biological half life and dosing schedule, a long acting TBS formulation is required to improve patient compliance. The objective of this study was to develop a TBS containing biodegradable microsphere formulation. Poly(D,L-lactide-co-glycolide) (PLGA) and poly(L-lactic acid) (L-PLA) were chosen as matrix materials. A solvent evaporation method was used for preparation of microspheres. Surface morphology, particle size distribution and encapsulation efficiency were investigated. In vitro release studies were performed in pH 7.4 phosphate buffer. In vitro distribution of microspheres were studied in the Swiss albino male mice. All microspheres were spherical in shape and had a porous surface with mean diameters of 9-21 microm. The encapsulation efficiency was influenced by the polymer type, but not the molecular weight. About 90% of the initial amount was trapped in PLGA microspheres, and the remainder was on the surface. In the case of L-PLA, 50% of the total drug was associated with the surface of microspheres. The In vitro release pattern was biphasic characterized by an initial burst phase followed by a slower phase. The L-PLA microspheres released approximately 92% of the initial payload in 72 h. On the other hand, TBS release was increased with an increase in the molecular weight of PLGA. Biodistribution of L-PLA microspheres was characterized by an initially high uptake (35%) by the lungs. All these results suggest that L-PLA and PLGA microspheres have the potential to be used for passive lung targeting.
硫酸特布他林（TBS）广泛用于治疗支气管哮喘、慢性支气管炎和肺气肿。由于其生物半衰期短且给药方案复杂，需要一种长效TBS制剂来提高患者的依从性。本研究的目的是开发一种含TBS的可生物降解微球制剂。选用聚（D，L-丙交酯-共-乙交酯）（PLGA）和聚（L-乳酸）（L-PLA）作为基质材料。采用溶剂蒸发法制备微球。研究了表面形态、粒径分布和包封率。在pH 7.4的磷酸盐缓冲液中进行体外释放研究。在瑞士白化雄性小鼠中研究了微球的体外分布。所有微球均呈球形，表面多孔，平均直径为9-21微米。包封率受聚合物类型影响，但不受分子量影响。约90%的初始量被困在PLGA微球中，其余在表面。对于L-PLA，50%的总药物与微球表面相关。体外释放模式为双相，其特征是初始突释阶段后是较慢阶段。L-PLA微球在72小时内释放了约92%的初始载药量。另一方面，TBS的释放随着PLGA分子量的增加而增加。L-PLA微球的生物分布特征是肺部最初摄取量较高（35%）。所有这些结果表明，L-PLA和PLGA微球有潜力用于被动肺部靶向。
