Chen Jie, Ormes James D, Higgins John D, Taylor Lynne S
Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University , West Lafayette, Indiana 47907, United States.
Mol Pharm. 2015 Feb 2;12(2):533-41. doi: 10.1021/mp5006245. Epub 2015 Jan 22.
Amorphous solid dispersions are frequently prepared by spray drying. It is important that the resultant spray dried particles do not crystallize during formulation, storage, and upon administration. The goal of the current study was to evaluate the impact of surfactants on the crystallization of celecoxib amorphous solid dispersions (ASD), suspended in aqueous media. Solid dispersions of celecoxib with hydroxypropylmethylcellulose acetate succinate were manufactured by spray drying, and aqueous suspensions were prepared by adding the particles to acidified media containing various surfactants. Nucleation induction times were evaluated for celecoxib in the presence and absence of surfactants. The impact of the surfactants on drug and polymer leaching from the solid dispersion particles was also evaluated. Sodium dodecyl sulfate and Polysorbate 80 were found to promote crystallization from the ASD suspensions, while other surfactants including sodium taurocholate and Triton X100 were found to inhibit crystallization. The promotion or inhibition of crystallization was found to be related to the impact of the surfactant on the nucleation behavior of celecoxib, as well as the tendency to promote leaching of the drug from the ASD particle into the suspending medium. It was concluded that surfactant choice is critical to avoid failure of amorphous solid dispersions through crystallization of the drug.
无定形固体分散体通常通过喷雾干燥制备。重要的是，所得喷雾干燥颗粒在制剂、储存和给药过程中不会结晶。本研究的目的是评估表面活性剂对悬浮在水性介质中的塞来昔布无定形固体分散体（ASD）结晶的影响。通过喷雾干燥制备塞来昔布与醋酸羟丙甲纤维素琥珀酸酯的固体分散体，并通过将颗粒加入含有各种表面活性剂的酸化介质中来制备水性悬浮液。评估了在有和没有表面活性剂的情况下塞来昔布的成核诱导时间。还评估了表面活性剂对固体分散体颗粒中药物和聚合物浸出的影响。发现十二烷基硫酸钠和聚山梨酯80可促进ASD悬浮液中的结晶，而其他表面活性剂，包括牛磺胆酸钠和曲拉通X100，则可抑制结晶。发现结晶的促进或抑制与表面活性剂对塞来昔布成核行为的影响以及促进药物从ASD颗粒浸出到悬浮介质中的趋势有关。得出的结论是，表面活性剂的选择对于避免无定形固体分散体因药物结晶而失效至关重要。
