Ma X, Santiago N, Chen Y S, Chaudhary K, Milstein S J, Baughman R A
Pharmaceutical Sciences Laboratory, Emisphere Technologies, Inc., Hawthorne, NY 10532.
J Drug Target. 1994;2(1):9-21. doi: 10.3109/10611869409015889.
Drug-loaded proteinoid microspheres were freeze-dried to facilitate shipping and handling and to enable long term storage. Heparin was chosen as the model drug in developing the optimum lyophilization process. The factors influencing the integrity of either heparin-loaded or unloaded ('empty') proteinoid microspheres during freeze-drying were determined, with emphasis on: selecting an optimum freezing and resuspending temperature; choosing an appropriate cryoprotectant and its optimum concentration in the formulation; and, designing a suitable method for formulating the microspheres. Freezing at/below -70 degrees C was found to minimize damage to the microspheres. Addition of sugars, such as trehalose and lactose, as cryoprotectants, further increased the stability of the heparin-loaded microspheres during freeze-drying. The optimum trehalose or lactose concentrations were determined to be 5% (w/v). Using the optimumized lyophilization process described in this manuscript, microspheres remained intact during freeze-drying. The freeze-dried microspheres were stable for at least three months post-lyophilization.
载药类蛋白微球经过冷冻干燥，以方便运输和处理，并实现长期储存。在开发最佳冻干工艺时，选择肝素作为模型药物。确定了冻干过程中影响载肝素或未载药（“空”）类蛋白微球完整性的因素，重点包括：选择最佳冷冻和重悬温度；选择合适的冷冻保护剂及其在制剂中的最佳浓度；以及设计一种合适的微球制备方法。发现冷冻至/低于-70摄氏度可将对微球的损害降至最低。添加糖类，如海藻糖和乳糖，作为冷冻保护剂，进一步提高了载肝素微球在冻干过程中的稳定性。确定海藻糖或乳糖的最佳浓度为5%（w/v）。使用本文所述的优化冻干工艺，微球在冻干过程中保持完整。冻干后的微球在冻干后至少三个月内保持稳定。
