Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, New York, 11439, USA.
, Ashland Specialty Ingredients, 500 Hercules Rd, Wilmington, USA.
AAPS PharmSciTech. 2021 May 13;22(4):154. doi: 10.1208/s12249-021-02018-6.
In twin screw melt granulation, granules are produced by passing mixtures of drug substances and polymeric binders through twin screw extruder such that temperatures are maintained below melting point of drugs but above glass transition of polymers used, whereby the polymers coat surfaces of drug particles and cause their agglomeration into granules. Since various formulation factors, such as binder type and concentration, and processing variables like extrusion temperature, screw configuration, and screw speed, can influence the granulation process, the present investigation was undertaken to study their effects on tabletability of granules produced. Three different types of polymeric binders, Klucel® EXF (hydroxypropyl cellulose), Eudragit® EPO (polyacrylate binder), and Soluplus® (polyvinyl caprolactam-co-vinyl acetate-ethylene glycol graft polymer), were used at 2, 5, and 10% concentrations. Metformin hydrochloride (HCl) (mp: 222°C) and acetaminophen (mp: 169°C) were used as model drugs, and drug-polymer mixtures with metformin HCl were extruded at 180, 160, and 130°C, while those with acetaminophen were extruded at 130 and 110°C. Other process variables included screw configurations: low, medium, and high shear for metformin HCl, and low and medium shear for acetaminophen; feed rates: 20 and 60 g/min; and screw speed of 100 and 300 RPM. Formulation and process variables had significant impact on tabletability. The target tensile strength of ≥2 MPa could be obtained with all polymers and at all processing temperatures when metformin HCl was granulated at 180°C and acetaminophen at 130°C. At other temperatures, the target tensile strength could be achieved at certain specific sets of processing conditions.
在双螺杆熔融造粒中，通过双螺杆挤出机将药物物质和聚合物粘合剂的混合物通过，从而使温度保持在药物熔点以下但高于所用聚合物的玻璃化转变温度，从而使聚合物涂覆药物颗粒的表面并导致它们团聚成颗粒。由于各种制剂因素，如粘合剂类型和浓度，以及加工变量，如挤出温度、螺杆构型和螺杆速度，可以影响造粒过程，因此进行了本研究以研究它们对所生产颗粒可压性的影响。使用了三种不同类型的聚合物粘合剂，Klucel® EXF（羟丙基纤维素）、Eudragit® EPO（聚丙烯酸粘合剂）和 Soluplus®（聚维酮己内酯-co-醋酸乙烯酯-乙二醇接枝聚合物），浓度分别为 2%、5%和 10%。使用盐酸二甲双胍（mp：222°C）和对乙酰氨基酚（mp：169°C）作为模型药物，将盐酸二甲双胍与药物-聚合物混合物在 180、160 和 130°C 下挤出，而对乙酰氨基酚则在 130 和 110°C 下挤出。其他加工变量包括螺杆构型：低、中、高剪切力用于盐酸二甲双胍，低和中剪切力用于对乙酰氨基酚；进料速率：20 和 60 g/min；螺杆速度为 100 和 300 RPM。制剂和加工变量对可压性有显著影响。当用 180°C 挤出盐酸二甲双胍和 130°C 挤出对乙酰氨基酚时，所有聚合物和所有加工温度都可以获得目标拉伸强度≥2 MPa。在其他温度下，可以在某些特定的加工条件下达到目标拉伸强度。
