Università degli Studi di Milano, Dipartimento di Scienze Farmaceutiche, Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", via G. Colombo 71 20133, Milan, Italy.
Università degli Studi di Milano, Dipartimento di Scienze Farmaceutiche, Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", via G. Colombo 71 20133, Milan, Italy.
Int J Pharm. 2024 Dec 5;666:124836. doi: 10.1016/j.ijpharm.2024.124836. Epub 2024 Oct 13.
The present study focused on the use of milk as a novel excipient for the manufacture of pharmaceutical dosage forms specifically designed for the pediatric population. Dairy milks with different fat contents were studied to deliver paracetamol orally. The World Health Organization included milk in the list of GRAS (generally recognized as safe) substances, which together with its taste-masking ability and solubility solving properties, makes it a good candidate as an excipient in formulations containing paracetamol for pediatrics. The influence of the fat content in the milk, the fraction of paracetamol, the type of diluent and drying temperature (considered independent variables) were systematically investigated using a Design of Experiments (DoE) approach for the preparation of granules for oral administration, by wet agglomeration using different processing techniques, enabled the construction of mathematical models reflecting the correlation between the variables. Four different techniques were evaluated: wet granulation by low shear mixer, wet granulation by high shear mixer, wet granulation by fluidized bed, and extrusion and spheronization. The granules and pellets obtained were characterized for size, and size distribution of agglomerates, and complete release of the drug (dependent variables), according to the European Pharmacopoeia. The fraction of fat content in the milk promoted an increase on the dissolution rate of paracetamol. The key finding of the first two process techniques was a migration of paracetamol from powdered agglomerates towards the larger particles, probably due to friction and attrition events, which created a fraction of smaller size granules due to the fragmentation and loss of powder from the larger granules. The study has confirmed the potential of milk to be a novel and efficient excipient that can be used as a liquid binder in various agglomeration techniques to deliver drugs orally.
本研究专注于将牛奶作为一种新颖的赋形剂用于制造特定为儿科人群设计的药物剂型。研究了不同脂肪含量的牛奶，以口服递送扑热息痛。世界卫生组织将牛奶列入 GRAS（一般认为安全）物质清单中，其掩味能力和溶解度解决性能使其成为含有扑热息痛的儿科配方中的赋形剂的良好候选物。使用实验设计（DoE）方法系统地研究了牛奶中的脂肪含量、扑热息痛的分数、稀释剂的类型和干燥温度（视为独立变量）对通过湿法造粒制备口服颗粒的影响，使用不同的加工技术进行湿法造粒，构建了反映变量之间相关性的数学模型。评估了四种不同的技术：低剪切混合器湿法造粒、高剪切混合器湿法造粒、流化床湿法造粒和挤出和滚圆。根据欧洲药典，对获得的颗粒和丸剂进行粒径和团聚体粒径分布以及药物完全释放（因变量）的特性进行了表征。牛奶中的脂肪含量分数促进了扑热息痛的溶解速率的提高。前两种工艺技术的关键发现是扑热息痛从粉末团聚体向较大颗粒的迁移，可能是由于摩擦和磨损事件导致的，这些事件导致较小粒径的颗粒的形成，因为较大颗粒的粉末碎裂和损失。该研究证实了牛奶作为一种新颖且有效的赋形剂的潜力，可作为各种团聚技术中的液体粘合剂用于口服递送药物。
