Pharmaceutical Materials Research Group, Department of Health Science, Luleå University of Technology, Luleå, 971 87, Sweden.
AAPS PharmSciTech. 2013 Mar;14(1):265-76. doi: 10.1208/s12249-012-9883-3. Epub 2013 Jan 8.
The purpose of this work was to characterize theophylline (THF) cocrystals prepared by spray drying in terms of the physicochemical properties and inhalation performance when aerosolized from a dry powder inhaler. Cocrystals of theophylline with urea (THF-URE), saccharin (THF-SAC) and nicotinamide (THF-NIC) were prepared by spray drying. Milled THF and THF-SAC cocrystals were also used for comparison. The physical purity, particle size, particle morphology and surface energy of the materials were determined. The in vitro aerosol performance of the spray-dried cocrystals, drug-alone and a drug-carrier aerosol, was assessed. The spray-dried particles had different size distributions, morphologies and surface energies. The milled samples had higher surface energy than those prepared by spray drying. Good agreement was observed between multi-stage liquid impinger and next-generation impactor in terms of assessing spray-dried THF particles. The fine particle fractions of both formulations were similar for THF, but drug-alone formulations outperformed drug-carrier formulations for the THF cocrystals. The aerosolization performance of different THF cocrystals was within the following rank order as obtained from both drug-alone and drug-carrier formulations: THF-NIC>THF-URE>THF-SAC. It was proposed that micromeritic properties dominate over particle surface energy in terms of determining the aerosol performance of THF cocrystals. Spray drying could be a potential technique for preparing cocrystals with modified physical properties.
本工作旨在通过喷雾干燥制备茶碱（THF）共晶，并从干粉吸入器中雾化时的物理化学性质和吸入性能来表征其特性。通过喷雾干燥制备了茶碱与脲（THF-URE）、糖精（THF-SAC）和烟酰胺（THF-NIC）的共晶。还使用研磨的 THF 和 THF-SAC 共晶进行了比较。测定了材料的物理纯度、粒径、颗粒形态和表面能。评估了喷雾干燥共晶、单独药物和药物载体气溶胶的体外气溶胶性能。喷雾干燥颗粒具有不同的粒径分布、形态和表面能。研磨样品的表面能高于喷雾干燥制备的样品。多阶段液体撞击器和下一代撞击器在评估 THF 喷雾干燥颗粒方面具有良好的一致性。对于 THF，两种制剂的细颗粒分数相似，但对于 THF 共晶，单独药物制剂的性能优于药物载体制剂。从单独药物和药物载体制剂获得的不同 THF 共晶的雾化性能如下：THF-NIC>THF-URE>THF-SAC。据推测，在确定 THF 共晶的气溶胶性能方面，微粉特性比颗粒表面能更为重要。喷雾干燥可能是一种用于制备具有改良物理性质的共晶的潜在技术。
