University of Bonn, Institute of Pharmacy, Laboratory of Pharmaceutical Technology and Biopharmaceutics, Bonn, Germany.
University of Bonn, Institute of Pharmacy, Laboratory of Pharmaceutical Technology and Biopharmaceutics, Bonn, Germany; University of New Mexico, College of Pharmacy, Albuquerque, NM, USA.
Int J Pharm. 2020 Nov 30;590:119932. doi: 10.1016/j.ijpharm.2020.119932. Epub 2020 Oct 1.
Rifampicin is an antibiotic used in tuberculosis therapy showing extensive (solvato-) polymorphism. Per oral administration of high doses is recommended, but application as dry powder for inhalation at the site of infection being the lungs, is desirable. Recrystallization from ethanol and consecutive spray drying is reported to yield a rifampicin dihydrate with suitable aerosol performance and stability. Nevertheless, the origin of water in the crystal remained unclear and demanded further investigation so to clarify its solid state throughout manufacture and storage. The present study reports the relationship of (solvato-) polymorphs occurring during manufacture and storage of samples recrystallized and spray dried from ethanol, methanol and water and it was concluded that processes involving a recrystallization from EtOH and MeOH produce particles of a common isostructural group of channel solvates. Samples recrystallized and spray dried from water were identified as members of another isostructural group, which was already characterized in literature. As a second aim, aerosol performance and storage stability of the formulations were investigated and all samples showed stable aerosol performance. Chemical stability of samples spray dried from ethanol was found suitable over a period of six months, whereas samples spray dried from methanol or water showed significant degradation.
利福平是一种用于结核病治疗的抗生素，具有广泛的（溶剂）多态性。推荐口服大剂量，但理想情况下是将其作为干粉吸入到感染部位肺部。据报道，从乙醇中重结晶并连续喷雾干燥可得到具有适当气溶胶性能和稳定性的利福平二水合物。然而，晶体中水分的来源仍不清楚，需要进一步研究以阐明其在整个制造和储存过程中的固体状态。本研究报告了在乙醇、甲醇和水中重结晶和喷雾干燥的样品在制造和储存过程中发生的（溶剂）多态性之间的关系，并得出结论，涉及从 EtOH 和 MeOH 重结晶的过程会产生具有共同结构的通道溶剂化物的颗粒组。从水中重结晶和喷雾干燥的样品被鉴定为另一个结构组的成员，该结构组已在文献中进行了表征。作为第二个目标，研究了制剂的气溶胶性能和储存稳定性，所有样品均表现出稳定的气溶胶性能。从乙醇喷雾干燥的样品的化学稳定性在六个月的时间内是合适的，而从甲醇或水喷雾干燥的样品则显示出明显的降解。
