Salem Ala', Takácsi-Nagy Anna, Nagy Sándor, Hagymási Alexandra, Gősi Fruzsina, Vörös-Horváth Barbara, Balić Tomislav, Pál Szilárd, Széchenyi Aleksandar
Institute of Pharmaceutical Technology and Biopharmacy, University of Pécs, 7622 Pécs, Hungary.
Department of Chemistry, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
Pharmaceutics. 2021 Feb 19;13(2):277. doi: 10.3390/pharmaceutics13020277.
Drug-drug cocrystals are formulated to produce combined medication, not just to modulate active pharmaceutical ingredient (API) properties. Nano-crystals adjust the pharmacokinetic properties and enhance the dissolution of APIs. Nano-cocrystals seem to enhance API properties by combining the benefits of both technologies. Despite the promising opportunities of nano-sized cocrystals, the research at the interface of nano-technology and cocrystals has, however, been described to be in its infancy. In this study, high-pressure homogenization (HPH) and high-power ultrasound were used to prepare nano-sized cocrystals of 4-aminosalysilic acid and sulfamethazine in order to establish differences between the two methods in terms of cocrystal size, morphology, polymorphic form, and dissolution rate enhancement. It was found that both methods resulted in the formation of form I cocrystals with a high degree of crystallinity. HPH yielded nano-sized cocrystals, while those prepared by high-power ultrasound were in the micro-size range. Furthermore, HPH produced smaller-size cocrystals with a narrow size distribution when a higher pressure was used. Cocrystals appeared to be needle-like when prepared by HPH compared to those prepared by high-power ultrasound, which had a different morphology. The highest dissolution enhancement was observed in cocrystals prepared by HPH; however, both micro- and nano-sized cocrystals enhanced the dissolution of sulfamethazine.
药物-药物共晶体的配方旨在生产联合药物，而不仅仅是调节活性药物成分（API）的性质。纳米晶体可调节药代动力学性质并增强API的溶解。纳米共晶体似乎通过结合两种技术的优点来增强API的性质。尽管纳米尺寸共晶体有广阔前景，但纳米技术与共晶体界面的研究仍处于起步阶段。在本研究中，采用高压均质法（HPH）和高功率超声来制备对氨基水杨酸和磺胺二甲嘧啶的纳米尺寸共晶体，以便在共晶体尺寸、形态、多晶型和溶解速率增强方面确定这两种方法之间的差异。结果发现，两种方法均导致形成具有高度结晶度的I型共晶体。HPH法得到纳米尺寸的共晶体，而高功率超声法制备的共晶体处于微米尺寸范围。此外，当使用较高压力时，HPH法产生尺寸更小、尺寸分布更窄的共晶体。与高功率超声法制备的具有不同形态的共晶体相比，HPH法制备的共晶体呈针状。在HPH法制备的共晶体中观察到最高的溶解增强效果；然而，微米和纳米尺寸的共晶体均增强了磺胺二甲嘧啶的溶解。
