Xin Chen

Natural products are the main source of drug development and nutritional supplements due to their abundant bioactivity and guaranteed safety. Nonetheless, their journey from the laboratory to market faces formidable hurdles, primarily stemming from issues such as poor solubility and limited bioavailability. To combat these hurdles, coamorphous (CAM) technology has emerged as a recent solution, offering advantages in solubility enhancement, stability, drug loading capacity, and combination with other drugs. Coamorphization of natural active pharmaceutical ingredients (APIs) holds promise for enhancing their druggability and presents an opportunity for combining them with synthetic drugs. This review encapsulates recent advancements in natural API CAM systems, covering their preparation and characterization techniques and diverse applications, summarizing reported systems, and offering an outlook on future possibilities and perspectives.

Vitamin B2 (VB2), a functional ingredient found in various foods and herbal medicines, is crucial for metabolic processes, with its deficiency linked to inflammatory diseases. However, the poor water solubility of VB2 hampers its development and application. This study employed chlorogenic acid (CGA) to create a coamorphous system with VB2 to improve its physicochemical properties. The coamorphous VB2-CGA was initially confirmed using powder X-ray diffraction (PXRD) and modulated temperature differential scanning calorimetry (mDSC). Fourier-transform infrared spectroscopy (FTIR) and molecular dynamics (MD) simulations revealed potential molecular interactions within the system. The water solubility and physical stability of the VB2-CGA coamorphous system were further evaluated. Notably, the VB2-CGA system exhibited a 2.7-fold solubility increase compared to crystalline VB2 and maintained physical stability for at least one year under dry conditions. Additionally, the potential multitarget synergistic anti-inflammatory effects of the VB2-CGA coamorphous system were also disclosed using network pharmacological analysis.

Sinomenine (SIN) is a benzyltetrahydroisoquinoline-type alkaloid isolated from the dried plant root and stem of Sinomenium acutum (Thumb.) Rehd.et Wils, which shows potent anti-inflammatory and analgesic effects. As a transforming disease-modifying anti-rheumatic drug, SIN has been used to treat rheumatoid arthritis over twenty-five years in China. In recent years, SIN is also in development for use against other disorders, including colitis, pain, traumatic brain injury, and uveitis. However, its commercial hydrochloride (SIN-HCl) shows low oral bioavailability and certain allergic reactions in patients, due to the release of histamine. Therefore, a large number of pharmaceutical strategies have been explored to address these liabilities, such as prolonging release behaviors, enhancing skin permeation and adsorption for transdermal delivery, targeted SIN delivery using new material or conjugates, and co-amorphous technology. This review discusses these different delivery strategies and approaches employed to overcome the limitations of SIN for its efficient delivery, in order to achieve improved bioavailability and reduced side effects. The potential advantages and limitations of SIN delivery strategies are elaborated along with discussions of potential future SIN drug development strategies.

There is strong interest to develop affordable treatments for the infection-associated rheumatoid arthritis (RA). Here, we present a drug-drug co-amorphous strategy against RA and the associated bacterial infection by the preparation and characterization of two co-amorphous systems of sinomenine (SIN) with platensimycin (PTM) or sulfasalazine (SULF), two potent antibiotics. Both of them were comprehensively characterized using powder X-ray diffraction, temperature-modulated differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The co-amorphous forms of SIN-PTM and SIN-SULF exhibited high T_gs at 139.10 ± 1.0 and 153.3 ± 0.2 °C, respectively. After 6 months of accelerated tests and 1 month of drug-excipient compatibility experiments, two co-amorphous systems displayed satisfactory physical stability. The formation of salt and strong intermolecular interactions between SIN and PTM or SULF, as well as the decreased molecular mobility in co-amorphous systems, may be the intrinsic mechanisms underlying the excellent physical stability of both co-amorphous systems. In dissolution tests, two co-amorphous systems displayed distinct reduced SIN-accumulative releases (below 20% after 6 h of release experiments), which may lead to its poor therapeutic effect. Hence, we demonstrated a controlled release strategy for SIN by the addition of a small percentage of polymers and a small-molecule surfactant to these two co-amorphous samples as convenient drug excipients, which may also be used to improve the unsatisfactory dissolution behaviors of the previously reported SIN co-amorphous systems. Several hydrogen bonding interactions between SIN and PTM or SULF could be identified in NMR experiments in DMSO-d₆, which may be underlying reasons of decreased dissolution behaviors of both co-amorphous forms. These drug-drug co-amorphous systems could be a potential strategy for the treatment of infection-associated RA.