A novel enteric positioning osmotic pump capsule-based controlled release system of sinomenine hydrochloride: In vitro and in vivo evaluation

Sun, Yang; Zhu, Shuangshuang; Lu, Wenjie; Chen, Jiayi; Sun, Chuan-bin; Guo, Yuxing; Wang, Bin; Gao, Song; Fang, Wenyou; Hu, Rongfeng

doi:10.1016/j.jddst.2018.11.005

Cited by 15 publications

(2 citation statements)

References 30 publications

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“…Multi-dose therapy with SIN-HCl leads to violent fluctuation of blood drug concentration, which may result in serious side effects. Although some sustained release strategies of SIN-HCl have been developed, the marketed SIN-HCl tablets still required administration twice per day, suggesting that novel and long sustained release strategies for SIN are needed. − …”

Section: Introductionmentioning

confidence: 99%

“…We envision a drug combination approach of SIN with SULF or PTM for infection-associated RA therapy. However, the commercial SIN-HCl form exhibits short half-time ( t 1/2 = 1.49 h in rat) and poor pharmacokinetics, , thus requiring frequent administrations to achieve ideal therapeutic effects (20–80 mg once, three times a day) . Multi-dose therapy with SIN-HCl leads to violent fluctuation of blood drug concentration, which may result in serious side effects.…”

Section: Introductionmentioning

confidence: 99%

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Co-amorphous Systems of Sinomenine with Platensimycin or Sulfasalazine: Physical Stability and Excipient-Adjusted Release Behavior

Chen

Zhang

et al. 2022

Mol. Pharmaceutics

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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 Xray 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 g s 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 coamorphous 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 SINaccumulative 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-d 6 , 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 infectionassociated RA.

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