苏尔法萨拉-奎尔塞丁共形系统:持续释放行为和增强的药理动力学
Jia Deng1, Jiangying Li2, Yangwen Peng1
1Clinical Laboratory, Institute of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College & Innovation Centre for Science and Technology, North Sichuan Medical College, Nanchong, Sichuan 637000, PR China.
概括
硫沙拉 (SULF) 和奎尔 (QUE) 的同形系统增强了口服吸收和生物可用性,用于治疗类风湿性关节炎和炎症性肠病. 这些新型配方减少了所需剂量和潜在的副作用.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 材料科学 材料科学 材料科学
背景情况:
- 硫素 (SULF) 的吸收受到排泄物运输体 (MRP2,BCRP) 的限制,因此需要高剂量和频繁的剂量用于类风湿性关节炎 (RA) 和炎症性肠病 (IBD).
- 高剂量的长期治疗SULF增加了不良反应的风险.
研究的目的:
- 开发SULF与Quercetin (QUE) 的共同形态系统 (CAS),以克服口服吸收的限制.
- 描述SULF-QUE CASs的物理特性和溶解行为.
- 评估开发的CASs的体内口服生物利用率和药物动力学概况.
主要方法:
- 使用PXRD,PLM,SEM和mDSC进行系统的表征.
- 通过FTIR和MD模拟进行分子级分析.
- 在动物模型中进行体外溶解研究和体内药理动力学评估.
主要成果:
- SULF-QUE CAS表现出玻璃过渡温度约为113°C和持续释放性质.
- 由于重新结晶的QUE表面结构,与晶体SULF (89.8%) 相比,CAS中的SULF溶解显著减少 (24.5-42.9%).
- 同形态形式显示1.52-2.80倍增强的口服生物可用性和1.84-5.52倍延长的Tmax.
- 这些系统表现出令人满意的物理稳定性.
结论:
- SULF-QUE CASs是改善SULF临床剂量和减少副作用的有希望的策略.
- 这些共同形态系统为RA和IBD提供了潜在的协同治疗方法.
- 开发的配方有效地提高了口服生物可用性,并延长了药物的作用.
相关概念视频
01:05Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
180
Body:Improving a drug's stability in the gastrointestinal (GI) tract is paramount for enhancing its bioavailability and therapeutic effectiveness. Various strategies are employed to protect the drug from the harsh gastric milieu and to ensure its release and absorption at the desired site within the GI tract.Polymer coatings are one such method used to shield drugs from the stomach's acidic environment. By preventing premature drug release, these coatings improve the bioavailability of unstable...
180
01:29Drugs for Treatment of Ulcerative Colitis in IBD
416
Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
416
01:27Bioavailability Enhancement: Drug Permeability Enhancement
174
Body:After oral administration, poor permeability often limits the rate at which drugs are absorbed through the intestinal epithelium. Enhancing drug permeability is crucial for effective therapy, and several strategies have been developed to overcome this challenge.One effective strategy involves the use of lipid-based formulations. These formulations enhance dissolution and solubility, targeting physiological mechanisms to increase drug absorption. This includes stimulating bile salt...
174
01:14Drug Metabolism: Phase II Reactions
4.8K
Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
4.8K
01:24Drugs for Peptic Ulcer Disease: Sucralfate as Mucosal Protective Agents
1.3K
In the intricate landscape of the gastric lumen, excessive acid secretion disrupts the natural defense mechanisms, weakening the mucus-bicarbonate barrier. This vulnerability allows pepsin to infiltrate epithelial cells, digesting mucosal proteins and triggering erosion, leading to ulcer formation.
In this scenario, mucosal protective agents like sucralfate play an essential role. Sucralfate, a complex of sulfated sucrose and aluminum hydroxide, demonstrates its usefulness in acidic conditions,...
In this scenario, mucosal protective agents like sucralfate play an essential role. Sucralfate, a complex of sulfated sucrose and aluminum hydroxide, demonstrates its usefulness in acidic conditions,...
1.3K
01:20Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
477
Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
477