通过应用酸超溶解原理,降低融挤出温度并增加telmisartan无形固体分散的溶解度和溶解率
Mohammed I Syed1, Hari P Kandagatla1, Abu T M Serajuddin1
1Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
International journal of pharmaceutics
|November 19, 2025
概括
这项研究开发了一种创新的方法,用于制造高点药物如telmisartan的无形固体分散 (ASD). 酸超溶化 (ABS) 方法可以在较低温度下进行热挤出 (HME),从而提高药物的溶解性和溶解性.
科学领域:
- 制药技术 制药技术 制药技术
- 材料科学 材料科学 材料科学
- 药物运输 药物运输 药物运输
背景情况:
- 热挤出 (HME) 是一种无溶剂技术,用于创建无形固体分散 (ASD),改善药物的溶解性和溶解.
- 由于热降解,某些药物的高点 (>200°C) 限制了HME的可行性.
- 泰尔米沙坦是一种水溶性较差,点高 (263°C) 的药物,需要创新的配方策略.
研究的目的:
- 使用热挤出 (HME) 开发泰尔米萨坦的无形固体分散 (ASD).
- 通过酸超溶化 (ABS) 在HME中克服高点药物的局限性.
- 为了提高telmisartan的可溶性和溶解率.
主要方法:
- 用Kollidon® VA 64配制特尔米萨坦无形固体分散剂 (ASDs).
- 使用酸超溶化 (ABS) 与大胺来降低点.
- 使用降温 (120°C) 的热挤出 (HME).
- 使用差分扫描热量计 (DSC) 和粉末X射线衍射 (PXRD) 进行表征.
主要成果:
- 与氨酸的酸相互作用显著增加了telmisartan的水溶性,达到>300 mg/mL.
- 泰尔米萨坦 - 梅格胺混合物的点降至120°C,使得低温HME.
- 含有10%和20%泰尔米沙坦的ASD在120°C时成功挤出.
- DSC和PXRD证实了telmisartan在挤出物中完全无形化.
- 由此产生的ASD与晶体telmisartan相比呈现出明显更快的溶解.
结论:
- 酸超溶化 (ABS) 能够有效地通过热挤出 (HME) 产生无形固体分散 (ASD) 对于像特尔米萨坦这样的高点药物.
- 这种方法显著提高了药物的溶解性和溶解率.
- 开发的ASD可以在120°C的较低,不降解的温度下进行处理.
相关概念视频
01:16Bioavailability Enhancement: Drug Solubility Enhancement
204
Body:Bioavailability is a critical factor in determining a drug's effectiveness. It refers to the proportion of a drug that enters the circulation when introduced into the body and is, as a result, able to have an active effect. Enhancing bioavailability is essential for drugs with poor solubility, as it can significantly impact their therapeutic efficacy. Various methods are employed to increase the solubility of drugs, thereby enhancing their bioavailability.Micronization and nanonization are...
204
01:23Factors Affecting Dissolution: Particle Size and Effective Surface Area
1.6K
Dissolution kinetics, an essential aspect of oral drug delivery, is significantly influenced by the drug's particle size. According to the Noyes-Whitney dissolution model, the dissolution rate correlates directly with the drug's surface area. The larger the surface area, the higher the drug's solubility in water, leading to a faster drug dissolution rate. Reducing particle size increases the effective surface area, enhancing the dissolution process. Micronization and nanosizing are...
1.6K
01:28Factors Influencing Drug Absorption: Pharmaceutical Parameters
383
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
383
01:21Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
648
Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
648
01:27Bioavailability Enhancement: Drug Permeability Enhancement
176
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...
176
01:05Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
185
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...
185