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Factors Influencing Drug Absorption: Pharmaceutical Parameters01:28

Factors Influencing Drug Absorption: Pharmaceutical Parameters

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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...
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Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism01:21

Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism

673
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...
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Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry01:20

Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

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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...
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Factors Affecting Dissolution: Particle Size and Effective Surface Area01:23

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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...
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In Vitro Drug Dissolution: Alternative Methods01:17

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Alternative drug dissolution methods include the rotating bottle, intrinsic dissolution test, peristalsis, and the Franz diffusion cell method. The rotating bottle method involves meticulously rotating tightly capped controlled-release beads in a temperature-controlled bath. Periodic decanting of samples allows for residue assay, followed by refilling with fresh medium and testing at various pH levels to emulate the gastrointestinal tract conditions.In contrast, the intrinsic dissolution test...
198
Bioavailability Enhancement: Drug Solubility Enhancement01:16

Bioavailability Enhancement: Drug Solubility Enhancement

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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...
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Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
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开发多组件固体配方策略,以提高 PROTAC 解体效果.

Martin A Screen1, Sean Askin2, James F McCabe3

  • 1Department of Chemistry, Durham University, South Road, Durham DH1 3LE, U.K.

Molecular pharmaceutics
|October 2, 2025
PubMed
概括
此摘要是机器生成的。

无形固体分散 (ASDs) 增强了解向金马 (PROTACs) 的生物可用性,使其能够通过口服药物输送. 与其他配方相比,用泥制备的ASD显示出优越的可溶性增强和稳定性.

关键词:
在ASD中,使用的是ASD.这就是 PROTACs.没有形状的无形.溶解溶解是一种这是一种配方配方.

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科学领域:

  • 制药科学 制药科学
  • 药物运输 药物运输 药物运输
  • 药用化学 医学化学

背景情况:

  • 蛋白质溶解向金马 (PROTACs) 是癌症的新疗法,但它们的溶解性差和无形性限制了生物利用性.
  • 开发PROTACs的口服配方是具有挑战性的,因为它们的物理化学特性和有限的样本可用性.

研究的目的:

  • 用基甲基纤维素酸 (HPMCAS) 来研究无形固体分散 (ASDs),以增强 PROTACs 的溶解和生物可用性.
  • 为了比较配方策略,包括泥转化与溶剂蒸发,并评估物理稳定性.

主要方法:

  • 用HPMCAS准备四个大脑招募的PROTAC (AZ1-4) 的ASD.
  • 自闭症的特征,包括药物负载,超和,物理稳定性 (Tg,DSC,FTIR) 和溶解测试.
  • 与同形配方和纯无形活性药物成分 (API) 的比较.

主要成果:

  • 与纯无形API相比,AZ1的ASD显示药物超和的增加高达2倍.
  • 用泥制备的ASD显示出更大的可溶性增强,并且在较高的药物负载下保持优势,而不是溶剂蒸发的ASD.
  • 在加速条件下,ASDs表现出良好的物理稳定性,与缺乏溶解益处的同形配方不同.

结论:

  • 自闭症是一种可行的策略,可以提高PROTAC的口服生物可用性,并创建可商业化的固体形式.
  • 通过泥转换的配方优于溶剂蒸发来提高PROTAC的溶解性.
  • 需要进行进一步的研究,以优化PROTACs等超出5规则 (bRo5) 化合物的配方方法.