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

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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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Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
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When a drug is taken orally, it undergoes a journey starting from the gastrointestinal (GI) tract, passing through the portal vein, reaching the liver, and finally entering the systemic circulation. This process involves the absorption of the drug across the GI tract. The liver is the primary site for metabolizing the drug, with some metabolism also occurring in the gut wall. This journey significantly reduces the quantity of the drug that reaches the systemic circulation, a phenomenon known as...
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Pharmaceutical equivalents, by definition, are drug products with the same active ingredient in the same quantities, encapsulated in identical dosage forms, and intended for the same administration routes. These pharmaceutical equivalents are deemed bioequivalent if the bioavailability of the active entity in the drug preparations is similar. Moreover, pharmaceutical equivalents demonstrating bioequivalence are also regarded as therapeutically equivalent. This means that when used as directed,...
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Factors Influencing Drug Absorption: Physicochemical Parameters01:22

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The physicochemical characteristics of drugs play a crucial role in formulating stable and bioavailable drug products. The solubility of a drug, governed by the varying pH along the GI tract and its dissociation constant (pKa), is pivotal in determining its ionization state and absorption rate. Notably, weak acids and bases remain unionized and are absorbed more rapidly.
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Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
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A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
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具有提高溶解度和生物可用性的晶.

Bingqing Zhu1, Zhenfeng Ding1, Xiaoyi Rong1

  • 1Pharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.

Pharmaceuticals (Basel, Switzerland)
|January 25, 2025
PubMed
概括

研究人员开发了一种新型的Silybin-L-proline共晶体,以克服乳提取物西利马林的溶解性差和生物可用性低. 这种新形式显著增强了西利宾.

关键词:
对于L-proline来说,这是一个很好的方法.生物可用性 生物可用性协同晶体 协同晶体 是一个这里是西里宾 (silybin).溶解度 溶解度 溶解度 溶解度

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科学领域:

  • 药理学 药理学 是一个学科.
  • 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:

  • 西利玛林,来自乳,显示治疗承诺肝脏疾病.
  • 它的主要活性成分Silybin的临床应用受到溶解性差和生物可用性低的阻碍.
  • 需要新的配方策略来增强Silybin的治疗潜力.

研究的目的:

  • 开发和描述一种新型的Silybin共晶,以改善其物理化学特性.
  • 为了评估Silybin-L-proline联合晶体的溶解,超和药理动力学特征.
  • 评估共晶配方在增强西利宾输送方面的潜力.

主要方法:

  • 合成西利宾-L-烯共晶.
  • 使用PXRD,TGA,DSC和FTIR进行物理化学表征.
  • 在各种pH条件下使用沉抑制剂进行体外溶解研究.
  • 在老鼠模型中的体内药理动力学评估.

主要成果:

  • 西利宾-L-合晶体显著改善了溶解,特别是在酸性介质中.
  • 沉抑制剂,如PVP,有效地延长了超和.
  • 晶在老鼠中实现了16倍的生物可用性增加,超过了商业配方.

结论:

  • 氨酸-L-氨酸共晶体代表了一种有前途的方法来增强氨酸的溶解和生物可用性.
  • 这种配方策略有可能提高西利马林在肝病治疗中的临床疗效.
  • 进一步开发可能会导致更有效的基于Silybin的治疗方法.