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

Factors Affecting Dissolution: Particle Size and Effective Surface Area

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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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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 Influencing Bioavailability: First-Pass Elimination01:23

Factors Influencing Bioavailability: First-Pass Elimination

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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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Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH01:21

Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH

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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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Factors Influencing Drug Absorption: Presystemic Elimination01:24

Factors Influencing Drug Absorption: Presystemic Elimination

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The pharmacokinetic journey of oral drugs begins with a crucial first pass through the hepatic portal system, called the first-pass effect. This first pass significantly impacts bioavailability — the proportion of a drug that enters systemic circulation and is available for therapeutic action. The primary route sees the drug absorbed by intestinal membranes and then shunted to the liver via the hepatic portal vein. Here, pre-systemic elimination occurs as drugs face metabolism or biliary...
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Factors Influencing Drug Absorption: Physicochemical Parameters01:22

Factors Influencing Drug Absorption: Physicochemical Parameters

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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.
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
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脂质纳米颗粒用于增强口服生物利用性.

Anushareddy Gangavarapu1, Lillian V Tapia-Lopez2, Barnali Sarkar2

  • 1Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, MS 38677, USA. bsnabi@olemiss.edu.

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概括

脂质纳米颗粒 (LNP) 增强口服药物输送,使药物吸收不良. 这些多功能系统通过克服胃肠道挑战和利用淋巴管道来提高生物可用性.

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科学领域:

  • 制药科学 制药科学
  • 纳米技术 纳米技术
  • 药物输送系统 药物输送系统

背景情况:

  • 脂质纳米颗粒 (LNP) 正在成为生物制药分类系统 (BCS) 第二类和第四类药物的有希望的药物递送系统.
  • 这些药物通常由于降解和低透性而表现出不良的口服吸收和生物可用性.
  • 包括固体脂质纳米粒子 (SLN) 和纳米结构脂质载体 (NLC) 在内的LNP通过封装各种类型的药物来提供解决方案.

研究的目的:

  • 提供关于脂质纳米颗粒 (LNPs) 的最新信息,以增强口服药物透性差的生物可用性.
  • 突出LNP通过哪些机制来改善跨胃肠道屏障的药物吸收.
  • 讨论目前的挑战和基于LNP的口服药物输送的未来方向.

主要方法:

  • 关于脂质纳米粒子配方及其在口服药物输送中的应用的最新文献的综述.
  • 分析LNP机制,包括胃肠道过境,跨膜吸收和运输动力学.
  • 在LNP设计和评估中使用的计算工具的探索.

主要成果:

  • 脂质纳米粒子在增加BCSII和IV类药物的生物可用性方面具有显著的潜力.
  • 临床药物利用独特的脂质特性 (生物降解性,生物相容性) 和运输途径来增强药物吸收.
  • 选择性淋巴运输通路有助于通过LNP改善药物的生物可用性.

结论:

  • 脂质纳米颗粒为改善具有挑战性的化合物的口服药物输送提供了一个多功能平台.
  • 了解跨胃肠道障碍的LNP机制对于优化药物输送至关重要.
  • 对LNP障碍和未来前景的进一步研究对于推进口服药物递送系统至关重要.