相关实验视频

Updated: Jun 5, 2025

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

基于生理学的生物制药建模与生物预测溶解相结合,用于开发美沙胺肠膜涂层片的生物等效配方:一个难以破解的坚硬坚果

Sivacharan Kollipara¹, Pankaj Kumar Prabhat², Paramita Saha³

¹Biopharmaceutics Group, Global Clinical Management, Dr. Reddy's Laboratories Ltd., Integrated Product Development Organization (IPDO), Bachupally, Medchal Malkajgiri District, Hyderabad, 500090, Telangana, India. sivacharankollipara@drreddys.com.

AAPS PharmSciTech

|December 3, 2024

概括

开发一种生物预测模型,用于预测体内养行为. 帮助预测体内养行为. 这种方法解决了性结肠炎治疗方法实现生物等价性的挑战.

科学领域:

药物动力学和生物制药学
药物配方和输送方法药物配方和输送方法
胃肠病学治疗方法治疗方法

背景情况:

梅沙胺是性结肠炎的关键抗炎剂,但其配方存在生物等价性 (BE) 挑战.
在体内变异性和复杂的养状态使生物等价梅沙胺配方的开发复杂化.
准确预测肠涂层梅沙的体内性能对于治疗疗效至关重要.

研究的目的:

开发一种新的生物预测溶解介质,用于梅沙胺肠膜涂层片.
将这种介质整合到基于生理学的生物制药模型 (PBBM) 中,用于预测体内养行为.
评估模型在虚拟生物等价性 (VBE) 研究和潜在的BE预测中的实用性.

主要方法:

开发USP III梯度介质,模拟体内养条件.
使用文献和试点BE研究数据验证和重新优化PBBM.
应用PBBM用于未来的BE预测,灵敏度分析和疗效评估 (光线/肠细胞度).
使用的Dissoflux工具用于不同配方的比较透性分析.

主要成果:

一个经过验证的PBBM成功预测了mesalamine肠涂片的体内养行为.
虚拟生物等价性研究证明了该模型的可预测性.
参数灵敏度分析确定了影响体内表现的关键生理因素.
模型预测了相应的光线和肠细胞度,支持治疗疗效.

结论:

开发的生物预测模型和介质可促进对梅萨拉肠膜涂层片的具有挑战性的生物等价性预测.
这种方法提高了对影响体内药物性能和疗效的因素的理解.
该研究为优化配方开发和确保治疗等效性提供了一个框架.

关键词:

美国的 PBBM PBBM 生物等价性生物等价性生物预测生物预测结肠度结肠度结肠度溶解流的流量其他气体.梅萨胺是一种胺.

更多相关视频

Self-Nanoemulsification of Healthy Oils to Enhance the Solubility of Lipophilic Drugs

Self-Nanoemulsification of Healthy Oils to Enhance the Solubility of Lipophilic Drugs

Published on: July 27, 2022

In vitro Digestion of Emulsions in a Single Droplet via Multi Subphase Exchange of Simulated Gastrointestinal Fluids

In vitro Digestion of Emulsions in a Single Droplet via Multi Subphase Exchange of Simulated Gastrointestinal Fluids

Published on: November 18, 2022

相关概念视频

Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

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...

Factors Influencing Drug Absorption: Drug Dissolution

Factors Influencing Drug Absorption: Drug Dissolution

The pharmacokinetic journey of drugs from solid oral dosage forms into systemic circulation is multifaceted. It begins with disintegration, a prerequisite ensuring a solid dosage form's subdivision into minute particles. Dissolution occurs next as these granulated entities solubilize in gastrointestinal fluids. This solubilization is crucial for the succeeding stage, permeation, which describes the traversal of the drug across the intestinal membrane and its subsequent entry into the blood...

Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH

Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH

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.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...

Factors Influencing Drug Absorption: Pharmaceutical Parameters

Factors Influencing Drug Absorption: Pharmaceutical Parameters

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...

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...

Factors Influencing Drug Absorption: Physicochemical Parameters

Factors Influencing Drug Absorption: Physicochemical Parameters

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...