Pharmacology of Intestinal Permeation I


Book Description

The intestine, particularly the small bowel, represents a large surface (in the adult 2 human approximately 200m ) through which the body is exposed to its environment. A vigorous substrate exchange takes place across this large surface: nutrients and xenobiotics are absorbed from the lumen into the bloodstream or the lymph, and simultaneously, the same types of substrate pass back into the lumen. The luminal surface of the intestine is lined with a "leaky" epithelium, thus the passage of the substrates, in either direction, proceeds via both transcellular and intercellular routes. Simple and carrier-mediated diffusion, active transport, pinocytosis, phagocytosis and persorption are all involved in this passage across the intestinal wall. The term "intestinal permeation" refers to the process of passage of various substances across the gut wall, either from the lumen into the blood or lymph, or in the opposite direction. "Permeability" is the condition of the gut which governs the rate of this complex two-way passage. The pharmacologist's interest in the problem of intestinal permeation is twofold: on the one hand, this process determines thebioavailability of drugs and contributes significantly to the pharmacokinetics and toxicokinetics of xeno biotics; on the other hand, the pharmacodynamic effects of many drugs are manifested in a significant alteration of the physiological process of intestinal permeation.




Pharmacology of Intestinal Permeation II


Book Description

The intestine, particularly the small bowel, represents a large surface (in the adult 2 human approximately 200 m ) through which the body is exposed to its environ ment. A vigorous substrate exchange takes place across this large surface: nutrients and xenobiotics are absorbed from the lumen into the bloodstream or the lymph, and simultaneously, the same types of substrate pass back into the lumen. The luminal surface of the intestine is lined with a "leaky" epithelium, thus the passage of the substrates, in either direction, proceeds via both transcellular and intercellular routes. Simple and carrier-mediated diffusion, active transport, pinocytosis, phagocytosis and persorption are all involved in this passage across the intestinal wall. The term "intestinal permeation" refers to the process of passage of various substances across the gut wall, either from the lumen into the blood or lymph, or in the opposite direction. "Permeability" is the condition of the gut which governs the rate of this complex two-way passage. The pharmacologist's interest in the problem of intestinal permeation is twofold: on the one hand, this process determines the bioavailability of drugs and contributes significantly to the pharmacokinetics and toxicokinetics of xeno biotics; on the other hand, the pharmacodynamic effects of many drugs are manifested in a signigicant alteration of the physiological process of intestinal permeation.




Concepts and Models for Drug Permeability Studies


Book Description

This book intends to be an updated compilation of the most important buccal, gastric, intestinal, pulmonary, nasal, vaginal, ocular, skin and blood-brain barrier in vitro models for predicting the permeability of drugs. Concepts and Models for Drug Permeability Studies focuses on different approaches and comprises of various models. Each model describes the protocol of seeding and conservation, the application for specific drugs, and takes into account the maintenance of physiologic characteristics and functionality of epithelium, from the simplest immortalized cell-based monoculture to the most complex engineered-tissue models. Chapters also discuss the equivalence between in vitro cell and tissue models and in vivo conditions, highlighting how each model may provisionally resemble a different drug absorption route. - Updated information regarding the most recent in vitro models to study the permeability of drugs - Short and concise chapters covering all the biological barriers with interest in drug permeability - A combination of bibliographic information related with individual models and footnote instructions of technical procedures for construction of cell and tissue-based models - Simple and clear scientific content, adaptable for young scientists and experimented researchers




Oral Drug Absorption


Book Description

Oral Drug Absorption, Second Edition thoroughly examines the special equipment and methods used to test whether drugs are released adequately when administered orally. The contributors discuss methods for accurately establishing and validating in vitro/in vivo correlations for both MR and IR formulations, as well as alternative approaches for MR an




Drug Absorption Studies


Book Description

This is a well thought-out, highly practical text covering contemporary ‘in vitro’ techniques for drug absorption studies. Starting at the molecular level of investigation, it continues with cell monolayer models (both primary and cell lines) and culminates with in situ techniques as a final testing format. In addition, chapters on high-throughput assays, in vitro-in vivo correlation, bioinformatics and regulatory issues are covered, giving a comprehensive overview of available models and techniques. Moreover, an appendix consisting of a number of practical protocols is available online, updated as needed, and should prove very helpful to apply the techniques directly to the benchside.










Biopharmaceutics


Book Description

Explore the latest research in biopharmaceutics from leading contributors in the field In Biopharmaceutics - From Fundamentals to Industrial Practice, distinguished Scientists from the UK's Academy of Pharmaceutical Sciences Biopharmaceutica Focus Group deliver a comprehensive examination of the tools used within the field of biopharmaceutics and their applications to drug development. This edited volume is an indispensable tool for anyone seeking to better understand the field of biopharmaceutics as it rapidly develops and evolves. Beginning with an expansive introduction to the basics of biopharmaceutics and the context that underpins the field, the included resources go on to discuss how biopharmaceutics are integrated into product development within the pharmaceutical industry. Explorations of how the regulatory aspects of biopharmaceutics function, as well as the impact of physiology and anatomy on the rate and extent of drug absorption, follow. Readers will find insightful discussions of physiologically based modeling as a valuable asset in the biopharmaceutics toolkit and how to apply the principles of the field to special populations. The book goes on to discuss: Thorough introductions to biopharmaceutics, basic pharmacokinetics, and biopharmaceutics measures Comprehensive explorations of solubility, permeability, and dissolution Practical discussions of the use of biopharmaceutics to inform candidate drug selection and optimization, as well as biopharmaceutics tools for rational formulation design In-depth examinations of biopharmaceutics classification systems and regulatory biopharmaceutics, as well as regulatory biopharmaceutics and the impact of anatomy and physiology Perfect for professionals working in the pharmaceutical and biopharmaceutical industries, Biopharmaceutics - From Fundamentals to Industrial Practice is an incisive and up-to-date resource on the practical, pharmaceutical applications of the field.




Hyperbranched Polydendrons


Book Description

This thesis outlines the first synthesis of a new complex branched polymer architecture that aims to combine the benefits of dendrimers with the simplicity of conventional polymerisation. There is no other available literature on these remarkable materials, dubbed hyperbranched polydendrons, due to their novelty. The new materials were shown to have very high molecular weights (>1,000,000 g/mol), exceptional self-assembly and encapsulation behaviour and unparalleled functionalisation capabilities, and were studied pharmacologically to determine their potential as oral nanomedicine candidates. The detailed investigation of the chemical variables involved in synthesising hyperbranched polydendrons has shown that their self-assembly and pharmacological behaviour can be turned on and off and fine-tuned by altering the composition of the materials. The permeation of the self-assembled particles through model gut epithelium suggests the potential for oral dosing of drug loaded nanomedicines that result in circulating nanoparticles – a research goal that is currently being pursued by several groups around the globe.