BIOPHARMACEUTICS AND PHARMACOKINETICS PDF
Applied Biopharmaceutics & Pharmacokinetics, 7e. Leon Shargel, Andrew B.C. Yu. Search Textbook Autosuggest Results. Chapter 1: Introduction to. Biopharmaceutics and Pharmacokinetics are complementary disciplines, being the former focused to study the interaction between the dosage form and the. PDF | Besides the stabilization of unstable drugs, the modification of the pharmacokinetics/biopharmaceutics was published by Frornming and Weyermann.
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BIOPHARMACEUTICS & PHARMACOKINETICS. Bio – life. Pharmaceutics. – general area of study concerned with. the formulation, manufacture, stability. Biopharmaceutics and Pharmacokinetic Introduction. Student Objectives for this Chapter. After completing the material in this chapter each. Textbook of Biopharmaceutics and Clinical Pharmacokinetics. By. S. NIAZI. Appleton-Century-Crofts, Madison Ave., New York,. NY pp.
Drug absorption requires that drugs cross one or more layers of cells and cell membranes.
Solubility is manipulated mainly by the structure of the drug. In general, solubility is inversely proportional to the number and type of lipophilic functions within the molecule and tightness of the crystal packing of the molecule.
Solubility decreases when there is increase in crystal packing or lipophilicity.
The concentration of drug in solution is the driving force of the membrane transfer of drug into the body, and low aqueous solubility often continues to present itself as a problem even after formulation improvements. Factors that influence drug absorption through oral route are: Biological factors: Permeation of the drug across the membrane, GI transit, site specificity, first-pass metabolism, metabolism in the liver, excretion as bile, excretion through bladder, and protein binding of drugs Pharmaceutical factors: Excipients, type of dosage forms, process of preparation, stability testing, and storage directions Other factors: Solubility of the drug; partitioning properties; dissociation characteristics; salt formation; particle size, shape, volume, and its distribution; crystallinity; polymorphism; prodrugs; and stereotype and its formation [ 8 , 13 , 14 ] 8.
Drug absorption Drugs may be either weak acids or bases that exist in both ionized and non-ionized forms in the body.
Drug in the non-ionized form is sufficiently soluble in membrane lipids and can cross cell membranes. The rate of absorption depends upon the ratio of the two forms at a particular site and is also a factor in distribution and elimination.
The protonated form of a weak acid is non-ionized, whereas the protonated form of a weak base is ionized.
The pKa is the negative log of the ionization constant, particular for each acidic or basic drug. Protonated form predominates when the pH is less than the pKa, whereas nonprotonated form predominates when pH is greater than the pKa.
In the stomach, with a pH of 1, weak acids and bases are highly protonated.
Weak acids are absorbed without dissociation than weak base from the stomach and exactly opposite in the intestine where weak bases are absorbed readily than weakly acidic drugs. In intestine, weakly acidic drugs are also found to be absorbed even though they are ionized due to the large surface area [ 15 ].
Absorption takes place across the biological membrane by two methods. Lipid drugs are absorbed by transcellular mechanism where the drug distributes into the lipid core of the membrane which diffuses into the other side of the membrane.
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The solute may also diffuse across the cell membrane and enter into the circulation. Another mechanism is the paracellular absorption.
The aqueous-filled pores in between the cells aid absorption of the drugs. Water-soluble drugs are readily absorbed, but the molecule size of the particle plays an important role [ 5 , 12 ]. Drug absorption through transcellular and paracellular pathways is shown in Figure 1. Figure 1. Drug absorption through transcellular and paracellular pathways 9.
Transport across cell membranes 9. Passive diffusion The concentration gradient provides energy for the transportation of the drug across the membrane, and also partitioning of the drug in favor of the lipid membrane decides the quantity of the drug absorbed. The unionized drug is absorbed markedly higher than the ionized form. It postulates that the flux goes from regions of high concentration to regions of low concentration, with a magnitude that is proportional to the concentration gradient, or in simplistic terms, the concept that a solute will move from a region of high concentration to a region of low concentration across a concentration gradient.
Active transport Active transport is the movement of molecules across the lipid cell membrane against concentration gradient, i. The absorption sites are at a specific place in the GIT.
[PDF] Epub Applied Biopharmaceutics Pharmacokinetics, Seventh Edition Full Online
Active transport is usually associated with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. This active transport process uses chemical energy, such as from adenosine triphosphate ATP.
These energy molecules are site specific — the drugs are transported at a particular site in the GIT, they are limited in number, and they act like a ferry service: it picks a molecule from the GIT, ferries across, leaves in the cytoplasm, and comes back to pick another molecule.
Endocytosis Endocytosis is an energy-using process by which cells absorb molecules such as proteins by engulfing them. It is used by large polar molecules that cannot pass through the hydrophobic plasma or cell membrane.
The opposite process is exocytosis. Phagocytosis is a specific form of endocytosis involving the vascular internalization of solids such as bacteria by an organism and is therefore distinct from other forms of endocytosis such as the vesicular internalization of various liquids pinocytosis.
[PDF] Epub Applied Biopharmaceutics Pharmacokinetics, Seventh Edition Full Online
Phagocytosis is involved in the acquisition of nutrients for some cells. Pinocytosis, otherwise known as cell drinking, fluid endocytosis, and bulk-phase pinocytosis, is a mode of endocytosis in which small particles are brought into the cell, forming an invagination and then suspended within small vesicles [ 14 , 16 - 21 ].
Various types of endocytosis are shown in Figure 2. Figure 2. Various pathways of endocytosis Models for drug absorption Various in vitro, in situ, and in vivo tools and techniques are used to characterize the absorption of drug substance to determine the rate and extent of absorption.
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Various models from low-throughput in situ rat model to high-throughput in silico models are used. Screening models for absorption such as human colon adenocarcinoma cell lines Caco-2 and HT are widely used; recently, MDCK cell line is used as an alternative one.
Other in vitro methods are: Cell culture models In vitro cell culture models have been utilized to assess the permeability and metabolism of drugs, to elucidate molecular mechanism of drug transport to provide information on pathways of drug degradation, and to explore the influence of structure in the absorption of new chemical entities.
Chapter 1 forms an excellent review of the X-ray physics underpinning X-ray emission spectrometry. Chapters 2 and 3 are devoted to wavelength and energy dispersive XRF resulting from X-ray excitation, these being the most commonly used techniques. Although, inevitably, much old ground is covered here, nevertheless the chapters contain much useful information and highlight recent instrument developments.
Chapters 5 and 6 relate to quantitative analysis for infinitely thick and intermediate thickness samples, respectively and Chapter 13 which might have been better placed directly after Chapters 5 and 6 discusses sample preparation. All chapters contain a large number of references and although there is some overlapping material between chapters, each chapter is reasonably complete in itself.
Although a given laboratory may not be interested in all the information in the hand-book, it nevertheless provides a most useful review and should have an essential place on the shelf of any laboratory practising X-ray emission spectrometry and related topics.
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S-GEL London, ISBN o Yu, Prentice-Hall International, The third edition of this textbook follows the successful format of previous editions. It starts with a review of the mathematical foundations of pharmacokinetics. This will be of particular benefit to students approaching the subject for the first time. In the third edition this chapter has been expanded to include some basic statistics.
Subsequent chapters give comprehensive coverage of phannacokinetic concepts and their application to both the clinical setting and research and development. As in previous editions of the textbook good use is made of illustrative examples and this edition includes an increased number of questions designed to promote reflection and provide practice in problem solving.Endocytosis Endocytosis is an energy-using process by which cells absorb molecules such as proteins by engulfing them.
The absorption sites are at a specific place in the GIT. In this theory, the diffrsivity D may not be independent o f saturation concentration Cs. Absorption o f ionized drug 3. Such an inhibitory effect of the various buffer cations on the drug transfer rate is in the following order: The commonly used lubricants are hydrophobic in nature several metallic stearates and waxes and known to inhibit wettability, penetration o f water into tablet and their disintegration and dissolution.