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Moiety valdecoxib and propionic acid through enzymatic conversion that occurs primarily in the liver.93 An exciting new field of parenteral drug delivery involves oil-based depot formulations for protein delivery. The feasibility of administering such polar drug substances in the form of oil solutions is governed by the attainment of sufficient oil solubility, which can be achieved with prodrugs. Interesting examples of the experimental peptide delivery formulations are 4-imidazolidinone...

Principles of Prodrug Design

Successful design of prodrug-based controlled delivery systems is generally based on efficient transformation of the promoiety into the active drug in vivo at the desired organ or tissue. Despite the diversity in chemical structure, most prodrugs can be classified on the basis of a common chemical linkage (e.g., esters, amides, and salts). In addition to these common types of prodrugs, recent prodrug approaches include conversion of promoieties into primary and secondary amines, imides,...

Lung

The lung as a drug delivery site offers many advantages. Drugs can be delivered noninvasively via lung for systemic effects. A rich blood supply and large effective surface area (140 m2) contributes to a high bioavailability and a quick onset of action.117 Delivery of proteins and peptides may be feasible owing to the low metabolic activity of this surface.117 Anatomy and physiology. The human respiratory system is divided into upper and lower respiratory tracts. The upper respiratory system...

Prodrugs for ocular delivery

For most ocularly applied drugs, passive diffusion is thought to be the main transport process across the cornea.67 Major challenges in ocular drug delivery include the tightness of the cornea1 epithelium barrier, rapid precorneal drug elimination, and systemic absorption from the conjunctiva.68,69 As a result, less then 10 percent and typically less than 1 percent of the instilled dose reaches the intraocular tissues. Many drugs developed for systemic use lack the physicochemical properties...

Anant Shanbhag Noymi Yam and Bhaskara Jasti

Long School of Pharmacy and Health Sciences University of the Pacific Stockton, California 3.2 Rationale for Prodrug Design 77 3.3 Principles of Prodrug Design 78 3.3.1 Ester-based prodrugs 79 3.3.2 Amide-based prodrugs 82 3.3.3 Salt-based prodrugs 84 3.3.4 Additional prodrug types 86 3.4 Prodrugs for Prolonged Therapeutic Action 88 3.5 Prodrug Design for Various Routes of Administration 89 3.5.1 Prodrugs for nasal delivery 90 3.5.2 Prodrugs for ocular delivery 91 3.5.3 Prodrugs for...

Tzuchi Rob Ju Yihong

Abbott Laboratories North Chicago, Illinois 4.1.1 Basic equations of diffusion 4.1.2 Diffusional release from a preloaded matrix 4.1.3 Diffusion across a barrier membrane 4.2 Oral Diffusion-Controlled Systems 4.2.3 Current challenges and future trends 4.3 Transdermal Diffusion-Controlled Systems 4.3.4 Current challenges and future trends 4.4 Other Diffusion-Controlled Systems 4.4.1 Intrauterine devices and intravaginal rings 4.4.3 Subcutaneous implants References

Macromoleculedirected enzyme prodrug therapy MDEPT

Macromolecule-directed enzyme prodrug therapy (MDEPT) is also referred to as polymer-directed prodrug therapy (PDEPT). It is similar to GDEPT and VDEPT, except that it applies a macromolecule conjugate of the drug to enable delivery to the tumor. This method also takes advantage of the enhanced permeation and retention (EPR) of tumors. One of the earliest examples of MDEPT involved -(2-hydroxypropyl) methacrylamide.116 The modes of delivery and activation of the prodrug by the preceding methods...

Ladme Scheme In Pharmacology

Figure 1.2 Relationship between the pharmacokinetic, link, and pharmacodynamic models. Figure 1.2 Relationship between the pharmacokinetic, link, and pharmacodynamic models. 1.3 LADME Scheme and Meaning of Pharmacokinetic Parameters The frequently used acronym LADME, which stands for liberation, absorption, distribution, metabolism, and excretion, broadly describes the various biopharmaceutical processes influencing the pharmacokinetics of a drug. Since each of aspect of LADME can influence the...

Introduction

Innovations in drug discovery and development, fueled by rapid advances in technology, have led to novel therapeutics for the prevention and treatment of diseases, greatly improving the quality of patients' lives. These innovations have been driven by increasing investments in research and development by pharmaceutical companies, which to some extent have contributed to the upward-spiraling costs of health care, especially prescription medications. The number of new molecular entities NMEs...

Zeren Wang and Rama A Shmeis

Boehringer-Ingelheim Pharmaceuticals, Inc. Ridgefield, Connecticut 5.2 Theoretical Considerations for Dissolution Controlled 140 Release Matrix and Coated Systems 5.2.1 Dissolution of solid particles 140 5.2.2 Dissolution of coated systems 142 5.2.3 Dissolution of matrix systems 146 5.3 Parameters for Design of Dissolution Controlled 149 Release Matrix and Coated Systems 5.3.1 Parameters affecting dissolution 149 of solid particles 5.3.2 Parameters affecting dissolution 150 of coated systems...

References

Principles of drug metabolism. In Abraham, D. J. ed. , Burgers Medicinal Chemistry and Drug Discovery, Vol 2, 6th ed. New York Wiley, 2003, pp. 431-498. 2. Albert, A. Chemical aspects of selective toxicity, Nature 182 421-423, 1958. 3. Harper, N. J. Drug latentiation. Prog. Drug Res. 4 221-294, 1962. 4. Sinkula, A., and Yalkowsky, S. Rationale for design of biologically reversible drug derivatives Prodrugs. J. Pharm. Sci. 64 181-210, 1975. 5. Higuchi, T., and Stella,...

Amit Kokate Venugopal P Marasanapalle Bhaskara R Jasti and Xiaoling Li

Long School of Pharmacy and Health Sciences University of the Pacific Stockton, California 2.2 Barriers to Peroral Controlled Release Drug Delivery 42 of the gastrointestinal tract 42 2.2.2 Physiological and biochemical characteristics of the gastrointestinal tract 48 2.2.3 Barriers to peroral drug delivery 52 2.3 Barriers to Nonperoral Controlled Release Drug Delivery 52 2.4 Physiological and Biochemical Barriers to Controlled Release Drug Delivery 66 Copyright 2006 by The...

Contributors

Engineering Fellow, ALZA Corporation, a Johnson amp Johnson Company, Mountain View, Calif. chap. 7 Bret Berner, Ph.D. Vice President, Depomed, Inc., Menlo Park, Calif. chap. 6 Shiladitya Bhattacharya, M. Pharm. Ph.D. Candidate, Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, Calif. chap. 13 Ramesh R. Boinpally, Ph.D. Research Investigator, OSIPharmaceuticals, Boulder, Colo....