TITLE

Design of Prodrugs to Enhance Colonic Absorption by Increasing Lipophilicity and Blocking Ionization

AUTHOR(S)
Nofsinger, Rebecca; Clas, Sophie-Dorothee; Sanchez, Rosa I.; Walji, Abbas; Manser, Kimberly; Nissley, Becky; Balsells, Jaume; Nair, Amrithraj; Qun Dang; Bennett, David Jonathan; Hafey, Michael; Junying Wang; Higgins, John; Templeton, Allen; Coleman, Paul; Grobler, Jay; Smith, Ronald; Yunhui Wu
PUB. DATE
February 2014
SOURCE
Pharmaceuticals;Feb2014, Vol. 7 Issue 2, p207
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Prodrugs are chemistry-enabled drug delivery modifications of active molecules designed to enhance their pharmacokinetic, pharmacodynamic and/or biopharmaceutical properties. Ideally, prodrugs are efficiently converted in vivo, through chemical or enzymatic transformations, to the active parent molecule. The goal of this work is to enhance the colonic absorption of a drug molecule with a short half-life via a prodrug approach to deliver sustained plasma exposure and enable once daily (QD) dosing. The compound has poor absorption in the colon and by the addition of a promoiety to block the ionization of the molecule as well as increase lipophilicity, the relative colonic absorption increased from 9% to 40% in the retrograde dog colonic model. A combination of acceptable solubility and stability in the gastrointestinal tract (GI) as well as permeability was used to select suitable prodrugs to optimize colonic absorption.
ACCESSION #
94716226

 

Related Articles

  • Prodrugs -- An Efficient Way to Breach Delivery and Targeting Barriers. Huttunen, Kristiina M.; Rautio, Jarkko // Current Topics in Medicinal Chemistry;Sep2011, Vol. 11 Issue 18, p2265 

    The study of prodrugs that are chemically modified bioreversible derivatives of active drug compounds to alter their undesired properties has been expanded widely during the last decades. Despite the commercial success the prodrugs have afforded, the concept is still quite unknown among many...

  • Synthesis and In Vitro Skin Permeation of Naproxen Conjugates with a- Alkylamino Acids. Pignatello, Rosario; Montenegro, Lucia; Stancampiano, Annalisa H. S.; Puelo, Antonina; Puglisi, Giovanni // Current Drug Delivery;Jun2005, Vol. 2 Issue 2, p185 

    Novel amide conjugates of the NSAID naproxen (NAP, 1) with short-chain a-alkylamino acids (C4 to C6 alkyl chain) were synthesized through a carbodiimide (EDAC)-assisted coupling reaction and evaluated as dermal prodrugs of NAP. The 2-a-aminobutyl derivative (2) showed lipophilicity similar to...

  • Modern Prodrug Design for Targeted Oral Drug Delivery. Arik Dahan; Zimmermann, Ellen M.; Ben-Shabat, Shimon // Molecules;Oct2014, Vol. 19 Issue 10, p16489 

    The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g.,...

  • Self Emulsifying Drug Delivery System : A Review. S, Padma priya; kumar, Patel Krunal; J, Kausalya; V., Ravichandiran // Journal of Pharmacy Research;Oct2011, Vol. 4 Issue 10, p3483 

    The oral delivery of hydrophobic drugs presents a major challenge because of the low aqueous solubility of such compounds. Self emulsifying drug delivery systems (SEDDS), which are isotropic mixtures of oils, surfactants, solvents and co solvents/surfactants can be used for the design of...

  • Strategies to Increase the Oral Bioavailability of Nucleoside Analogs. Lalanne, Muriel; Andrieux, Karine; Couvreur, Patrick // Current Medicinal Chemistry;Apr2009, Vol. 16 Issue 11, p1391 

    Nucleoside analogs are first line chemotherapy in various severe diseases: AIDS (acquired immunodeficiency disease syndrome), cytomegalovirus infections, cancer etc. However, most of these compounds suffer from poor bioavailability via oral route. In order to get around this drawback,...

  • Recent advances in self emulsifying drug delivery system - A review. Pathak, A.; Jain, V.; Nagariya, A. K.; Singh, R.; Nayak, S.; Bansal, P.; Gupta, V.; Kumar, S.; Singh, Harinder // Drug Invention Today;Feb2010, Vol. 2 Issue 2, p123 

    Self-emulsifying drug delivery systems (SEDDS) are usually used to improve the bioavailability of hydrophobic drugs. Approximately 40% of new chemical entities exhibit poor aqueous solubility and present a major challenge to modern drug delivery system, because of their low bioavailability. From...

  • Gastro Retentive Drug Delivery System- A Review. Gurnany, Ekta; Singhai, Priyanka; Soni, Arti; Jain, Rahul; Jain, Sunil K; Jain, Aviral // Journal of Pharmacy Research;Jun2011, Vol. 4 Issue 6, p1899 

    In recent years scientific and technological advancements have been made in research and development of oral drug delivery system. The reasons that the oral route achieved such popularity may be in part attributed to its ease of administration. Oral sustained drug delivery system is complicated...

  • Challenges for the oral delivery of macromolecules. Goldberg, Michael; Gomez-Orellana, Isabel // Nature Reviews Drug Discovery;Apr2003, Vol. 2 Issue 4, p289 

    The rapid integration of new technologies by the pharmaceutical industry has resulted in numerous breakthroughs in the discovery, development and manufacturing of pharmaceutical products. In particular, the commercial-scale production of high-purity recombinant proteins has resulted in important...

  • Colon Specific Drug Delivery Systems: A Review on Various Pharmaceutical Approaches. Prasanth, V. V.; Jayaprakash, R.; Mathew, Sam T. // Journal of Applied Pharmaceutical Science;2012, Vol. 2 Issue 1, p163 

    Colon specific drug delivery system has attracted considerable attention for the past few years in order to develop drug delivery systems that are able to release drugs specifically in the colon in a predictable and reproducible manner. The colon is a site where both local and systemic delivery...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics