TITLE

Synthesis and In Vitro Skin Permeation of Naproxen Conjugates with a- Alkylamino Acids

AUTHOR(S)
Pignatello, Rosario; Montenegro, Lucia; Stancampiano, Annalisa H. S.; Puelo, Antonina; Puglisi, Giovanni
PUB. DATE
June 2005
SOURCE
Current Drug Delivery;Jun2005, Vol. 2 Issue 2, p185
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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 that of NAP, while the higher homologues (3) and (4) were more lipophilic than the parent drug, as assessed by CLogP and HPLC methods. The chemical and enzymatic hydrolysis of these compounds was evaluated in aqueous buffer solution (pH 7.4) and 80% human plasma. All compounds showed a good chemical stability (t1 / 2 = 88-133 h) but underwent a rapid enzymatic hydrolysis to NAP (t1 / 2_around 3 h). The bioconversion of prodrugs into NAP was confirmed by an in vivo test, since i.p. administration of compounds 2-4 to mice gave a similar analgesic response than the parent drug. In vitro skin permeation experiments were performed using adult human SCE samples mounted in Franz-type diffusion cells. The butyl derivative 2 that showed an increased aqueous solubility compared to NAP gave a 5-fold improvement of skin permeation compared to NAP. In conclusion, the conjugate 2 could be regarded as a good candidate to improve NAP topical delivery and will be further studied as a prodrug for topical administration of this drug.
ACCESSION #
16677599

 

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...

  • Design of Prodrugs to Enhance Colonic Absorption by Increasing Lipophilicity and Blocking Ionization. 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 // Pharmaceuticals;Feb2014, Vol. 7 Issue 2, p207 

    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...

  • Formulation Development and Characterization of Naproxen Sodium-Loaded Mucoadhesive Microspheres. Kumar, K. Saravana; Reddy, P. Jayachandra; Chandra Sekhar, K.B. // Journal of Pharmaceutical Sciences & Research;2012, Vol. 4 Issue 2, p1709 

    Development of new drug molecule is expensive and time consuming. Improving the safety efficacy ratio of old drugs has been attempted using different methods such as individualizing drug therapy and therapeutic drug monitoring. Delivering drug at controlled rate, slow delivery, and targeted...

  • Enhancement of Dissolution Rate of Naproxen by Lipid Based Solid Dispersions. Nagabandi, Vijaykumar; Chandragiri, Anil Kumar; Thota, Sridhar; Katakam, Pragathi // Journal of Pharmaceutical Sciences & Research;2014, Vol. 6 Issue 2, p78 

    Oral dosage forms have always been considered the preferred route of delivery due to their lower unit dose cost and ease of compliance. Approximately 40-70% of new chemical entities (NCE'S) display poor oral absorption characteristics, generally as a result of poor solubility, poor dissolution...

  • 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.,...

  • 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...

  • Topical Delivery of a Naproxen-Dithranol Co-drug: In Vitro Skin Penetration, Permeation, and Staining. Lau, Wing; White, Alex; Heard, Charles // Pharmaceutical Research;Dec2010, Vol. 27 Issue 12, p2734 

    Purpose: This work probed the topical delivery and skin-staining properties of a novel co-drug, naproxyl-dithranol (Nap-DTH), which comprises anti-inflammatory (naproxen) and anti-proliferative (dithranol) moieties. Method: Freshly excised, full-thickness porcine ear skin was dosed with...

  • Formulation and evaluation of indomethacin biomicroparticles. Sudeep, Gupta; Pawan, Gaur; Kulwant, Soam; Ruchi, Suyal; Vinod, Rana; Prashant, Dabral // Journal of Pharmacy & Bioallied Sciences;Mar2012 Supplement, pS27 

    Indomethacin microparticles prepared by extraction of bio polymer from arachis hypogen. in vitro drug release study was carried out through egg shell membrane for 3 hrs and analyzed sample by UV spectroscopy at 320 nm. A novel bio membrane from arachis hypogen was isolated by simplify economical...

  • Amphiphilic Transdermal Permeation Enhancers: Structure-Activity Relationships. V�vrov�, K.; Zbytovsk�, J.; Hrab�lek, A. // Current Medicinal Chemistry;2005, Vol. 12 Issue 19, p2273 

    Transdermal drug delivery offers numerous advantages over conventional routes of administration; however, poor permeation of most drugs across the skin barrier constitutes a serious limitation of this methodology. One of the approaches used to enlarge the number of transdermally-applicable drugs...

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