Drug Delivery System
Online ISSN : 1881-2732
Print ISSN : 0913-5006
ISSN-L : 0913-5006
Volume 25, Issue 4
Displaying 1-6 of 6 articles from this issue
Feature articles “New challenge for oral drug delivery” Editor : Shinji Yamashita
  • Ryusuke Takano
    2010 Volume 25 Issue 4 Pages 362-370
    Published: 2010
    Released on J-STAGE: November 05, 2010
    JOURNAL FREE ACCESS
    The number of poorly water-soluble drug candidates in drug discovery has recently increased. Limited solubility often causes poor and variable oral absorption. Therefore, it is critical to predict poor absorption of a candidate compound at the drug discovery stage. Herein is a summary of our strategy for improving oral absorption of poorly water-soluble drugs using a computer-based simulation.
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  • Claudia da Costa Mathews, Kiyohiko Sugano
    2010 Volume 25 Issue 4 Pages 371-374
    Published: 2010
    Released on J-STAGE: November 05, 2010
    JOURNAL FREE ACCESS
    Numerous methodologies have been suggested and practically applied to improve the ability to market drug candidates whose development is limited by drug solubility and dissolution rate. These include the use of wetting agents, complexing agents such as cyclodextrins, preparation of high energy drug states related to polymorphic transformations and the use of particle size manipulation. One suggested path forward is the use of a "spring and parachute" approach wherein a technique such as self emulsifying systems allow rapid dissolution of a poorly water-soluble drug at a supersaturated concentration.
    However, this in vivo supersaturated system has the potential to precipitate which will impact negatively on the pharmacokinetics and efficacy of the drug. A formulation component which hinders crystal growth or nucleation then acts as a parachute to stabilise the metastable supersaturated system in vivo is the key to improve the oral absorption of a drug1,2).
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  • Ikumi Tamai
    2010 Volume 25 Issue 4 Pages 375-383
    Published: 2010
    Released on J-STAGE: November 05, 2010
    JOURNAL FREE ACCESS
    Intestinal influx transporters are useful for the improvement of intestinal membrane permeability of drugs and/or pharmacologically active compounds under development. Peptide transporters PEPT1 accept various peptide-mimetics and transport them in a pH dependent manner. Three strategies to utilize PEPT1 are described, depending on the characteristics of the pharmacologically active compounds, including prodrug approaches and formulation technology. The first is for amino acid like compounds such as L-dopa. An addition of amino acid moiety to the pharmacologically active compound to be peptide mimetics is useful to be transported by PEPT1. The second is for peptide-like compounds which are not transported well by PEPT1. Cephalosporin antibiotic, cefixime, exhibited pH dependent transport via PEPT1 and the optimal pH to be transported by PEPT1 is more acidic than physiological intestinal luminal pH. In such case, acidification of intestinal lumen by acidic polymers such as Eudragit L100-55 can enhance PEPT1-mediated permeability without prodrug approach. The third is for non-amino acid or -peptide like compounds. Simple addition of peptide moiety to the pharmacologically active compounds is useful, since the attached peptide moiety could be accepted as substrate of PEPT1, while there is certain structural requirement for the modification to be accepted by PEPT1 well. The examples of those three strategies are described. Furthermore, organic anion transporting polypeptides OATPs such as OATP1A2 and OATP2B1 are likely involved as the intestinal absorptive transporters based on the effects of co-administered fruit juices and genetic polymorphisms of OATP2B1 on the absorption of OATP substrates in human as well as in vitro transport studies. Further characterization of intestinal OATPs should be essential to utilize them as the tools for the improvement of drug absorption.
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  • utilization of enteric coating agents that start to dissolve at higher pH
    Fumié K Tanno, Shinji Sakuma, Hiroyasu Kokubo, Shinji Yamashita
    2010 Volume 25 Issue 4 Pages 384-391
    Published: 2010
    Released on J-STAGE: November 05, 2010
    JOURNAL FREE ACCESS
    It is known that a gradual increase in pH is observed on passing through the small intestine. We designed enteric-coated dosage forms that start to disintegrate when they reach the middle-to-lower region of the small intestine, with the aim of circumventing food-drug interactions that reduce the bioavailability of drugs taken after a meal(negative food effects). The low absorption of a drug with the negative food effect in fed dogs was improved when the drug was administered orally as dosage forms enteric-coated with hypromellose acetate succinate(HPMCAS)that dissolves at pH above 7, which corresponds to pH at the ileum. Data indicated that food-drug interactions were avoided by separating the main absorption site of drugs from that of food components.
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  • Noriyasu Kamei, Mariko Morishita
    2010 Volume 25 Issue 4 Pages 392-402
    Published: 2010
    Released on J-STAGE: November 05, 2010
    JOURNAL FREE ACCESS
    Oral absorption of therapeutic peptides and proteins is significantly limited because of their poor permeability through the intestinal mucosal epithelium and instability in intestine and circulation. Therefore, we have currently attempted to develop the oral dosing form of these macromolecular drugs using cell-penetrating peptides (CPPs), which have strong ability to bring other molecules into numerous cells. Here, we reviewed the current researches using CPPs as drug delivery carrier, and also referred to our studies examining the usefulness of CPPs on the improvement of intestinal peptides and proteins absorption. In addition, we showed the applicability of CPPs to their nasal administration and the mechanisms associated with the absorption enhancing effect of CPPs. CPPs will be promising tool to realize the sufficient absorption of therapeutic peptides and proteins via noninvasive delivery routes.
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  • Shinji Sakuma, Ken-ichiro Hiwatari, Robert M Hoffman, Shinji Yamashita
    2010 Volume 25 Issue 4 Pages 403-410
    Published: 2010
    Released on J-STAGE: November 05, 2010
    JOURNAL FREE ACCESS
    Peanut agglutinin(PNA)-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide)(PNVA)chains encapsulating coumarin 6 were designed as a novel colonoscopic imaging agent. PNA was a targeting moiety that binds to β-D-galactosyl-(1-3)-N-acetyl-D-galactosamine, which is the terminal sugar of the Thomsen-Friedenreich antigen that is specifically expressed on the mucosal side of colorectal cancer cells. PNVA was immobilized with the aim of reducing nonspecific interactions between imaging agents and normal tissues. Coumarin 6 was encapsulated into nanosphere cores to provide endoscopically detectable fluorescence intensity. It is anticipated that the lectin-immobilized fluorescent nanospheres specifically accumulate on the surface of tumor tissues in the large intestine with resulting fluorescence. Real-time and accurate diagnosis of small-sized early colorectal cancer can be then achieved through observation of a clear fluorescence contrast between the normal and tumor tissues using the florescent endoscopy.
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