Atomistic simulation study of surfactant and polymer interactions on the surface of a fenofibrate crystal.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Author(s): Zhu W;Zhu W; Romanski FS; Meng X; Mitra S; Tomassone MS
  • Source:
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2011 Apr 18; Vol. 42 (5), pp. 452-61. Date of Electronic Publication: 2011 Feb 01.
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, Non-P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Science B.V Country of Publication: Netherlands NLM ID: 9317982 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0720 (Electronic) Linking ISSN: 09280987 NLM ISO Abbreviation: Eur J Pharm Sci Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam : Elsevier Science B.V
      Original Publication: Amsterdam ; New York : Elsevier, c1993-
    • Subject Terms:
      Models, Chemical* ; Models, Molecular*; Excipients/*chemistry ; Fenofibrate/*chemistry ; Polymers/*chemistry ; Surface-Active Agents/*chemistry; Crystallization ; Drug Stability ; Glucans/chemistry ; Hypromellose Derivatives ; Methylcellulose/analogs & derivatives ; Methylcellulose/chemistry ; Molecular Structure ; Polysorbates/chemistry ; Sodium Dodecyl Sulfate/chemistry ; Solubility ; Surface Properties ; Technology, Pharmaceutical
    • Abstract:
      It is currently of great interest to the pharmaceutical industry to control the size and agglomeration of nano- and micro-particles for the enhancement of drug delivery. Typically, surfactants and polymers are used as additives to interact with and stabilize the growing crystal surface, thus controlling size and agglomeration; however, selection is traditionally done empirically or using heuristics. The objective of this study was to use molecular dynamic simulations to investigate and predict additive interactions, and thus, evaluate the stabilization potential of individual and multiple additives on the surface of the model drug fenofibrate. Non-ionic surfactant Tween 80, anionic surfactant sodium dodecyl sulfate (SDS), and polymers hydroxypropyl methylcellulose (HPMC) and Pullulan were evaluated individually on three distinct crystal surfaces [(001), (010), (100)], as well as in surfactant-polymer combinations. HPMC was determined to have the strongest interaction with the surfaces of the fenofibrate crystal, and therefore, was predicted to be the most effective individual additive. A mixture of HPMC with SDS was determined to be the most effective mixture of additives, and more effective than HPMC alone, indicating a synergistic effect. The predictions of mixed additives indicated a relative order of effectiveness as follows: HPMC-SDS>HPMC-Tween 80>Pullulan-Tween 80>Pullulan-SDS. The simulations were subsequently validated by an anti-solvent crystallization of fenofibrate where it was found that HPMC individually, and a mixture of HPMC-SDS, produced the smallest and most stable crystals, as measured by laser diffraction; this, in combination with measurements of the crystal growth rate in the presence and absence of additives confirmed the results of the simulations.
      (Copyright © 2011 Elsevier B.V. All rights reserved.)
    • Accession Number:
      0 (Excipients)
      0 (Glucans)
      0 (Polymers)
      0 (Polysorbates)
      0 (Surface-Active Agents)
      368GB5141J (Sodium Dodecyl Sulfate)
      3NXW29V3WO (Hypromellose Derivatives)
      8ZQ0AYU1TT (pullulan)
      9004-67-5 (Methylcellulose)
      U202363UOS (Fenofibrate)
    • Publication Date:
      Date Created: 20110205 Date Completed: 20110801 Latest Revision: 20151119
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.ejps.2011.01.009
    • Accession Number:
      21291999