Dense nanolipid fluid dispersions comprising ibuprofen: Single step extrusion process and drug properties

Eric D. Morrison, Molin Guo, João Maia, Doug Nelson, Suresh Swaminathan, Karunya K. Kandimalla, Hanseung Lee, Joseph Zasadzinski, Alon McCormick, James Marti, Brian Garhofer

Research output: Contribution to journalArticlepeer-review

Abstract

Dense nanolipid fluid (DNLF) dispersions are highly concentrated aqueous dispersions of lipid nanocarriers (LNCs) with more than 1015 lipid particles per cubic centimeter. Descriptions of dense nanolipid fluid dispersions in the scientific literature are rare, and they have not been used to encapsulate drugs. In this paper we describe the synthesis of DNLF dispersions comprising ibuprofen using a recently described twin-screw extrusion process. We report that such dispersions are stable, bind ibuprofen tightly and yet provide high transdermal drug permeation. Ibuprofen DNLF dispersions prepared according to the present study provide up to five times greater flux of the pharmacologically active S-ibuprofen isomer through human skin than a commercially available racemic ibuprofen emulsion product. We demonstrate scaling up the twin-screw extrusion method to pilot production for a stable, highly permeating ibuprofen DNLF composition based on excipients approved by the US FDA for use in topical products as a key step towards development of a commercially viable, FDA approvable topical ibuprofen medicine to treat osteoarthritis, which has never before been accomplished.

Original languageEnglish (US)
Article number120289
JournalInternational journal of pharmaceutics
Volume598
DOIs
StatePublished - Apr 1 2021
Externally publishedYes

Bibliographical note

Funding Information:
This material is based in part upon work supported by the National Science Foundation under SBIR Grant No. 1647292. Portions of this work were carried out in the Characterization Facility, University of Minnesota, a member of the NSF funded Materials Research Facilities Network (www.mrfn.org) via the MRSEC program. The Hitachi SU8320 cryo-SEM and Cryospecimen preparation system were provided by NSF MRI DMR-1229263. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nano Coordinated Infrastructure Network (NNCI) under Award Number ECCS-1542202. The authors also thank Drs. Vijay John and Jibao He for allowing use of the cryo-SEM in the coordinated instrumentation facility lab at Tulane University and gratefully acknowledged the donation of materials from BASF and Jeen International Corporation. Extension of surfactant-oil-water phase equilibria studies to phase dynamics which forms the basis of the work of this paper was a collaborative vision with the late Prof. H. Ted Davis of the University of Minnesota, to whom we are indebted.

Funding Information:
This material is based in part upon work supported by the National Science Foundation under SBIR Grant No. 1647292. Portions of this work were carried out in the Characterization Facility, University of Minnesota, a member of the NSF funded Materials Research Facilities Network (www.mrfn.org) via the MRSEC program. The Hitachi SU8320 cryo-SEM and Cryospecimen preparation system were provided by NSF MRI DMR-1229263. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nano Coordinated Infrastructure Network (NNCI) under Award Number ECCS-1542202. The authors also thank Drs. Vijay John and Jibao He for allowing use of the cryo-SEM in the coordinated instrumentation facility lab at Tulane University and gratefully acknowledged the donation of materials from BASF and Jeen International Corporation. Extension of surfactant-oil-water phase equilibria studies to phase dynamics which forms the basis of the work of this paper was a collaborative vision with the late Prof. H. Ted Davis of the University of Minnesota, to whom we are indebted.

Publisher Copyright:
© 2021 Elsevier B.V.

Keywords

  • Dermal permeation
  • Hot-melt extrusion
  • Ibuprofen
  • Lipid nanocarriers
  • Nanoparticles
  • Topical drug delivery
  • pH stat titration drug release method

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