TY - JOUR
T1 - Dense nanolipid fluid dispersions comprising ibuprofen
T2 - Single step extrusion process and drug properties
AU - Morrison, Eric D.
AU - Guo, Molin
AU - Maia, João
AU - Nelson, Doug
AU - Swaminathan, Suresh
AU - Kandimalla, Karunya K.
AU - Lee, Hanseung
AU - Zasadzinski, Joseph
AU - McCormick, Alon
AU - Marti, James
AU - Garhofer, Brian
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - 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.
AB - 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.
KW - Dermal permeation
KW - Hot-melt extrusion
KW - Ibuprofen
KW - Lipid nanocarriers
KW - Nanoparticles
KW - Topical drug delivery
KW - pH stat titration drug release method
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U2 - 10.1016/j.ijpharm.2021.120289
DO - 10.1016/j.ijpharm.2021.120289
M3 - Article
C2 - 33556488
AN - SCOPUS:85101550371
SN - 0378-5173
VL - 598
JO - International journal of pharmaceutics
JF - International journal of pharmaceutics
M1 - 120289
ER -