Pluronic-functionalized silica-lipid hybrid microparticles: improving the oral delivery of poorly water-soluble weak bases

Shasha Rao, Katharina Richter, Tri-Hung Nguyen, Benjamin James Boyd, Christopher John Porter, Angel Tan, Clive Allan Prestidge

Research output: Contribution to journalArticleResearchpeer-review

Abstract

A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.
Original languageEnglish
Pages (from-to)4424-4433
Number of pages10
JournalMolecular Pharmaceutics
Volume12
Issue number12
DOIs
Publication statusPublished - 2015

Keywords

  • drug precipitation
  • oral bioavailability improvement
  • Pluronic
  • poorly water-soluble drug
  • silica-lipid hybrid
  • weak bases

Cite this

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title = "Pluronic-functionalized silica-lipid hybrid microparticles: improving the oral delivery of poorly water-soluble weak bases",
abstract = "A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.",
keywords = "drug precipitation, oral bioavailability improvement, Pluronic, poorly water-soluble drug, silica-lipid hybrid, weak bases",
author = "Shasha Rao and Katharina Richter and Tri-Hung Nguyen and Boyd, {Benjamin James} and Porter, {Christopher John} and Angel Tan and Prestidge, {Clive Allan}",
year = "2015",
doi = "10.1021/acs.molpharmaceut.5b00622",
language = "English",
volume = "12",
pages = "4424--4433",
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Pluronic-functionalized silica-lipid hybrid microparticles: improving the oral delivery of poorly water-soluble weak bases. / Rao, Shasha; Richter, Katharina; Nguyen, Tri-Hung; Boyd, Benjamin James; Porter, Christopher John; Tan, Angel; Prestidge, Clive Allan.

In: Molecular Pharmaceutics, Vol. 12, No. 12, 2015, p. 4424-4433.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Pluronic-functionalized silica-lipid hybrid microparticles: improving the oral delivery of poorly water-soluble weak bases

AU - Rao, Shasha

AU - Richter, Katharina

AU - Nguyen, Tri-Hung

AU - Boyd, Benjamin James

AU - Porter, Christopher John

AU - Tan, Angel

AU - Prestidge, Clive Allan

PY - 2015

Y1 - 2015

N2 - A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.

AB - A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.

KW - drug precipitation

KW - oral bioavailability improvement

KW - Pluronic

KW - poorly water-soluble drug

KW - silica-lipid hybrid

KW - weak bases

UR - http://pubs.acs.org.ezproxy.lib.monash.edu.au/doi/pdf/10.1021/acs.molpharmaceut.5b00622

U2 - 10.1021/acs.molpharmaceut.5b00622

DO - 10.1021/acs.molpharmaceut.5b00622

M3 - Article

VL - 12

SP - 4424

EP - 4433

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

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ER -