2. Academic Validation
  3. Self-emulsifying drug delivery systems: Impact of stability of hydrophobic ion pairs on drug release

Self-emulsifying drug delivery systems: Impact of stability of hydrophobic ion pairs on drug release

  • Int J Pharm. 2019 Apr 20;561:197-205. doi: 10.1016/j.ijpharm.2019.03.001.
Imran Nazir 1,  Mulazim Hussain Asim 2,  Aida Dizdarević 3,  Andreas Bernkop-Schnürch 4
Affiliations

Affiliations

  • 1 Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria; Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan.
  • 2 Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria; Department of Pharmaceutics, Faculty of Pharmacy, University of Sargodha, 40100 Sargodha, Pakistan.
  • 3 Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
  • 4 Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
PMID: 30836151 DOI: 10.1016/j.ijpharm.2019.03.001
Abstract

The aim of this study was to evaluate the impact of stability of hydrophobic ion pairs (HIPs) in gastrointestinal (GI) fluids on their release from self-emulsifying Drug Delivery systems (SEDDS). HIPs of leuprolide (LEU), Insulin (INS) and bovine serum albumin (BSA) were formed using various mono- and di-carboxylate Surfactants i.e. sodium deoxycholate (SDC), sodium dodecanoate (SDD), sodium stearoyl glutamate (SSG) and pamoic acid di-sodium salt (PAM). HIPs were evaluated regarding precipitation efficiency, log Pn-butanol/water and dissociation behavior at various pH and ionic strength. Solubility studies of these HIPs were accomplished to identify suitable solvents for the formulation of SEDDS. Subsequently, HIPs were incorporated into SEDDS followed by characterization regarding zeta potential, stability and log DSEDDS/release medium. Independent from the type of (poly)Peptides, PAM showed most efficient HIP properties among tested Surfactants. The highest encapsulation efficiency with PAM was achieved at molar ratios of 1:1 for LEU, 1:3 for INS and 1:50 for BSA and log Pn-butanol/water of HIPs were increased at least 2.5 units. Dissociation studies showed that LEU-PAM, INS-PAM, BSA-PAM complexes were dissociated within 6 h up to 25%, 60% and 85% in GI fluids, respectively. These HIPs were successfully incorporated into SEDDS exhibiting negative zeta potential and high stability for 4 h. Log DSEDDS/release medium of LEU-PAM, INS-PAM, BSA-PAM complexes were 2.4 ± 0.7, 2.1 ± 0.62 and 1.6 ± 0.45, respectively. Findings of this study showed that stability of HIPs has great impact on log DSEDDS/release medium and consequently on their release from SEDDS.

Keywords

(Poly)peptides; Dissociation; Hydrophobic ion pair; Pamoic acid; Self-emulsifying drug delivery system (SEDDS); log D(SEDDS/release medium).

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