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Characterization of a Liquid Crystal System for Sustained Release of a Peptide BMS-686117

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Abstract

Liquid crystal lipid-based formulations are an effective approach to prolong pharmacokinetics and reduce burst release of a drug on subcutaneous delivery. The objective of this paper was to investigate the influence of phase structures of a lipid-based liquid crystal delivery system and its associated mechanical properties on the release profile of a peptide. It was hypothesized that release of drug molecules are closely related to the mechanical properties that are controlled by phase structures. Experimentally, the relationship between phase structures of lipid liquid crystal system—soy phosphatidyl choline (SPC) and glycerol dioleate (GDO) in water were characterized by polarized light microscopy and small angle X-ray diffraction. Their rheological properties were evaluated with a rheometer and the in vitro release of the peptide as a measure drug release from the LC-depot injection. Three phases: disordered phase, lamellar phase, mixtures of cubic, lamellar, and hexagonal phases were detected by varying formulation compositions. A significant difference in rheological behavior was observed. The disordered phase displayed some attributes of typical Newtonian fluid with lowest viscosity while the lamellar phase showed a shear thinning behavior. Regarding the mechanical strength, the lamellar phase presents the highest storage modulus due to its layer structure followed by mixed phases. Comparing release profiles, the lamellar phase produced a fast release followed by the mixture of phases. In conclusion, this study demonstrates the ability to characterize LC phase structures with microscopy, small angle X-ray diffraction, and rheological measurements and their link to modulating a peptide release profile.

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Acknowledgements

Authors thank Alex Baranowski for the help on liquid crystal preparation and Dr. Hussain for reviewing the manuscript.

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Authors and Affiliations

  1. DMPK & Clinical Pharmacology, Acerta Pharma BV, Redwood City, California, 94065, USA

    Yan Xu

  2. Bishop University, Sherbrooke, Québec, J1M 1Z7, Canada

    Vivian Li

  3. Drug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, New Jersey, 08903, USA

    Jinjiang Li, Duohai Pan & Neil Mathias

  4. Anton Paar The Americans, Ashland, Virginia, 23005, USA

    Gerd Langenbucher

Authors
  1. Yan Xu
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  2. Vivian Li
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  3. Jinjiang Li
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  6. Neil Mathias
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Correspondence to Yan Xu.

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Xu, Y., Li, V., Li, J. et al. Characterization of a Liquid Crystal System for Sustained Release of a Peptide BMS-686117. AAPS PharmSciTech 19, 348–357 (2018). https://doi.org/10.1208/s12249-017-0835-9

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  • DOI: https://doi.org/10.1208/s12249-017-0835-9

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