Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles

Authors

  • Jayanth Panyam,

    1. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025, Omaha, Nebraska 68198
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  • Deborah Williams,

    1. Department of Physics and Astronomy, University of Nebraska, Lincoln, Nebraska 68588
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  • Alekha Dash,

    1. Department of Pharmacy Sciences, Creighton University Medical Center, Omaha, Nebraska 68178
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  • Diandra Leslie-Pelecky,

    1. Department of Physics and Astronomy, University of Nebraska, Lincoln, Nebraska 68588
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  • Vinod Labhasetwar

    Corresponding author
    1. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025, Omaha, Nebraska 68198
    2. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198
    • Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025, Omaha, Nebraska 68198 Telephone: 402-559-9021; Fax 402-559-9543
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Abstract

Biodegradable nanoparticles formulated from poly(D,L-lactide-co-glycolide) (PLGA) and polylactide (PLA) polymers are being extensively investigated for various drug delivery applications. In this study, we hypothesize that the solid-state solubility of hydrophobic drugs in polymers could influence their encapsulation and release from nanoparticles. Dexamethasone and flutamide were used as model hydrophobic drugs. A simple, semiquantitative method based on drug–polymer phase separation was developed to determine the solid-state drug–polymer solubility. Nanoparticles using PLGA/PLA polymers were formulated using an emulsion–solvent evaporation technique, and were characterized for size, drug loading, and in vitro release. X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) were used to determine the physical state of the encapsulated drug. Results demonstrated that the solid-state drug–polymer solubility depends on the polymer composition, molecular weight, and end-functional groups (ester or carboxyl) in polymer chains. Higher solid-state drug–polymer solubility resulted in higher drug encapsulation in nanoparticles, but followed an inverse correlation with the percent cumulative drug released. The XRD and DSC analyses demonstrated that the drug encapsulated in nanoparticles was present in the form of a molecular dispersion (dissolved state) in the polymer, whereas in microparticles, the drug was present in both molecular dispersion and crystalline forms. In conclusion, the solid-state drug–polymer solubility affects the nanoparticle characteristics, and thus could be used as an important preformulation parameter. © 2004 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 93:1804–1814, 2004

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