Pharmaceutical Research

, Volume 26, Issue 7, pp 1644–1656

PLGA and PHBV Microsphere Formulations and Solid-State Characterization: Possible Implications for Local Delivery of Fusidic Acid for the Treatment and Prevention of Orthopaedic Infections

  • Chiming Yang
  • David Plackett
  • David Needham
  • Helen M. Burt
Research Paper

DOI: 10.1007/s11095-009-9875-5

Cite this article as:
Yang, C., Plackett, D., Needham, D. et al. Pharm Res (2009) 26: 1644. doi:10.1007/s11095-009-9875-5
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Abstract

Purpose

To develop and characterize the solid-state properties of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) microspheres for the localized and controlled release of fusidic acid (FA).

Methods

The effects of FA loading and polymer composition on the mean diameter, encapsulation efficiency and FA released from the microspheres were determined. The solid-state and phase separation properties of the microspheres were characterized using DSC, XRPD, Raman spectroscopy, SEM, laser confocal and real time recording of single microspheres formation.

Results

Above a loading of 1% (w/w) FA phase separated from PLGA polymer and formed distinct spherical FA-rich amorphous microdomains throughout the PLGA microsphere. For FA-loaded PLGA microspheres, encapsulation efficiency and cumulative release increased with initial drug loading. Similarly, cumulative release from FA-loaded PHBV microspheres was increased by FA loading. After the initial burst release, FA was released from PLGA microspheres much slower compared to PHBV microspheres.

Conclusions

A unique phase separation phenomenon of FA in PLGA but not in PHBV polymers was observed, driven by coalescence of liquid microdroplets of a DCM-FA-rich phase in the forming microsphere.

KEY WORDS

antibioticscontrolled drug deliveryfusidic acidPLGA and PHBV microspheressolid-state phase separation

Abbreviations

BSEM

Backscattering SEM

DSC

Differential scanning calorimetry

FA

Fusidic acid

HV

Hydroxyvaleric acid

PHBV

Poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid)

PLGA

Poly(DL-lactic-co-glycolic acid)

PLLA

Poly(L -lactic acid)

PMMA

Poly(methylmethacrylate)

SEM

Scanning electron microscopy

Tg

Glass transition temperature

Tm

Melting temperature

Tr

Enthalpy relaxation temperature

XRPD

X-ray powder diffraction

ΔHm

Enthalpy of melting

ΔHr

Enthalpy relaxation

Supplementary material

11095_2009_9875_MOESM1_ESM.avi (5.3 mb)
ESM 1 (AVI 5.34 MB)

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Chiming Yang
    • 1
  • David Plackett
    • 2
  • David Needham
    • 3
  • Helen M. Burt
    • 1
  1. 1.Faculty of Pharmaceutical SciencesThe University of British ColumbiaVancouverCanada
  2. 2.Risø National Laboratory for Sustainable EnergyTechnical University of Denmark—DTURoskildeDenmark
  3. 3.Department of Mechanical Engineering and Material ScienceDuke UniversityDurhamUSA