PMID- 19384471 OWN - NLM STAT- MEDLINE DCOM- 20090817 LR - 20211020 IS - 1573-904X (Electronic) IS - 0724-8741 (Linking) VI - 26 IP - 7 DP - 2009 Jul TI - 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. PG - 1644-56 LID - 10.1007/s11095-009-9875-5 [doi] AB - 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. FAU - Yang, Chiming AU - Yang C AD - Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver BCV6T1Z3, Canada. FAU - Plackett, David AU - Plackett D FAU - Needham, David AU - Needham D FAU - Burt, Helen M AU - Burt HM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090421 PL - United States TA - Pharm Res JT - Pharmaceutical research JID - 8406521 RN - 0 (Anti-Bacterial Agents) RN - 0 (Delayed-Action Preparations) RN - 0 (Glycolates) RN - 0 (Polyesters) RN - 0 (poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate)) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 26009-03-0 (Polyglycolic Acid) RN - 33X04XA5AT (Lactic Acid) RN - 59XE10C19C (Fusidic Acid) SB - IM MH - Anti-Bacterial Agents/*chemistry MH - Calorimetry, Differential Scanning MH - Delayed-Action Preparations/*chemistry MH - Fusidic Acid/*chemistry MH - Glycolates/*chemistry MH - Kinetics MH - Lactic Acid MH - *Microspheres MH - Particle Size MH - Phase Transition MH - Polyesters/*chemistry MH - Polyglycolic Acid MH - Polylactic Acid-Polyglycolic Acid Copolymer MH - Powder Diffraction MH - Surface Properties MH - X-Ray Diffraction EDAT- 2009/04/23 09:00 MHDA- 2009/08/18 09:00 CRDT- 2009/04/23 09:00 PHST- 2008/09/23 00:00 [received] PHST- 2009/03/16 00:00 [accepted] PHST- 2009/04/23 09:00 [entrez] PHST- 2009/04/23 09:00 [pubmed] PHST- 2009/08/18 09:00 [medline] AID - 10.1007/s11095-009-9875-5 [doi] PST - ppublish SO - Pharm Res. 2009 Jul;26(7):1644-56. doi: 10.1007/s11095-009-9875-5. Epub 2009 Apr 21.