title: Release of gentamicin sulphate from biodegradable PLGA-implants produced by hot melt extrusion.
abstract: For a long-term local treatment of osteomyelitis biodegradable poly(lactic-co-glycolic acid) (PLGA) implants loaded with gentamicin sulphate (GS) were prepared, analysed and compared to the marketed product Septopal (Biomet, Darmstadt, Germany), which consists of polymethylmethacrylate (PMMA) beads loaded with the same active ingredient. The implants were manufactured by hot melt extrusion with a twin screw extruder. In order to decrease the processing temperature and to improve the drug release behaviour, polyethylene glycol 400 (PEG 400) was added as plasticizer in different concentrations. The glass transition temperature of PLGA measured by differential scanning calorimetry declined in the same manner as the extrusion temperature with increasing PEG 400 concentration. The extrudates of all batches exhibited good encapsulation efficiency between 85% and 115% of the specified content. The behaviour of the implants during exposure to a release medium were characterised by scanning electron microscopy, gravimetric analysis and finally in vitro drug release studies. The results suggest that drug liberation is not affected by the addition of PEG 400, and depends on the drug-PLGA ratio only. Extrudates with 25% GS showed a release pattern with an initially higher drug release followed by a zero order kinetic for about four weeks and showed release profiles equivalent to Septopal.
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University of Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gosau
authors.forename: B W
authors.initials: BW
authors.lastname: Müller
mesh_terms: D020341:Absorbable Implants; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding / Q000379:methods; D005079:Excipients; D005839:Gentamicins / Q000008:administration & dosage / Q000737:chemistry*; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D010968:Plasticizers; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D014867:Water / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D005079:Excipients; D005839:Gentamicins; D010968:Plasticizers; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid