title: Microencapsulation of hydrophilic drug substances using biodegradable polyesters. Part II: Implants allowing controlled drug release--a feasibility study using bisphosphonates.
abstract: The prolonged delivery of hydrophilic drug salts from hydrophobic polymer carriers at high drug loading is an ambitious goal. Pamidronate disodium salt (APD) containing implants prepared from spray-dried microparticles were investigated using a laboratory ram extruder. An APD-containing polymer matrix consisting of an APD-chitosan implant embedded in the biodegradable polymer D,L-poly(lactide-co-glycolide acid-glucose) (PLG-GLU) was compared with a matrix system with the micronized drug distributed in the PLG-GLU. The APD-chitosan matrix system showed a triphasic release behaviour at loading levels of 6.86 and 15.54% (w/w) over 36 days under in-vitro conditions. At higher loading (31.92%), a drug burst was observed within 6 days due to the formation of pores and channels in the polymeric matrix. In contrast, implants containing the micronized drug showed a more continuous release profile over 48 days up to a loading of 31.78% (w/w). At a drug loading of 46.17% (w/w), a drug burst was observed. Using micronized drug salts and reducing the surface area available for diffusion, parenteral delivery systems for highly water-soluble drug candidates were shown to be technically feasible at high drug loadings.
authors.affiliation: Department of Pharmaceutics and Biopharmacy, Philipps-University, D-35032 Marburg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Weidenauer
authors.forename: D
authors.initials: D
authors.lastname: Bodmer
authors.forename: T
authors.initials: T
authors.lastname: Kissel
mesh_terms: D000277:Adjuvants, Pharmaceutic; D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D002686:Chitin / Q000031:analogs & derivatives*; D048271:Chitosan; D004164:Diphosphonates; D004339:Drug Compounding / Q000379:methods*; D004343:Drug Implants; D005240:Feasibility Studies; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D000077268:Pamidronate; D011091:Polyesters; D011100:Polyglycolic Acid; D013395:Sucrose; D013499:Surface Properties
chemical_list: D000277:Adjuvants, Pharmaceutic; D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D004164:Diphosphonates; D004343:Drug Implants; D011091:Polyesters; C489708:polymer D,L-poly(lactide-co-glycolide acid-glucose); D002686:Chitin; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013395:Sucrose; D048271:Chitosan; D000077268:Pamidronate