title: Simple measurements for prediction of drug release from polymer matrices - Solubility parameters and intrinsic viscosity.
abstract: OBJECTIVE
  This study describes how protein release from polymer matrices correlate with simple measurements on the intrinsic viscosity of the polymer solutions used for casting the matrices and calculations of the solubility parameters of polymers and solvents used.
  
  
  METHODS
  Matrices of poly(dl-lactide-co-glycolide) (PLGA) were cast with bovine serum albumin (BSA) as a model drug using different solvents (acetone, dichloromethane, ethanol and water). The amount of released protein from the different matrices was correlated with the Hildebrand and Hansen solubility parameters of the solvents, and the intrinsic viscosity of the polymer solutions. Matrix microstructure was investigated by transmission and scanning electron microscopy (TEM and SEM). Polycaprolactone (PCL) matrices were used in a similar way to support the results for PLGA matrices.
  
  
  RESULTS
  The maximum amount of BSA released and the release profile from PLGA matrices varied depending on the solvent used for casting. The maximum amount of released BSA decreased with higher intrinsic viscosity, and increased with solubility parameter difference between the solvent and polymer used. The solvent used also had an effect on the matrix microstructure as determined by TEM and SEM. Similar results were obtained for the PCL polymer systems.
  
  
  CONCLUSIONS
  The smaller the difference in the solubility parameter between the polymer and the solvent used for casting a polymer matrix, the lower will be the maximum protein release. This is because of the presence of smaller pore sizes in the cast matrix if a solvent with a solubility parameter close to the one of the polymer is used. Likewise, the intrinsic viscosity of the polymer solution increases as solubility parameter differences decrease, thus, simple measurements of intrinsic viscosity and solubility parameter difference, allow the prediction of protein release profiles.
authors: Faculty of Health and Medical Sciences, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark. Electronic address: claus.madsen@sund.ku.dk.
authors: Claus G
authors: CG
authors: Madsen
authors: Faculty of Health and Medical Sciences, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark. Electronic address: anders.skov@gmail.com.
authors: Anders
authors: A
authors: Skov
authors: Faculty of Health and Medical Sciences, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark. Electronic address: stefania.baldursdottir@sund.ku.dk.
authors: Stefania
authors: S
authors: Baldursdottir
authors: Faculty of Health and Medical Sciences, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark. Electronic address: thomas.rades@sund.ku.dk.
authors: Thomas
authors: T
authors: Rades
authors: Faculty of Health and Medical Sciences, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark. Electronic address: lene.jorgensen@sund.ku.dk.
authors: Lene
authors: L
authors: Jorgensen
authors: School of Pharmacy, University of Otago, Dunedin, New Zealand. Electronic address: natalie.medlicott@otago.ac.nz.
authors: Natalie J
authors: NJ
authors: Medlicott
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D014783:Viscosity
chemical_list: D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid
keywords: Bovine serum albumin; Drug delivery systems; Medical device; Polymer matrices; Protein release; Therapeutic proteins