Using a drug to structure its release matrix and release profile.
Silicone elastomers have proven to be useful implantable release matrices for hydrophobic drugs. However, their utility for the release of hydrophilic materials is less well developed and, even with the addition of polar excipients such as poly(ethylene oxide) (PEO), burst release profiles are often observed-achieving longer term release is more challenging. We report that linoleic acid, initially used to solubilize polar, cationic nicotine in silicone precursors, additionally acted to change the internal morphology of resulting silicone+PEO elastomers. The unexpected consequence of this change was a change in the distribution of hydrophilic domains of PEO/drug within the silicone and the ability to control the rate of release of the drug in vitro. The relationship between excipients, silicone morphology, and release profile is examined.
Brook
Michael A
MA
Department of Chemistry, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada. mabrook@mcmaster.ca
Holloway
Alison C
AC
Ng
Kenneth K
KK
Hrynyk
Michael
M
Moore
Carly
C
Lall
Ryan
R
D002626:Chemistry, Pharmaceutical; D004343:Drug Implants; D005079:Excipients; D019787:Linoleic Acid / Q000737:chemistry; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D009538:Nicotine / Q000008:administration & dosage / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D012826:Silicone Elastomers; D012828:Silicones / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013501:Surface-Active Agents
D004343:Drug Implants; D005079:Excipients; D004364:Pharmaceutical Preparations; D012826:Silicone Elastomers; D012828:Silicones; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D009538:Nicotine; D019787:Linoleic Acid