Manufacture and release characteristics of Elvax polymers containing glutamate receptor antagonists.
Implantable sustained-release polymers offer an alternative to osmotic minipumps for the local delivery of drugs to specific brain areas. Here we describe the production of Elvax polymers containing a range of glutamate receptor antagonists and the quantitative characterization of their release properties. Sections of Elvax (200 or 400 microns), prepared by a dimethyl sulphoxide-based method, containing the NMDA antagonist MK-801 or the non-NMDA antagonist CNQX exhibited similar release profiles: an initial 2-week burst followed by a slow decline in release rate over the next 6 weeks. Differences in slice preparation method and thickness or drug concentration and solubility all led to alterations in the level of drug release, but not the overall exponential nature of the release curve. Elvax sections prepared by an aqueous method containing the NMDA antagonists CPP or APV displayed more constant but much lower levels of release than those from the dimethyl sulphoxide-based method. The in vitro release characteristics were compared with in vivo release of MK-801 and the close correspondence observed indicates that the in vitro release data is an accurate predictor of the drug release behaviour of implanted Elvax slices.
University Laboratory of Physiology, Oxford, UK.
A L
AL
Smith
P M
PM
Cordery
I D
ID
Thompson
D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000493:pharmacokinetics; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers; D004343:Drug Implants; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D005289:Ferrets; D008970:Molecular Weight; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics; D011145:Polyvinyls; D017470:Receptors, Glutamate / Q000187:drug effects*
D004337:Drug Carriers; D004343:Drug Implants; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D011145:Polyvinyls; D017470:Receptors, Glutamate; C016438:ethylenevinylacetate copolymer; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid