Drug partitioning and release characteristics of tricyclic antidepressant drugs using a series of related hydrophilic-hydrophobic copolymers.
A series of crosslinked polymer networks formed from hydrophilic polyethylene oxide (PEO) and a hydrophobic polysiloxane (PGPMDMS) were studied with respect to the partitioning and release of five tricyclic antidepressants (TCAs) at pH 7.4. The TCAs, chemical analogues of one another, have both nonpolar and ionic characteristics at pH 7.4, but differ considerably in hydrophobicity. In PEO-PGPMDMS copolymer networks, the partition coefficient of protriptyline (the TCA studied most extensively) was observed to be higher than in networks of PEO or PGPMDMS singly. This finding, which may represent adsorption of the amphiphilic drug at interfacial sites between hydrophilic and hydrophobic phases within the copolymeric network, shows that in some cases, higher drug loadings of amphiphilic drugs can be obtained with a hydrophilic-hydrophobic copolymer compared with a material made of only one polymer. As the PEO content in PEO-PGPMDMS networks was increased from 20 to 100%, the release rate of protriptyline increased by greater than 1000-fold. Thus, a key variable in achieving a desired release rate is the PEO content of the copolymer. On the other hand, release rates of the five TCAs from PEO-PGPMDMS networks containing 50% PEO varied by a factor of less than 3. Thus, minimal effect on drug release rates was obtained by using a different TCA analogue.
Sung
C
C
Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139.
Raeder
J E
JE
Merrill
E W
EW
D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004058:Diffusion; D007700:Kinetics; D011092:Polyethylene Glycols; D011108:Polymers; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D000929:Antidepressive Agents, Tricyclic; D003692:Delayed-Action Preparations; D011108:Polymers; D011092:Polyethylene Glycols