Drug release mechanisms from heterogeneous interpenetrating networks

The objective of this research was to determine drug release mechanisms from HIPNs composed of a PTMO network and a copolymer of DMAAm and St. In order to gain a better understanding of the release mechanism the networks which compose the HIPN were studied separately. The DMAAm/St networks were synthesized with varying compositions of DMAAm and St. The aqueous swelling of these networks reflected their HPL/HPB balance and was characterized by the polymer-water interacation parameter. Drug release rates and water absorption rates were found to be independent of the drug solubility for copolymers that were hydrophilic in nature. The drug release rates and the absorption of water, however, became more dependent on the drug solubility as the copolymer become more hydrophobic. These effects were explained using the concepts of free volume and rate of water absorption. To study the PTMO component of the HIPN two series of networks were made in which the crosslinking density and topological structure were changed by altering the length of the PTMO or by changing the amount of diluent in the reaction mixture. The role of crosslinks and entanglements, in general, was discussed in relation to their contribution to the equilibrium swelling and elongation of polymer networks. For the PTMO network the polymer volume fraction in the relaxed state plays a key role in the release profile. When the volume of the relaxed state is large relative to its dry volume, the release of solute will be slower and the amount of water uptake will be greater than if the volume of the relaxed state is smaller. The release of a hydrophilic solute, such as sodium salicylate, from a hydrophobic PTMO network has a bimodal release profile. Water is absorbed by the network due to the presence of a hydrophilic solute as the hydrophobic networks show no swelling in water. The release profile is related to network elasticity and the relaxed state. Near zero order release can be seen over a period of may days with networks of very high elasticity and a small polymer volume fraction in the relaxed state. The drug solubility was shown to play a significant role in the release and water uptake of the PTMO network. The release mechanisms from the HPINs can best be described as a combination of the release mechanisms from the individual components. When the HIPN has a large amount of DMAAm the release was rapid and independent of the drug solubility. This was also seen with the DMAAm/St system at high ratios of DMAAm. Drug solubility did play a role in the rate of release when the network became more hydrophobic. In such cases the network experienced overswelling such as that seen with only PTMO. With even more hydrophobic networks the drug solubility plays a less significant role in the release mechanism.