Modeling of drug release from collagen matrices.
Drug release from collagen matrices is in most cases governed by diffusion from swollen matrices but also enzymatic matrix degradation or hydrophobic drug/collagen interactions may contribute. To reduce water uptake and to prolong the release, insoluble collagen matrices have been chemically or dehydrothermally crosslinked. Assuming Fickian diffusion a one-dimensional model was developed and tested that allows description of water penetration, swelling and drug release and that may be expanded considering a subsequent erosion process or interactions. Swelling is described by a volume balance. For dry collagen matrices crosslinked by thermal treatment the existence of a moving front separating the polymer from a gel phase was considered, and a convective term induced by the volume expansion was incorporated. The resulting moving boundary problem was solved using a method based on biquadratic finite elements in both space and time that is stable, shows high accuracy, and is suitable for solving problems with a singularity at the initial time point. The model was verified for insoluble collagen matrices at different crosslinking degrees for both chemical and thermal treatment. For constant diffusion coefficients a close form of the solution was derived yielding equivalent results to the numerical approach.
Radu
Florin A
FA
Department of Pharmaceutical Technology, University of Erlangen, Cauerstr. 4, D-91058 Erlangen, Germany.
Bause
Markus
M
Knabner
Peter
P
Lee
Geoffrey W
GW
Friess
Wolfgang C
WC
D000818:Animals; D002417:Cattle; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D012995:Solubility
D004364:Pharmaceutical Preparations; D011108:Polymers; D003094:Collagen