A new model of resorbable device degradation and drug release - part I: zero order model

BACKGROUND: Within the field of resorbable devices, recent years have seen an increased demand for better reliability from drug delivery systems and resorbable polymer degradation control, causing researchers to abandon trial-and-error approaches towards model-based methods. In this context, we developed a lumped-parameters zero-order model for the degradation of resorbable polymeric drug release systems. Such a model is thought to be applicable in the design of specific devices based on the expected degradation time and drug delivery rates, as it is based on a ‘shrinking core’ approach and takes into account the main physicochemical parameters involved in polymer degradation, in drug release and in mechanical strength prediction, all independently estimated. RESULTS: The model, based on conservation equations, leads to numerically solved ordinary differential equations, the predictions of which were verified through literature data. Data of different authors and various systems were satisfactorily matched by model predictions, thus confirming the reliability of parameter estimation procedures. CONCLUSION: The present model is among the very few that completely address all aspects involved in device degradation and drug delivery altogether, and thus represents a step ahead with respect to current available solutions, firmly enforcing itself into the ongoing debate on the modelling of degradation and release behaviour. Copyright © 2008 Society of Chemical Industry

[1]  A. Göpferich,et al.  Polymer degradation and erosion : mechanisms and applications , 1996 .

[2]  James J. Carberry,et al.  Chemical and catalytic reaction engineering , 1976 .

[3]  M. Dentini,et al.  Scaffolds Based on Biopolymeric Foams , 2005 .

[4]  John Crank,et al.  Diffusion in polymers , 1968 .

[5]  Suming Li,et al.  Hydrolytic degradation of devices based on poly(DL-lactic acid) size-dependence. , 1995, Biomaterials.

[6]  S. Saha,et al.  Effects of molecular weight and small amounts of D-lactide units on hydrolytic degradation of poly(L-lactic acid)s , 2006 .

[7]  J. Siepmann,et al.  PLGA-based microparticles: elucidation of mechanisms and a new, simple mathematical model quantifying drug release. , 2002, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[8]  J. Siepmann,et al.  Mathematical modeling of bioerodible, polymeric drug delivery systems. , 2001, Advanced drug delivery reviews.

[9]  Degradation and drug‐release studies of a poly(glycolide‐co‐trimethylene carbonate) copolymer (Maxon) , 2005 .

[10]  H. Tsuji,et al.  Environmental degradation of biodegradable polyesters 1. Poly(ε-caprolactone), poly[(R)-3-hydroxybutyrate], and poly(L-lactide) films in controlled static seawater , 2002 .

[11]  S. Gogolewski,et al.  Effect of in vivo and in vitro degradation on molecular and mechanical properties of various low-molecular-weight polylactides. , 1997, Journal of biomedical materials research.

[12]  Robert Langer,et al.  Size and temperature effects on poly(lactic-co-glycolic acid) degradation and microreservoir device performance. , 2005, Biomaterials.

[13]  S. Saha,et al.  Enzymatic, alkaline, and autocatalytic degradation of poly(L-lactic acid): effects of biaxial orientation. , 2006, Biomacromolecules.

[14]  X. Zhu,et al.  Polymer microspheres for controlled drug release. , 2004, International journal of pharmaceutics.

[15]  B. Sabel,et al.  Small drug sample fabrication of controlled release polymers using the microextrusion method , 1998, Journal of Neuroscience Methods.

[16]  Davide Manca,et al.  Modeling the controlled release of microencapsulated drugs: theory and experimental validation , 2003 .

[17]  Andreas Greiner,et al.  Paclitaxel releasing films consisting of poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) and their potential as biodegradable stent coatings. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[18]  J M Anderson,et al.  Inflammatory response to implants. , 1988, ASAIO transactions.

[19]  G. Smith,et al.  Evaluation of in vitro drug release, pH change, and molecular weight degradation of poly(L-lactic acid) and poly(D,L-lactide-co-glycolide) fibers. , 2005, Tissue engineering.

[20]  R. Siegel Controlled release dosage form design , 2003 .

[21]  John Crank,et al.  The Mathematics Of Diffusion , 1956 .

[22]  Y. Inai,et al.  Melt spinning of poly(L-lactic acid) and its biodegradability , 2005 .

[23]  S. Siegel,et al.  Effect of drug type on the degradation rate of PLGA matrices. , 2006, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[24]  Jack L. Koenig,et al.  A review of polymer dissolution , 2003 .

[25]  F. Alexis Factors affecting the degradation and drug-release mechanism of poly(lactic acid) and poly[(lactic acid)-co-(glycolic acid)] , 2005 .

[26]  Michel Vert,et al.  Structure-property relationships in the case of the degradation of massive aliphatic poly-(α-hydroxy acids) in aqueous media , 1990 .

[27]  S. Venkatraman,et al.  Controlled release from bioerodible polymers: effect of drug type and polymer composition. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[28]  T. Karjalainen,et al.  Biodegradable lactone copolymers. III. Mechanical properties of ε‐caprolactone and lactide copolymers after hydrolysis in vitro , 1996 .

[29]  Paolo Colombo,et al.  Analysis of the swelling and release mechanisms from drug delivery systems with emphasis on drug solubility and water transport , 1996 .