Hydrophilic matrices for controlled drug delivery: an improved mathematical model to predict the resulting drug release kinetics (the "sequential layer" model).
OBJECTIVE
The aims of this study were (i) to elucidate the transport mechanisms involved in drug release from hydrophilic matrices; and (ii) to develop an improved mathematical model allowing quantitative predictions of the resulting release kinetics.


METHODS
Our previously presented model has been substantially modified, by adding: (i) inhomogeneous swelling; (ii) poorly water-soluble drugs; and (iii) high initial drug loadings. The validity of the improved model has been tested experimentally using hydroxypropyl methylcellulose (HPMC)-matrices, containing either a poorly or a freely water-soluble drug (theophylline or chlorpheniramine maleate) at various initial loadings in phosphate buffer pH 7.4 and 0.1 N HCl, respectively.


RESULTS
By overcoming the assumption of homogeneous swelling we show that the agreement between theory and experiment could be significantly improved. Among others, the model could describe quantitatively even the very complex effect on the resulting relative release rates (first slowing down, then accelerating drug release) observed when increasing the initial loading of poorly water-soluble drugs.


CONCLUSIONS
The practical benefit of this work is an improved design model that can be used to predict accurately the required composition and dimensions of drug-loaded hydrophilic matrices in order to achieve desired release profiles, thus facilitating the development of new pharmaceutical products.
Siepmann
J
J
College of Pharmacy, Freie Universität Berlin, Germany. siepmann@med.univ-angers.fr
Peppas
N A
NA
D002626:Chemistry, Pharmaceutical; D002744:Chlorpheniramine / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004058:Diffusion; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry*; D008956:Models, Chemical; D015203:Reproducibility of Results; D012995:Solubility; D013806:Theophylline / Q000737:chemistry; D014867:Water / Q000737:chemistry
D003692:Delayed-Action Preparations; D014867:Water; D065347:Hypromellose Derivatives; D002744:Chlorpheniramine; D008747:Methylcellulose; D013806:Theophylline