Pharmaceutical nanotechnology Controlled drug release from hydrogel-based matrices: Experiments and modeling Diego CACCAVO a , Sara CASCONE a , Gaetano LAMBERTI a, *, Anna Angela BARBA b a Department of Industrial Engineering, Via Giovanni Paolo II, 134, University of Salerno, 84084 Fisciano (SA), Italy b Department of Pharmacy, Via Giovanni Paolo II, 134, University of Salerno, 84084 Fisciano (SA), Italy A R T I C L E I N F O Article history: Received 12 February 2015 Received in revised form 21 March 2015 Accepted 25 March 2015 Available online 28 March 2015 Chemical compounds studied in this article: Hydroxypropyl-methylcellulose-HPMC (PubChem CID: 57503849) Theophylline (PubChem CID: 2153) Keywords: Hydrogels Water uptake Texture analysis Transport phenomena Modeling A B S T R A C T Controlled release by oral administration is mainly achieved by pharmaceuticals based on hydrogels. Once swallowed, a matrix made of hydrogels experiences water up-take, swelling, drug dissolution and diffusion, polymer erosion. The detailed understanding and quantification of such a complex behavior is a mandatory prerequisite to the design of novel pharmaceuticals for controlled oral delivery. In this work, the behavior of hydrogel-based matrices has been investigated by means of several experimental techniques previously pointed out (gravimetric, and based on texture analysis); and then all the observed features were mathematically described using a physical model, defined and recently improved by our research group (based on balance equations, rate equations and swelling predictions). The agreement between the huge set of experimental data and the detailed calculations by the model is good, confirming the validity of both the experimental and the theoretical approaches. ã 2015 Elsevier B.V. All rights reserved. 1. Introduction Hydrogels are widely used in the pharmaceutical preparations and, among them, the hydroxypropyl methylcellulose (HPMC) is the most extensively appreciated due to its physical, chemical, and biological properties (Phadtare et al., 2014). In fact, this polymer plays a key role in solid and liquid preparations, sustained and controlled release formulations, capsule production, gel, and bio-adhesive preparations (Huichao et al., 2014). For the adminis- tration of pharmaceuticals, the oral route has been and probably will continue to be the most exploited one thanks to the high patients compliance. The development of controlled release devices suitable for this application has seen in the hydrogel- based tablets the best option to the purpose. These systems benefit from their simplicity of production, low development costs and their highly adaptability in delivering different active molecules. The drug release from HPMC tablets is a complex process, which has been the topic of extensive research in the past few decades. If an hydrogel-based tablet enters in contact with a solvent, which penetrates inside the matrix, the polymer undergoes a relaxation process, due to the unfolding of the polymeric chains. A glass– rubbery transition occurs and a gel-like layer is formed (Grassi et al., 2007). In this region, the elongated chains allow the dissolved drug to easily diffuse and reach the dissolution medium. Once the polymer network have been completely hydrated and the chains disentanglement takes place, the matrix starts to erode. For hydrophilic polymer-based systems, swelling and erosion are the most important mechanisms and, while the swelling implies an increase of the matrix volume, the erosion causes a volume decrease, thus the time dependence of matrix volume is determined by the combined and opposing action of these two phenomena (Grassi and Grassi, 2014). Concerning the drug release from hydrophilic matrices, it can be influenced by several factors, which depend on the drug (such as its molecular weight, solubility, particle size distribution, and the initial dose), on the polymer used (such as its molecular weight, composition, structure, and viscosity) (Tahara et al., 1995), on formulation (such as the geometry of the matrix, excipients presence, and manufacturing process) (Sung et al., 1996), on external factors (such as the dissolution medium composition, ionic strength, and temperature) (Maderuelo et al., 2011; Zuleger and Lippold, 2001). Thus, it is clear the difficulty of a full understanding and characterization of all the phenomena involved in the drug release from these systems. During the last decades, several approaches have been used to describe the behavior of these systems, from both the experimen- tal and the modeling point of view. To study the swelling behavior * Corresponding author. Tel.: +39 089964077; fax: +39 089964057. E-mail address: glamberti@unisa.it (G. LAMBERTI). http://dx.doi.org/10.1016/j.ijpharm.2015.03.054 0378-5173/ ã 2015 Elsevier B.V. All rights reserved. International Journal of Pharmaceutics 486 (2015) 144–152 Contents lists available at ScienceDirect International Journal of Pharmaceutics journa l home page : www.e lsevier.com/loca te/ijpharm