Hydrophilic matrix tablets, osmotic systems, and coated multiparticulates comprise the most prevalent modified release oral dosage forms. Materials, technologies, and release mechanisms for controlled drug delivery are selected depending on the site and desired rate or mode of drug release. Swellable matrices have many advantages, including simplicity of fabrication and drug delivery rate definition, development, and optimization. Furthermore, the availability of different grades of swellable excipients can help the design of appropriate release kinetics by capitalizing on non-Fickian diffusion behavior. These considerations can make swellable matrices attractive for controlling drug release.
Dipartimento Farmaceutico, Via G.P.Usberti 27/A, 43100, Parma, Italy e-mail: [email protected]
C.G. Wilson and P.J. Crowley (eds.), Controlled Release in Oral Drug Delivery, Advances in Delivery Science and Technology, DOI 10.1007/978-1-4614-1004-1_11, © Controlled Release Society 2011
Fig. 11.1 Sector of a disk matrix made of HPMC and the orange colored drug Buflomedil pyridoxal phosphate, in which water penetrated from the lateral side only. E erosion front, D diffusion front, S swelling front. Bottom left corner: matrix glassy core; Top right corner: solvent
Swellable matrix compacts are moving boundary systems in which control of drug release is dictated by rate of hydration, swelling, and dissolution of the polymer/ drug mixture. This sequence leads to boundary formation, i.e., fronts separating different physical regions inside the matrix during swelling (Fig. 11.1). These can determine the drug release kinetics. The swelling front separates glassy from rubbery polymer. In this location, physical stresses are created by polymer chain relaxation that determine matrix volume increase. Hence, swelling controls drug release.
Two other fronts determine release kinetics in a swellable matrix:
• The diffusion front, i.e., the boundary separating solid/undissolved drug from drug in solution; this can coincide with the swelling front.
• The matrix or erosion front, separating the swollen matrix from the solvent.
The distance between the swelling and erosion fronts defines the thickness of the gel layer. This in turn is a characteristic parameter of the diffusion layer for drug transport. Within the gel layer, concentration gradients (profiles) of polymer, water, and drug are established. Such profiles are generally depicted as linear since the swelling develops slowly. Consequent to this slow process, the local concentration may relax the variations in front position. This explains why in certain cases when the fronts move in a synchronized manner and the release area is constant, zero-order release can be obtained from such moving boundary systems. Thus, in swellable matrices the release area, i.e., the matrix surface exposed to the solvent, defines the release rate and kinetics. In general, the exposed area expands until erosion/dissolution phenomena counteract such increase, due to progressive disentanglement of the swollen polymeric chains.
This chapter illustrates how the swelling/release areas of matrices (geometry) can be used to design an appropriate release profile aligned with drug plasma profile requirements. Such control of the releasing area during swelling and dissolution determines release rate and kinetics without modifying the composition of the swellable system.
The concept of geometric manipulation to affect release rate and kinetics was introduced by Langer. Langer used inert matrices where diffusion layer thickness increases during release along with progressive increase of the diffusion front area . Three examples of such geometric manipulation are presented in this chapter, reflecting research activity and experience of the authors.
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