Matrix drug delivery systems

Until recently, hot-melt extrusion had not received much attention in the pharmaceutical literature. Pellets comprising cellulose acetate phthalate were prepared using a rudimentary ram extruder in 1969 and studied for dissolution rates in relation to pellet geometry. More recently, production of matrices based on polyethylene and polycaprolactone were investigated using extruders of laboratory scale. Mank et al. reported in 1989 and 1990 on the extrusion of a number of thermoplastic polymers to produce sustained release pellets.A melt-extrusion process for manufacturing matrix drug delivery systems was reported by Sprockel and coworkers.As one can see, a review of the pharmaceutical scientific literature does not elucidate many applications for hot-melt extrusion in this field. 

Sprockel, O. Sen, M. Shivanand, P. Prapaitrakul, W. A melt-extrusion process for manufacturing matrix drug delivery systems. Int. J. Pharm. 1997,155, 191-199. 

The incorporation of drugs into inert matrices is a popular approach to prolong the drug release. Sustained-release wax matrix drug delivery systems include wax granules or beads prepared by granulation or extrusion/spheronization, tablets, and wax-filled hard gelatin capsules. 

Figure 9.7 Drug release from a planar matrix drug delivery system. The cumulative mass of drug released from a planar drug delivery system as predicted by Equation 9-18 is shown as a function of the rate of diffusion of the dissolved drug in the matrix, Dj.p. The left panel shows release as a function of time and the right panel shows release as a function of the square root of time (with the expected linear dependence). The thickness of the matrix is 1 mm.

Analysis of diffusion-controlled reservoir or matrix drug delivery systems requires a few assumptions ... 

Krogel, I. and Bodmeier, R. (1999) Development of a multifunctional matrix drug delivery system surrounded by an impermeable cylinder, J. Control. Rel 61, 43-50. 

A large variety of drug delivery systems are described in the literature, such as liposomes (Torchilin, 2006), micro and nanoparticles (Kumar, 2000), polymeric micelles (Torchilin, 2006), nanocrystals (Muller et al., 2011), among others. Microparticles are usually classified as microcapsules or microspheres (Figure 8). Microspheres are matrix spherical microparticles where the drug may be located on the surface or dissolved into the matrix. Microcapsules are characterized as spherical particles more than Ipm containing a core substance (aqueous or lipid), normally lipid, and are used to deliver poor soluble molecules... 

One useful drug delivery system is derived from polymers that contain acid-labile linkages in their backbones because hydrolysis rates of such polymers can be readily manipulated by means of acidic or basic excipients physically incorporated into the matrix (2). Further, under certain conditions the hydrolysis of such polymers can be... 

Because these types of polymeric matrix systems are the simplest to design and the easiest to obtain approval by the Food and Drug Administration, they have been the most extensively studied in the past two decades. Numerous polymers have been evaluated for these types of drug delivery systems and although it would be impractical to present each of these polymers and its specific application to drug delivery, this chapter will review in general the types of polymers used as matrices for drug delivery (1-4). 

R. Lipp, H. Laurent, C. Gunther, J. Riedl, P. Esperling, U. Tauber, Prodrugs of Gesto-dene for Matrix-Type Transdermal Drug Delivery Systems , Pharm. Res. 1998,15, 1419 -1424. 

Fig. 2.3 Reservoir- (top) and matrix-based (bottom) drug delivery systems. The matrix system degrades during drug delivery, releasing the drug and matrix through either matrix erosion or degradation.

The inert matrix formulation provided by ethylcellulose and Pevikon (polyvinyl chloride) was an effective vehicle for controlled release drug delivery systems. 

In order to reduce further the ketoprofen release rate from matrix tablets, the partial coating of the cores with CAP was assayed. This technique was successfully applied to obtain a progammable zero-order drug delivery system [5]. 

What was interesting about this study is that it was possible to demonstrate that the sugar was adsorbed onto the internal gelatin particle matrices as well as the visible external particle surface (Table 8.3). This factor needs to be taken into account in any studies on the use of gelatin particles as drug delivery systems, especially if the initial production process is likely to have any influence on the intrinsic characteristics of the matrix. 

For the development of drug delivery systems it is of fundamental importance to achieve the co-precipitation of drugs and biodegradable polymers. The supersaturation working conditions of S AS allow, in many cases, fast and simultaneous precipitation of both polymer and drugs, so that the drugs can be trapped into the polymer matrix. A list of the coprecipitation experimental results is reported in Table 9.9-5. 

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