Matrix delivery systems

With this diffusion coefficient, assuming a 100-/rm thick membrane, the characteristic diffusion time is 10 days t = L 2j2D). 

1 Matrix Delivery Systems with Dissolved Drugs 

Desorption of Dispersed Drug from a Slab. The release of a drug that is initially dissolved within a polymer matrix can be predicted by solving the equations for drug diffusion within the polymer slab  

The total amount of drug released from the matrix can be determined by integration  

For the early stages of release (M, 0.6M, this expression is closely approximated by  

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Thus, the amount of drug released is proportional to the square root oftjiBe ndCs. In some cases, diffusion is not the only pathway by which a drug is released from the delivery system. The erosion of the delivery matrix following relaxation of the polymer and other functional excipient(s) contributes to the overall drug release as well. Discussed below are examples of the diffusion- and erosion-controlled matrix delivery systems. 

Polygel matrix delivery system Stealth liposome Liposome Reservoir insert... 

Figure 9.6 Schematic of matrix-type systems for controlled drug delivery. Matrix delivery systems can be constructed with drug dissolved in the matrix material (a) or particles of drug dispersed to form a composite material (b and c). For dispersed drug particles, the overall loading is an important determinant of the dynamics of release.

Matrix Delivery Systems for Water-soluble Drugs and Proteins... 

The typical release profiles shown in Figure 32.4 for reservoir and matrix delivery systems may present variations a burst effect due to the presence of some core material too close to the external device surface for matrix devices, or a delayed time to start diffusion due to the diffusion of the core through the encapsulating layer of the reservoir device. Also, the physical state of the core material (dissolved or dispersed) defines the release kinetics. For example, a reservoir system in which the active core is not dissolved results in zero-order kinetics (constant flow), whereas it results in first-order kinetics (exponentially decreasing flow) if the core is dissolved in the encapsulated material. 

Kent, J., Cholesterol matrix delivery system for sustained release of macromolecules, U.S. Patent4,452,775, June 5, 1984. 

Diffusion. Diffusional dmg delivery systems utilize the physicochemical energy resulting from concentration differentials. Dmg molecules diffuse through a polymer matrix or through a polymer membrane film from a region of high concentration to one of low concentration. 

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... 

United States Patent 4,767,628 assigned to Imperial Chemical Industries describes a similar lactide/glycolide delivery system for LHRH polypeptide (122,123). A multiphase release pattern is again postulated. The first phase occurs by diffusion of drug through aqueous polypeptide domains linked to the exterior surface of the matrix. 

A unique method of formulating delivery systems based on starch/ PLA systems was studied (138). In that approach, the goal was to provide a better matrix for delivery of high molecular weight hydrophilic molecules. A hydrophilic material, starch, was combined through graft polymerization to PLA. The carbolactic polymers were then used to entrap bovine serum albumin in microspheres. 

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... 

Recently, water-soluble protein fractions, isolated from extracts of bone matrix, were incorporated into a collagen matrix and shown to induce bone (67,68) and cartilage formation both in vitro and in vivo (69,70). In the latter studies, in the absence of the collajgen delivery system, the proteins were incapable of inducing cartilage formation in vivo when implanted intramuscularly into mice. The success of this approach appears to depend on delivering the active agents at an effective dose over an extended time period. 

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.

Because dinoprostone produces cervical ripening along with stimulation of the uterus, it has been used as an alternative to oxytocin for the induction of labor. Preparations of dinoprostone can be placed in either the cervix or the posterior fornix. Prepidil is a formulation and delivery system of dinoprostone that delivers a dose of 0.5 mg into the cervix, while Cervidil consists of the drug embedded in a plastic matrix. The matrix is designed to deliver a dose of 0.3 mg per hour for 12 hours. 

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