Rate-controlling polymers

A typical reservoir system consists of a core (the reservoir) and a coating membrane (the diffusion barrier). The core contains the active ingredients and excipients, whereas the membrane is made primarily of rate-controlling polymer(s). The governing release mechanism is diffusion from the reservoir across the membrane to the bulk solution, and the one-dimensional release rate is described by Eqs. (4.4), (4.17), and (4.22).10,14 In addition,... 

Diffusion-controlled membranes exist in two categories depot systems, in which the drug is totally encapsulated within a reservoir, and monolithic systems, where the drug is dispersed in a rate-controlling polymer matrix [25]. One commercially successful depot device is the Alza Ocusert for ocular delivery of pilocarpine in the treatment of glaucoma [25]. 

The reservoir patch has a similar bioadhesive component but pharmaceutical formulations containing certain excipients, such as penetration enhancers and enzyme inhibitors, can be placed in the center of the design. A rate-controlling polymer membrane can be designed to control the drag release. 

The types of systems that can be produced using micelle formation include spheres, shells, capsules, vesicles, clusters, and particles of various shapes and sizes, such as spheres, rods, planar structures, and layered structures. Further processing can be undertaken to add rate-controlling polymer membranes to the outer shell and to incorporate different molecules to the surface (e.g., for receptor recognition). 

DL Theis, LJ Lucisano, GW Halstead. Use of stable isotopes for evaluation of drug delivery systems Comparison of ibuprofen release in vivo and in vitro from two biphasic release formulations utilizing different rate-controlling polymers. Pharm Res 11 1069—1076,1994. 

As shown in this chapter, formulating HPMC matrices can be a complex process critical factors being drug solubility, dosage level, rate-controlling polymer and excipient choice. In order to help the pharmaceutical scientists with a starting formula for hydrophilic matrix tablets, Colorcon, hic. has developed a predictive formulation service called HyperStart [97]. This system is based on mathematical models and relationships, validated with extensive experimental data. Use of the HyperStart formulation service may help to simplify the formulation and development process and reduce the time to market. 

Particularly useful rate-controlling polymers for causing an effective controlled release of administered drug or agent following the administration are summarized in Table 8.3. 

The polyelectrolyte covalently functionalized with reactive groups may be viewed as an enzyme-like functional polymer or as a molecular reaction system in the sense that it has both reactive centers and reaction rate-controlling microenvironments bound together on the same macromolecule. 

The reactivity modification or the reaction rate control of functional groups covalently bound to a polyelectrolyte is critically dependent on the strength of the electrostatic potential at the boundary between the polymer skeleton and the water phase ( molecular surface ). This dependence is due to the covalent bonding of the functional groups which fixes the reaction sites to the molecular surface of the polyelectrolyte. Thus, the surface potential of the polyion plays a decisive role in the quantitative interpretation of the reactivity modification on the molecular surface. 

Most radicals are transient species. They (e.%. 1-10) decay by self-reaction with rates at or close to the diffusion-controlled limit (Section 1.4). This situation also pertains in conventional radical polymerization. Certain radicals, however, have thermodynamic stability, kinetic stability (persistence) or both that is conferred by appropriate substitution. Some well-known examples of stable radicals are diphenylpicrylhydrazyl (DPPH), nitroxides such as 2,2,6,6-tetramethylpiperidin-A -oxyl (TEMPO), triphenylniethyl radical (13) and galvinoxyl (14). Some examples of carbon-centered radicals which are persistent but which do not have intrinsic thermodynamic stability are shown in Section 1.4.3.2. These radicals (DPPH, TEMPO, 13, 14) are comparatively stable in isolation as solids or in solution and either do not react or react very slowly with compounds usually thought of as substrates for radical reactions. They may, nonetheless, react with less stable radicals at close to diffusion controlled rates. In polymer synthesis these species find use as inhibitors (to stabilize monomers against polymerization or to quench radical reactions - Section 5,3.1) and as reversible termination agents (in living radical polymerization - Section 9.3). 

The polymerization rate is controlled by the slowest process. Thus it is important to establish the rate controlling steps. The starting material for the (SPP) can be the dry nylonsalt Z 4) but mostly a low or middle molecular weight polymer is used. The polyamide-salts have the disadvantage of high amine losses 3 4). 

FIGURE 14 In vitro rate of release of testosterone from a PCL capsule (reservoir device), illustrating rate control by drug dissolution when the polymer membrane thickness is small. (From Ref. 68.)... 

When acidic or latent acidic excipients (anhydrides) are incorporated into the polymer to control erosion rate, the polymers become quite sensitive to moisture and heat and must be processed in a dry environment. A rigorous exclusion of moisture is particularly important with materials that are designed to erode in less than 24 hr. Such materials may contain up to 5 wt% of an acidic catalyst and are analogous to a "loaded gun" in that even the slightest amount of moisture will initiate hydrolysis at the elevated processing temperatures. ... 

It has been demonstrated that a variety of different polyphosphazenes can be developed as biomaterials, membranes or hydrogels, bioactive polymers, and bioerodible polymers. As with most new areas of polymer chemistry and biomaterials science, molecular design forms the basis of most new advances, but the rate-controlling step is the testing and evaluation of the materials in both in vitro and in vivo environments. This is particularly true for polyphosphazenes where the availability of research quantities only has limited the... 

Although many different processes can control the observed swelling kinetics, in most cases the rate at which the network expands in response to the penetration of the solvent is rate-controlling. This response can be dominated by either diffu-sional or relaxational processes. The random Brownian motion of solvent molecules and polymer chains down their chemical potential gradients causes diffusion of the solvent into the polymer and simultaneous migration of the polymer chains into the solvent. This is a mutual diffusion process, involving motion of both the polymer chains and solvent. Thus the observed mutual diffusion coefficient for this process is a property of both the polymer and the solvent. The relaxational processes are related to the response of the polymer to the stresses imposed upon it by the invading solvent molecules. This relaxation rate can be related to the viscoelastic properties of the dry polymer and the plasticization efficiency of the solvent [128,129],... 

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