Controlled-release devices

Polylactic acid (PLA) has been produced for many years as a high-value material for use in medical applications such as dissolvable stitches and controlled release devices, because of the high production costs. The very low toxicity and biodegradability within the body made PLA the polymer of choice for such applications. In theory PLA should be relatively simple to produce by simple condensation polymerization of lactic acid. Unfortunately, in practice, a competing depolymerization process takes place to produce the cyclic lactide (Scheme 6.10). As the degree of polymerization increases the rate slows down until the rates of depolymerization and polymerization are the same. This equilibrium is achieved before commercially useful molecular weights of PLA have been formed. 

Here we might note that cobalt(II) hydroxide, but not the oxide, also forms cements (Allen et al., 1984 Mansion Gleed, 1985 Prosser et al., 1986). It also is used in controlled-release devices for supplying trace elements to cattle and sheep. Nothing is known of its structure. 

Initial tests in the rat revealed a high degree of tissue compatibility of Dat-Tyr-Hex derived polymers. More detailed tests are now in progress. In addition, tyrosine derived polymers are currently being evaluated in the formulation of an intracranial controlled release device for the release of dopamine, in the design of an intraarterial stent (to prevent the restenosis of coronary arteries after balloon angioplasty), and in the development of orthopedic implants. The use of tyrosine derived polymers in these applications will provide additional data on the biocompatibility of these polymers. 

Sustained- and controlled-release devices for drug delivery in the vaginal and uterine areas are most often for the delivery of contraceptive steroid hormones. The advantages in administration by this route—prolonged release, minimal systemic side effects, and an increase in bioavailability—allow for less total drug than with an oral dose. First-pass metabolism that inactivates many steroid hormones can be avoided [183,184],... 

Reithmeier, H., Herrmann, J., and Gopferich, A., Lipid microparticles as a parenteral controlled release device for peptides, Journal of Controlled Release, 2001, 73, 339-350. 

The encapsulation and release of l,3-bis(2-chloroethyl)nitrosourea (BCNU) in P(CPP-SA) 20 80 wafers was the first implantable controlled release device based on polyanhydrides that was FDA-approved and marketed (Gliadel ) (Chasin et al., 1988). BCNU was encapsulated by two techniques, trituration and co-dissolution, resulting in different release profiles (Chasin et al., 1990, 1991). The triturated samples released faster than those prepared by co-dissolution, presumably due to more homogeneous loading in the samples prepared by co-dissolution. 

This contribution will provide a review of polylectrolytes as biomaterials, with emphasis on recent developments. The first section will provide an overview of methods of synthesizing polyelectrolytes in the structures that are most commonly employed for biomedical applications linear polymers, crosslinked networks, and polymer grafts. In the remaining sections, the salient features of polyelectrolyte thermodynamics and the applications of polyelectrolytes for dental adhesives and restoratives, controlled release devices, polymeric drugs, prodrugs, or adjuvants, and biocompatibilizers will be discussed. These topics have been reviewed in the past, therefore previous reviews are cited and only the recent developments are considered here. 

We described reservoir capacity as the ability to contain an active ingredient within a matrix. In this sense, we give the term active ingredient the broadest possible meaning. We will show how polyurethanes are used to absorb exudates from deep tissue wounds. The exudates are considered active ingredients. We likened reservoir capacity to a bottle and controlled release to a bottle with a leak. A polyurethane can serve as a controlled release device, and we will illustrate this in a number of applications. 

J.A.H. van Laarhoven, M.A.B. Kruft, and H. Vromans, Effect of supersaturation and crystallization phenomena on the release properties of a controlled release device based on eva copolymer, J. Controlled Release, 82(2-3) 309-317, August 2002. 

Functionalized polymers are of interest in a variety of applications including but not limited to fire retardants, selective sorption resins, chromatography media, controlled release devices and phase transfer catalysts. This research has been conducted in an effort to functionalize a polymer with a variety of different reactive sites for use in membrane applications. These membranes are to be used for the specific separation and removal of metal ions of interest. A porous support was used to obtain membranes of a specified thickness with the desired mechanical stability. The monomer employed in this study was vinylbenzyl chloride, and it was lightly crosslinked with divinylbenzene in a photopolymerization. Specific ligands incorporated into the membrane film include dimethyl phosphonate esters, isopropyl phosphonate esters, phosphonic acid, and triethyl ammonium chloride groups. Most of the functionalization reactions were conducted with the solid membrane and liquid reactants, however, the vinylbenzyl chloride monomer was transformed to vinylbenzyl triethyl ammonium chloride prior to polymerization in some cases. The reaction conditions and analysis tools for uniformly derivatizing the crosslinked vinylbenzyl chloride / divinyl benzene films are presented in detail. 

Poly(vinylbenzyl chloride) (VBC) is an ideal starting material onto which a variety of functional groups can be attached through relatively simple reactions and mild reaction conditions. Functionalized polymers are of interest in a variety of applications including but not limited to fire retardants, selective sorption resins, chromatography media, controlled release devices and phase transfer catalysts. An example of the wide applicability of functionalized polymers is provided by trimethyl ammonium functionalized poly(VBC). 

As a consequence of metered, localized drug delivery, controlled release devices generally equal or improve the therapeutic effects of conventional medications, while using a fraction of the drug. Thus, the problems of drug-related side effects are correspondingly lower. 

Many controlled release devices are not membranes by the conventional definition, since only transient release of an active agent, without permeation occurring between an upstream and a downstream, is typical. Nevertheless, some controlled release units do operate with a concentration driving force to achieve effectively steady state release from the internal reservoir of the device to the external surrounding. Such processes are included here for completeness. 

The controlled release device consists of a thin drug formulation-agarose gel supported on an impermeable backing material. A number... 

WANGETAL. Disposable Controlled-Release Device for Drug Infusion... 

The methodology developed to date has led to a marked improvement in the accuracy with which release rates can be measured from hollow fiber formulations. A careful combination of methods such as the combined use of the airflow and extraction methods discussed here with the appropriate combination of quantification methods will ultimately lead to a better understanding of the various factors affecting the release of materials from controlled release devices. 

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