Sustained-release device

This chapter is devoted to a miscellaneous group of aqueous acid-base cements that do not fit into other categories. There are numerous cements in this group. Although many are of little practical interest, some are of theoretical interest, while others have considerable potential as sustained-release devices and biomedical materials. Deserving of special mention as biomedical materials of the future are the recently invented polyelectrolyte cements based on poly(vinylphosphonic adds), which are related both to the orthophosphoric acid and poly(alkenoic add) cements. 

Fig. 15 Drawing showing the optimum placement of an intravitreal sustained-release device in the eye. (From Ref. 224.)...

The use of intravitreal ciclosporin sustained-release devices to manage ERU has been reported (Gilger Allen 1998, Gilger et al 2000). These are placed via sclerotomy performed under general anesthesia implants delivering 4p,g/day have shown significant therapeutic potential. However, preexisting cataracts are a contraindication of this t)qje of therapy and care is required in case selection. 

Nonimmediate- or sustained-release devices can be divided into two categories. The first is a reservoir device whereby the dmg is loaded into the reservoir as either a solid or a liquid. Dmg release occurs by diffusion through either a semipermeable membrane or a small orifice. Lasers are commonly used to generate uniform orifices through which the dmg will diffuse. Osmotic pressure is commonly used to provide the driving force for dmg dispersion. The second is a matrix diffusion device whereby the dmg is dispersed evenly in a solid matrix. Polymers are commonly used as the matrix. Dmg delivery is accomplished by either dissolution of the matrix, with corresponding release of dmg, or diffusion of the dmg from the insoluble matrix. 

The physicochemical properties of the drug are critical in the design of the dosage form. Solubility, stability, and pH can strongly affect whether a drug can be delivered effectively from a controlled delivery device. Because sustained-release devices often contain multiple doses that if released immediately would reach toxic levels, the physicochemical properties and formulation process may have to be more tightly controlled compared with immediate-release systems. 

Another approach has been the use of solid, sustained release devices that are injected or surgically implanted and which slowly release the drug. These systems can, in general, be classified as either membrane-controlled or matrix-controlled. 

Optimal steroid therapy for PVR would maintain therapeutic levels in the vitreous for a prolonged period at present this can only be achieved by prohibitively high systemic dosing or intravitreal injections (which do not maintain constant drug levels). A sustained release device that maintains constant therapeutic intravitreal levels with minimal systemic exposure may prove useful in the clinical management of PVR, although the potential for ocular effects such as elevation of intraocular pressure and cataract cannot be ignored. 

IMPLANTED NONDEGRADABLE SUSTAINED-RELEASE DEVICES Description of Drug Delivery System... 

A rabbit model to assess the possible neuroprotective effects of central acting calcium channel blockers using a nondegradable sustained-release device has been developed (3). In this model an intraocular infusion was used to elevate the intraocular pressure (IOP). To assess the effects of the study drug, IOP was maintained at 40mmHg for over an hour in both treatment and control eyes and was then decreased to a normal level. The procedure was repeated at 48 and 72 hours to simulate IOP spikes in human eyes (3). 

Figure 6 ERG B-wave amplitude ratios (drug device implanted eye/fellow eye) in normal rabbit eyes with a fluocinolone acetonide sustained-release device in one eye. The dark adapted B-wave amplitude ratio was initially slightly greater than one during the first three weeks of the study. Thereafter, levels remained near one for more than one year after device implantation. At 28 weeks, the B-wave amplitude ratio was lower than at other time points (approximately 0.75 P<0.05) however, by 54 weeks the ratio (0.89) was once again not significantly different from 1 (P = 0.17). Abbreviation ERG, electroretinography.

A sustained-release device containing cyclosporin A has been evaluated in a rabbit model of experimental uveitis (6). The model has been described earlier and involved initial subcutaneous immunization of the rabbits followed by an intravitreal... 

Figure 7 Histological sections of a normal rabbit eye that received a 15mg fluocinolone acetonide sustained-release device demonstrated normal uveal anatomy. (A) Iris and ciliary body (hematoxylin and eosin xl2). (B) Retina in the region of the medullary ray. There is an artifactual retinal detachment (hematoxylin and eosin x40). (C) High-power view of B (hematoxylin and eosin x 100).

Figure 10 Diagram showing three methods of wound closure after insertion of a ganciclovir sustained-release device. (A) Wound closure with an X suture on either side of the anchoring suture. Note that the X suture is started within the wound so that the knot remains buried when the suture ends are trimmed. The long ends of the anchoring suture are placed under the two X sutures. (B, C) Wound closures with a running suture. Note that the suture is started within the wound so that the knot remains buried when the suture ends are trimmed. The long ends of the anchoring suture are placed under the running suture.

Velez G, Robinson MR, Durbin T, Yuan P, Sung C, Whitcup SM. Thalidomide sustained release devices for choroidal neovascularization an in-vitro analysis. Invest Ophthalmol Vis Sci 1999 40 S84 (Abstract no 448). 

Figure 4 Photograph of a Posurdex, a biodegradable dexamethasone sustained-release device which is inserted into the posterior segment.

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