Nondegradable devices

Thus a reservoir system can provide constant release with time (zero-order release kinetics) whereas a matrix system provides decreasing release with time (square root of time-release kinetics). A summary of the drag release properties of reservoir and matrix nondegradable devices in given in Table 4.3. 

A rabbit model of uveitis has been used to test nondegradable devices containing dexamethasone, fluocinolone acetonide, cyclosporin A, and a combination of... 

Figure 2 Diagram of an ocular nondegradable device with a reservoir design. The central drug core is surrounded by an impermeable nondegradable layer (dark gray) which is surrounded by an outermost semipermeable nondegradable layer (light gray).

While a number of animal models of diabetic macular edema exist, sustained delivery of steroids using a nondegradable device has not been tested in an animal model (14,15). Other nondegradable sustained-release drugs that have been investigated in vitro but not in animal models, include methotrexate and trimetrexate to treat intraocular lymphoma, and disease 2-methoxyestradiol to treat choroidal neovascularization (16 18). 

Figure 4 Fluocinolone acetonide release rates after nondegradable devices containing 2mg drug were placed in PBS (open circles), then switched back to PBS with 50% plasma proteins closed circles), and then switched back to PBS (open triangles), n — 8 at each time point. Data represent mean standard deviation. First arrow denotes time at which devices were switched from PBS to PBS + plasma protein. Second arrow refers to time at which devices switched back to PBS alone. Abbreviation. PBS, phosphate-buffered saline.

However, complications particularly associated with removal of nondegradable devices include loss of the device into the vitreous cavity, separation of the pellet from the support strut, vitreous hemorrhage, particularly with repeated same site exchanges, and thinning of the sclera resulting in wound leakage... 

Nondegradable Devices. The popularity of matrix systems can be attributed to the simplicity of either diffusing the drug into the substrate or mixing it in the polymer and/or solution before making the device. 

Since poly(L-tyrosine) cannot be processed into shaped devices, compressed pellets rather than solvent cast films were used as control implants. Poly(L-tyrosine) formed strikingly yellow, moderately inflamed patches that remained at the implantation site throughout the 1-year study. Contrary to soluble proteins or peptides that ar rapidly degraded by enzymes, implants of conventional poly(L-tyro-sine) were evidently nondegradable over a 1-year period. At wee 56 all poly(L-tyrosine) implants were infiltrated by a moderate n ber of inflammatory cells. 

Table 4.3 A summary of the drag release properties of reservoir and matrix nondegradable implant devices...

Figure 4.8 Drug release by diffusion through a nondegradable polymeric matrix. There is a decrease in the release rate from the device with time...

Vibratory-Conveyor Devices Figure 11-62 shows the various adaptations of vibratory material-handling equipment for indirect heat-transfer service on divided solids. The basic vibratory-equipment data are given in Sec. 21. These indirect heat-transfer adaptations feature simplicity, nonhazardous construction, nondegradation, nondusting, no wear, ready conveying-rate variation [1.5 to 4.5 m/min (5 to 15 ft/min)], and good heat-transfer coefficient—115 W/(m -°C)... 

Nondegradable polymers. These are stable in biological systems. They are mostly used as components of implantable devices for drug delivery. 

Nondegradable Intraocular Sustained-Release Drug Delivery Devices... 

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). 

After three and six weeks, implants in gas-filled eyes had smaller amounts of drug than implants in eyes without gas. The authors hypothesized that this discrepancy was due to an increased drug clearance rate in gas-filled eyes secondary to transient disruption of the blood-retinal barrier caused by the intravitreal injection of C3F8 gas. Maintenance of the steady-state level would then require a higher rate of drug release from implants in the gas-filled eyes. If this hypothesis is true then nondegradable sustained-release drug devices may have a shorter lifespan in gas-filled eyes (27). 

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