Controlled Release Silicone Devices

Estrus synchronization therapy requires a specific release rate from silicone devices to maintain the plasmatic level of progestagens between the therapeutic values. Due to this requirement, the initial load of progestagens in the devices is always higher than progestagens solubility in the polymeric matrix. Following are the most important sihcone devices used for the previously mentioned administration of progesterone and norgestomet 

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Nonoxynol-9 is an approved spermicide with strong antiviral activity. A vaginal device which facilitates the controlled release of nonoxynol-9 has been developed for contraceptive and anti-STD purposes. The device, available as a diaphragm or a disk pessary, is fabricated from silicone elastomer matrix system. The drag release profile demonstrates square root time kinetics (M co tV2) (see Section 4.4.2). 

Lee, C. H., Bagdon, R. E., Bhatt, P. P, and Chien, Y. W. (1997), Development of silicone-based barrier devices for controlled delivery of spermicidal agents,/. Controlled Release, 44,43-53. 

One of the most recent developments is the use of microchips as controlled drug delivery devices.[" This novel technology is based on tiny silicon or polymeric chips containing hundreds or thousands of microreservoirs, each of which can be filled with any combination of bioactive agents. In this way. complex release patterns can be achieved with programmed microprocessors. 

The most well known commercial reservoir controlled release systems deliver hormones for contraception from hydrophobic polymers. The Norplant subcutaneous device controls the release of levonorgestrel with silicone rubber, and the Progestasert intrauterine device (lUD) releases progesterone from reservoir devices of ethylene vinyl acetate. In the field of insecticides, reservoir dispensers called BioLure were developed to provide zero-order release ofinsect pheromones to disrupt mating (Smith et al, 1983). The dispenser consists of a slab configuration with a rate-controlling membrane, with constant release described by Eq. 1. 

Controlled release of therapeutics to the specific site over an extended period of time is an important determinant in delivery of active pharmaceutical ingredients. This local delivery reduces potential side effects as well as maximizes therapeutic effects by obtaining the optimal concentration of API in local sites. In recent years, the study of controlled release of API from polymeric devices, which are, e.g., silicone elastomers, has attracted many researchers. Controlled drug delivery applications include sustained delivery over days, weeks, months or years. The application... 

Most studies of the controlled release of drugs from subdermally implanted polymer devices have centered on the use of silicone rubber (Silastic). In 1964 Folkman and Long (3) demonstrated the potential of this polymer for the controlled release of certain cardioactive steroids. The good permeability of silicone rubber to a variety of drugs and its favorable biocompatibility encouraged other workers in its use as membrane material for diffusion controlled delivery devices (4). 

A significant advance in the technique of controlled release will be given by the development of polymer systems which combine the release properties of silicone rubbers with biodegradability. It is immediately obvious that the rate of biodegradation has to be coordinated with the projected life span of the device, i.e., during the release period the release properties of the device should remain essentially unchanged. In the ideal case substantial degradation should commence after depletion of the device. 

Bovine estrus synchronization is an important field for the veterinary pharmaceutical industry. A description of the natural bovine cycle and methods to cycle control are presented. In addition, commercially available silicone devices for bovine estrus synchronization are listed. The mathematical modeling of progestagens release from such devices is a crucial tool in the development of novel and/ or optimized delivery systems. For this purpose, several in vitro models, approaches to explain the ADME processes and overall models are described. This type of mathematical modeling could help in the future to customize drug delivery systems to specific animals and/ or situations. 

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