Polyanhydrides controlled release devices

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. 

Polyanhydrides have been investigated as a candidate for controlled release devices of drugs for treating eye disorders (93), chemotherapeutic agents (94,95),... 

E.-S. Park, M. Maniar, J. Shah, Effects of model compounds with varying physicochemical properties on erosion of polyanhydride devices, J. Control. Release 40 (1996) 111-121. 

A much more desirable erosion mechanism is surface erosion, where hydrolysis is confined to a narrow zone at the periphery of the device. Then, if the drug is weU-immobihzed in the matrix so that drug release due to diffusion is minimal, the release rate is completely controlled by polymer erosion, and an ability to control erosion rate would translate into an ability to control dmg delivery rate. For a polymer matrix that is very hydrophobic so that water penetration is limited to the surface (thus Hmiting bulk erosion), and at the same time, allowing polymer hydrolysis to proceed rapidly, it should be possible to achieve a drug release rate that is controlled by the rate of surface erosion. Two classes of biodegradable polymers successfully developed based on this rationale are the polyanhydrides [31] and poly (ortho esters) [32], the latter of which is the subject of this chapter. 

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