Polyanhydrides drug release rates

It has been shown that the crystallinity of polymers affects erosion and drug release rates, because crystalline regions erode slower than amorphous ones. Moreover, highly crystalline polyanhydrides affect the device morphology as it creates irregular external... 

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. 

The SA-FA copolymers displayed nearly constant degradation rates and drug release rates under physiological conditions. The time for complete degradation of poly(fumaric acid) and poly(sebacic acid) oecured in 2 and 15 days, respectively, while their copolymers degraded within this range. Radical copolymerization of styrene and methylmethacrylate with the polyanhydrides resulted in crosslinked insoluble polymers [40]. 

Whether in copolymers or blends, inhomogeneous erosion has a nontrivial effect on drug release kinetics as will be shown later. Leong et al. (1985) demonstrated that the pH of the degradation media also has a dramatic effect on the erosion rate, which increases with increasing pH. The acceleration of degradation of polyanhydrides with increase in pH is widely reported and has been used to speed up experiments (Shakesheff et al., 1994). 

Biodegradable polymer blends of polyanhydrides and polyesters have been used as drug carriers [59], Polyflactic acid) (PLA), polyfhydroxybutyrate) (PHB), and poly(caprolactone) (PCL), of 2000 and 50000 molecular weights were mixed with poly(sebacic anhydride) (PSA), and the properties of these mixtures were studied. Mixtures of PHB and low molecular weight PLA or PCL formed uniform blends with various amounts of PSA. These blends possess different physical and mechanical properties compared to the parent polymers. The release rate of drugs from these polymeric blends increases with the increase in the content of the rapidly degrading component, PSA. 

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