Polyanhydrides degradation kinetics

Modeling the behavior of bioerodible polyanhydrides is complicated by the many phenomena contributing to release profiles described in the previous section. The degradation kinetics may be coupled to other processes, such as diffusion and dissolution, and the overall erosion kinetics represent the sum of all of these multiple processes (Goepferich, 1996a). 

Figure 5 General structure of polyanhydrides. R and R can be varied to modify degradation kinetics and profile. The lower frame shows the structure of P(CPP-SA), a polyanhydride copolymer, used in the Gliadel product. Abbreviations SA, sebacic acid CPP, carboxyphen-oxypropane.

The in vitro degradation and drug release of polyanhydride formulations is not necessarily equivalent to the in vivo kinetics. For information on the in vivo kinetics, the interested reader is referred to the recent review by Katti et al. (2002) and the review by Domb et al. (1997). 

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). 

Polyanhydrides because of their surface erosion properties can be ideal materials for a constant rate release profile (a zero order). Furthermore, these polyanhydrides are very hydrophobic and their hydrolytic degradation may take relatively a long time, which is not suitable for pulsatile release. Hence, in order to achieve a tunable erosion kinetics, a two-component polyanhydride made of SA precursor and CPP precursor when copolymerized with polyethylene glycol (PEG) was found to retain the surface erosion of two-component polyanhydride while increasing the erosion rate due to inaeased hydrophilicity by PEG functionality. Relatively faster erosion rates can be achieved by adjusting PEG precursor content [37]. 

Polyorthoesters are a third class of biodegradable polymers that have been extensively investigated for dmg delivery applications.The degradable orthoester linkage is composed of a carbon bonded to three alkoxy groups. Polyorthoesters are generally more hydrophobic than polyesters and polyanhydrides, due to their lack of carbonyl functionality, and the intrinsic hydrolysis kinetics of the orthoester linkage is comparable to that of an anhydride. Polyorthoesters, therefore. 

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