(Herrero-Vanrell and Refojo 2001; Grizzi et al. 1995) and the type and amount of drug contained in the formulation are also critical. Acidic and basic drugs encapsulated in microparticles might enhance the hydrolytic degradation of PLA and PLGA polymers (Maulding et al. 1991; Delgado et al. 1996; Li 1999). Beck et al. (1983) studied the biodegradation of DL-PLGA microcapsules loaded with norethisterone and observed a faster biodegradation of the microcapsules as the ratio of glycolide in the copolymers increases. On the other hand, Delgado et al. (1996) reported that drug released from the microspheres was higher when the molecular weight of the polymer or the amount of the encapsulated drug increases. The reported data suggest that the presence of drug, as reported by other authors, may affect degradation time of the polymer (Visscher et al. 1985; Maulding et al. 1991).

Vitrectomy is an important issue regarding to microparticle clearance. Moritera et al. (1991) reported the degradation of PLA microspheres loaded with 5FU after intravitreal administration. Particles gradually become smaller and finally disappeared from the normal rabbit vitreous in 48 ± 5.2 days. However, the clearance from the vitreous cavity was accelerated to 14 ± 2.4 days in the eyes that had undergone vitrectomy. On the other hand, when Giordano et al. (1995) evaluated the biodegradation and clearance time of unloaded PLGA microspheres of a relatively low molecular weight (inherent viscosity 0.2 dl/g) from the vitreous cavity in rabbits after gas vitrectomy, they found evidence of the microparticles up to 24 weeks postinjection (Giordano et al. 1995).

Other factors that affect the rate of degradation of microspheres after intravitreal injection are the amount and the size (total surface area) of the microspheres injected, the properties of the polymer (polymer crystallinity, lactic acid and glycolic acid ratio and molecular weight). For example, the amorphous 50:50 PLGA has shorter half-life than the 75:25 PLGA, and this one shorter than the crystalline PLA (Li 1999).

For the same polymer composition, the lower molecular weight is the faster is the degradation time. Smaller size microparticles degrade faster than larger sizes (Grizzi et al. 1995).

10.8  In Vitro and In Vivo Correlation

There are many published examples of drugs with dissolution data that correlate well with drug absorption in the body in the oral route. These studies are not so frequent for the intraocular route. Good correlations between in vitro and in vivo data of the released drug resulted useful to understand the in vivo behaviour of a drug delivery system.

He et al. (2006) injected 0.1 ml containing 10 mg of PLGA (75:25) microspheres loaded with cyclosporine in rabbits. Cyclosporine was quantified from samples of blood, aqueous humor, conjunctiva, iris/ciliary body, sclera, lens, vitreous, and retina\choroids. A good correlation was observed between in vivo AUCt\AUC65 (area under the drug concentration vs. time points for the total period of 65 days) expressed in percentage for retina and choroids and the in vitro cumulative release percent (%) for the corresponding time points (up to 65 days).