10.3.8  “In Vitro” Release Studies

Drug release studies are critical in the development of drug delivery systems and allow calculating the amount of microparticles to be injected. Release rate assays are carried out in “sink conditions” to avoid solubility problems that can affect the drug release rate behavior. Particles can be suspended in the release medium directly or separated by a cellophane membrane. In the latter case, larger volumes of attack medium are employed.

Generally, microparticles are suspended in a volume of an aqueous solvent and placed in a shaker bath with constant agitation and at 37°C. At fixed time intervals, the supernatant is removed and drug concentration is quantified. The same volume of fresh medium is replaced to continue the release study (Herrero-Vanrell and Refojo 2001). The attack medium can contain Tween 80 (0.02%) and/or sodium azide (0.05%) (Checa-Casalengua et al. 2011).

Release rate of active substances from microparticles involves several mechanisms: diffusion through the polymer matrix and/or through the fluid-filled pores present in the particles, physical erosion and/or hydrolysis of the polymer, ion exchange, or several of these mechanisms (Li 1999; Herrero-Vanrell and Refojo 2001).

The release kinetic of the drug is a function of the polymer structure, molecular weight and rate of degradation in the case of bioerodible polymers, the physicochemical properties of the drug (mainly solubility and molecular size), drug loading,­

size of the particles, and the microencapsulation technique. Usually, the encapsulated drug is released according to a first order kinetic in which the release rate is a function of the concentration of the substrate. Low molecular weight biodegradable polymers release the encapsulated drug faster than high molecular weight ones. In its turn, higher size microparticles, with lower surface area, release the active substance slower than low size particles (Fig. 10.8).

10.3.8.1  Additives in Microspheres

Drug release profile from microparticles can be modulated to some extent by modifying their components. If the solvent evaporation technique is used to prepare microspheres, additives can be added to the inner or the external phase of the emulsion (Herrero-Vanrell and Refojo 2001; Martinez-Sancho et al. 2003a, b; HerreroVanrell and Molina 2007). If the additive is incorporated in the inner phase of the emulsion it remains in the microparticles. In such cases the additive must be biocompatible and biodegradable (Barcia et al. 2005). Additives can promote higher drug encapsulation efficiencies and longer release rate compared with the microspheres without additive (Martinez Sancho et al. 2003a) (Fig. 10.9).