3.5. Drug Alpelisib ic50 release Kinetics The ability of implants to continuously release drug over extended period of time is crucial especially for glaucoma that requires chronic drug administration. It is highly desirable to avoid erratic drug release with potential implications in therapeutic effectiveness and toxicity. Over-all, biodegradable systems are more prone to nonlinear drug release kinetics and increased Inhibitors,research,lifescience,medical burst effects compared to nonbiodegradable systems [29]. Also, burst release patterns are more pronounced with hydrophilic

drugs in polymer matrices that are usually hydrophobic due to their poor drug-polymer interaction. Considering biodegradable systems, drug release pattern may follow three phases involving initial burst, diffusive release (regulated by polymer degradation rate, surface area, and solubility of loaded drug), and the final burst from Inhibitors,research,lifescience,medical disintegrating polymer matrices [46]. The solubility of the drug determines its loading capacity and the higher the Inhibitors,research,lifescience,medical solubility the more uniform the distribution of drug within the polymer matrix.

Uniform drug distribution further reduces the risk of unwanted burst release [85, 86]. Overloading of drug and nonuniform distribution of drug within the polymer matrix can result in increased release during initial burst, which can cause undesirable ocular effects and inflammatory responses. The release profile of implantable delivery can be affected by the following: (1) amount of drug loaded, (2) surface area and volume of implant, (3) type of polymer and composition, (4) average molecular Inhibitors,research,lifescience,medical weight of polymer, and (5) solubility of the drug. Continuous attempts are being made to minimize the burst effects and achieve linear

drug release kinetics [28, 29]. Formulation Inhibitors,research,lifescience,medical strategies that can enhance drug dispersion in the polymer matrices using suitable drug carriers and emulsifying agents can stabilize the burst effect and result in a drug release rate that correlates with polymer degradation. Also in order to maintain constant release of drug, it is important to use geometrical shapes that will minimize reduction of surface area with Levetiracetam degradation [54]. The various factors that affect drug release rate from ocular implants are summarized in Figure 2. Figure 2 Schematic of the various factors that could affect drug release rate from ocular implants. A viable approach to achieving desired drug release profiles is by modifying the polymer composition. For instance, some studies have demonstrated that combining two PLA monomers of high and low molecular weights resulted in biphasic release pattern (eliminating the final burst) and achieved pseudozero order kinetics comparable to nonbiodegradable systems [29, 48, 87].