Control of Drug Release from Microparticles by Tuning Their Crystalline Textures: A Structure–Activity Study

Predicting drug release profiles from polymer microparticles has proven challenging due to the numerous environmental and chemical factors that affect the device and influence the rate of drug release. By measuring the various polymer properties that can influence drug release, a predictive approach can be used to select polymers with specific properties that will lead to the desired release profile for the application. To illustrate this, a library of tyrosol-derived poly­(ester-arylate)­s, poly­(amide)­s, and poly­(carbonate)­s were used to evaluate the effects of physical (crystallinity, water accessibility, thermal, and hydrophobicity) and chemical (polymer–drug interactions) polymer properties on the release of a highly crystalline drug dexamethasone, which was loaded at a high weight percent (wt %) in microparticles. Nuclear magnetic resonance (NMR) experiments showed that the polymer and drug were not chemically interacting and instead exist as a physical mixture even after exposure to physiological conditions. Polymer crystallinity data revealed that crystallite size was strongly correlated with faster drug release, suggesting that larger crystallites reduce the tortuosity for dexamethasone to diffuse out of the particle matrix. This correlation observed in particles with and without the drug was reproduced with bulk polymers, indicating that crystallinity data from bulk polymers can be used to predict release profiles without having to prepare drug-loaded particles. Consistent with the crystallinity data, particle pore sizes of representative formulations showed that particles with larger pores resulted in faster dexamethasone release. Interestingly, thermal properties (glass transition temperature and melting temperature), polymer hydrophobicity, and molecular weight retention at the end of the 119-day release study did not show any correlation with drug release.