Design and manufacture of microparticles containing small molecules or biologics for optimized drug release

Oral delivery is the preferred and the most common route of drug administration. This thesis describes the development of innovative oral formulations to overcome poor drug bioavailability, which is currently one of the major challenges in the area of the pharmaceutical research. Microparticles (MPs) were employed to improve the bioavailability of orally administered APIs, differing both from physicochemical properties and therapeutic purposes. Case studies I-II: MPs based on hydrophilic carriers, called Gelucires, successfully improved the oral bioavailability of poorly water soluble drugs. The bioavailability enhancement of Gelucires-based MPs relied on multiple mechanisms, including improved wettability, micelle formation and effects resulting from changes in the drug crystalline state, specifically amorphisation, conversions into metastable polymorphs and crystals size reduction. Case study III: MPs were successfully employed for the oral local delivery of an active compound for the treatment of IBD. In this case, an approach based on the encapsulation of nanoparticles into enteric polymeric MPs was adopted. The application of responsive materials allowed to achieve a selective drug delivery to the inflamed sites with limited systemic absorption. Case study IV-V-VI: solid lipid microparticles (SLMs) were explored as strategy for the local oral delivery of biologic drugs, specifically an enzyme and a peptide. In the development of oral biotherapeutics, one of the most challenging tasks to overcome is the loss of biological activity due to physical and chemical instabilities. SLMs protected the active compounds from the gastric degradation and released them closer to the target site by exploiting the action of bile salts and physiological lipases, which emulsified and degraded the lipid matrix promoting the drug release. Concluding, MPs can provide a solid platform for the development of oral formulations, representing a versatile drug delivery system able to address the different issues related to poor oral bioavailability.