Controlled Microparticles - A PAT Strategy for Microparticle Production Processes

In many pharmaceutical products microparticles are used as carrier for APIs (Active Pharmaceutical Ingredients). The microparticles are usually embedded in other structures (compressed or granulated) or they are filled directly into a gelatine capsule. The release behaviour of the API from these particles is an important aspect for the action of the drug. The temporal profile and the uniformity of the release profile depend on the microparticle structure, which is a function of the synthesis process. There are many different kinds of particle synthesis, for example flow-induced phase inversion or rapid expansion methods. Another common approach is the emulsification method. First of all an emulsion of fluid drops is produced and it is then transformed into a particle suspension trough a precipitation- or hardening step. The disadvantage and weakness of this method is that the produced microparticles typically have a polydisperse size spectrum. Another disadvantage is the residual content of the solvent, which is absolutely unwanted. Essential for the whole production process is a precise control of the emulsification/hardening step. The goal of this project is to develop a robust and scalable microparticle production process on the basis of the emulsification/hardening principle. This process should produce microparticles with a defined (and close) size distribution, as well as a defined repartition of the API inside the granules, with the result of a controlled drug release. With the "Process Analytical Technology (PAT) initiative of the US-American Food and Drug Administration (FDA), as well as the very broad overall concept of "Quality by Design", a new concept for manufacturing pharmaceutical products for the pharmaceutical industry is invented. The subject of this project is the application of this concept to the issue of microparticle formation.