Laurin Zöller

ESR8: Predicting the dissolution gains and precipitation risks of salt and co-crystal forms of drugs

AstraZeneca, Sweden, (AZ)

Supervisor: Eva Karlsson & Sara Carlert (AZ)

Planned secondments: JWGU (Kostewitz) (Purpose: Transfer model testing and PBPK modelling, PhD courses.)

Project Description

Different in vitro dissolution models have been established for the evaluation of salts, including one compartment and multi compartment models mimicking the in vivo pH changes along the GI tract. Some models also include absorption compartments to regulate the supersaturation levels. Additional parameters such as importance of buffer capacity and hydrodynamics has not been extensively evaluated in the dissolution of salts. Combinations of in vitro dissolution, supersaturation and precipitation and in silico physiologically based biopharmaceutical model (PBBM) has been described in the literature, but a mechanistic salt model is currently lacking in existing commercial in silico tools. AstraZeneca has developed a prototype in silico model, which remains to be validated. This model describes how a layer of precipitated free form on the salt particle may alter the salt dissolution and decrease the apparent solubility. The current project will involve evaluation of this model together with the use of different in vitro dissolution techniques for salt dissolution.

Background

During my biochemistry studies at University of Bayreuth, I learned the basics of organic, physical and inorganic chemistry. I was particularly enthusiastic about the synthesis of physiologically active substances, their optimization and their pharmaceutical tests as a prerequisite for further clinical development. During my master’s degree I was able to gain additional knowledge in areas of pharmacy. I gathered practical knowledge regarding biopharmaceutical aspects, e.g. biorelevant dissolution testing and PBPK modelling during a project in the area of pharmaceutical technology. Especially the latter experience encouraged me to continue research in this scientific area with a close connection to its pharmaceutical industry.