A smart approach to enable preclinical studies in pharmaceutical industry: PLGA-based extended release formulation platform for subcutaneous applications

Abstract

Objective: Validation of a prospective new therapeutic concept in a proof of concept study is costly and time-consuming. In particular, pharmacologically active tool compounds often lack suitable pharmacokinetic (PK) properties for subsequent studies. The current work describes a PLGA-based formulation platform, encapsulating different preclinical research compounds into extended release microparticles, to optimize their PK properties after subcutaneous administration.

Significance: Developing a PLGA-based formulation platform offers the advantage of enabling early proof of concept studies in pharmaceutical research for a variety of preclinical compounds by providing a tailor-made PK profile.

Methods: Different model compounds were encapsulated into PLGA microparticles, utilizing emulsification solvent evaporation or spray drying techniques. Formulations aiming different release rates were manufactured and characterized. Optimized formulations were assessed in in vivo studies to determine their PK properties, with the mean residence time (MRT) as one key PK parameter.

Results: Utilizing both manufacturing methods, tested tool compounds were encapsulated successfully, with a drug load between 5% and 40% w/w, and an extended release time up to 250 h. In the following PK studies, the MRT was extended by a factor of 90, resulting in prolonged coverage of the required target through level. This approach was confirmed to be equally successful for additional internal compounds, verifying a general applicability of the platform.

Conclusion: For different active pharmaceutical ingredients (API), an optimized, tailor-made PK profile was obtained utilizing the described formulation platform. This approach is applicable for a variety of pharmacologically active tool compounds, reducing timelines and costs in preclinical research.

Keywords:

• PLGA
• extended release
• pharmacokinetic studies
• preclinical research
• formulation platform

Acknowledgements

The authors thank Bekir Karagül and Sylvia Suffrian for their expert technical support with spray drying, Nicole Gröner, Tanja Schwer and Diana Geiss for their technical support with formulation development, Nadine Klick, Heidi Assfalg, Anna Lachenmaier and Sigfried Wild for support with in vivo PK studies, Anastasia Zakharyuta for correction within the manuscript, Christian Kuttruff for providing der p 1 inhibitor and Peter Sieger and Bernhard Schmid for their export support within the project.

Disclosure statement

Patrick Strack, Tom Bretschneider, Raimund Külzer, Florian Sommer, and Achim Grube are employees of Boehringer Ingelheim Pharma GmbH & Co. KG. Olivia Merkel is employed by Ludwig Maximilian University of Munich.

Additional information

Funding

This work was fully funded by Boehringer Ingelheim Pharma GmbH & Co. KG.