Spray-dried nanocrystal-loaded polymer microparticles for long-term release local therapies: an opportunity for poorly soluble drugs

Abstract

Nano- and micro-technologies can salvage drugs with very low solubility that were doomed to pre-clinical and clinical failure. A unique design approach to develop drug nanocrystals (NCs) loaded in extended release polymeric microparticles (MPs) for local treatments is presented here through the case of a potential osteoarthritis (OA) drug candidate for intra-articular (IA) administration. Optimizing a low-shear wet milling process allowed the production of NCs that can be subsequently freeze-dried (FD) and redispersed in a hydrophobic polymer-organic solvent solution to form spray-dried MPs. Results demonstrated a successful development of a ready-to-upscale formulation containing PLGA MPs with high drug NC encapsulation rates that showed a continuous and controlled drug release profile over four months. The screenings and procedures described allowed for identifying and overcoming common difficulties and challenges raised along the drug reduction to nano-size and spray-drying process. Above all, the technical knowledge acquired is intended for formulation scientists aiming to improve the therapeutic perspectives of poorly soluble drugs.

Graphical Abstract

Keywords:

• Osteoarthritis
• microparticles
• nanocrystals
• spray-drying
• PLGA

Disclosure statement

No potential conflict of interest was reported by the authors. Gaby Thonus owns subscription rights of Galapagos. Sam Corveleyn and Joke Meeus are employee of Galapagos and own subscription rights in the company.

CRediT authorship contribution statement

Rodríguez-Nogales C.: Methodology, Investigation, Data curation, Formal analysis, Writing-original draft. Meeus J.: Methodology, Investigation, Resources, Validation, Writing – review and editing. Thonus G.: Methodology, Investigation, Validation, Writing – review and editing. Corveleyn S.: Resources, Validation, Supervision, Writing – review and editing. Allémann E.: Conceptualization, Resources, Validation, Writing – review and editing, Supervision. Jordan O.: Conceptualization, Supervision, Validation, Writing – review and editing. All authors have approved the submitted final version. All authors have read and agreed to the published version of the manuscript. All authors listed from Galapagos have substantially contributed to the design of the work and interpretation of the data.

Data availability statement

The data presented in this study are available on request from the corresponding author.

Additional information

Funding

This research work was sponsored by Galapagos NV.