(T1130-02-10) A Novel Approach to Mechanical Characterization of Pharmaceutical Lyospheres

Purpose: Lyosphere has been broadly used to deliver chemical and biotherapeutic entities. However, the fragile nature of lyospheres can result in challenges in operation, and there is no comprehensive understanding of its strength to resist directional stress. This research aimed to develop an appropriate approach to comprehensively evaluate lyospheres' strength and better inform the formulation and process development.

Methods: An innovative method was developed to probe the shear strength of lyospheres employing a highly sensitive rheometer bundled with a bespoke 3D-printed holder. Combined with microscopy (SEM and optical microscopy), the structure-property relationship between lyophilized microstructure and compressive and shear strength was studied under various relative humidity (RH). Furthermore, the finite element method (FEM) modeling revealed the stress distribution when lyosphere undergoes the deformation.

Results: It is found that fracture energy could be considered as an appropriate descriptor for mechanical performance of lyospheres. At different RH, the strength of lyospheres was inversely proportional to the residual moisture content. Microstructure of lyospheres is found to be critical to explain the anisotropic mechanical properties. An aligned honeycomb-like structure was shown to directly correlate different fracturing-modes (buckling, collapsing and scissoring). The platform method has been sucessfully used to measure lot-to-lot variation and shear strain and shear force have been found to be critical to determine the difference between high and low yield loss samples during primary packaging.

Conclusion: Using the newly established R&D platform combined both experimental and modeling approaches, the methods and results should provide insight for controlling lyospherical strength through formulation and processing.

References: 1. K.B. Preston, T.W. Randolph. Adv. Drug Deliv. Rev., 171 (2021), pp. 50-61
2. W. Wang. Int. J. Pharm., 203 (2000), pp. 1-60
3. Y.-J. Lin and H. Nie. Powder Tech. 410 (2022) 117868
4. H.X. Zhu, N.J. Mills. Int. J. Solids Struct., 37 (2000), pp. 1931-1949

3D Printed Novel Lyosphere Holder
Shear force and compressive force on lot-to-lot variation. Lot with high yield loss during packaging has a wide shear strain and atypical low shear force to break.