Influence of Reconstitution Methods and Diluents on the Physicochemical Characteristics of Poly-L-Lactic Acid...

Macroscopic and microscopic aggregation patterns of reconstituted poly-L-lactic acid (PLLA) products may vary with product formulation, diluent, preparation protocol, and time. This descriptive in vitro pilot study compared two commercial formulations, StiCol Volume (150 mg PLLA reconstituted to 9 mL) and StiCol Soft (50 mg PLLA reconstituted to 6 mL), under 11 diluent conditions and 2 composite preparation protocols: roller mixing for 30 min and manual shaking for 3 min followed by 3 h of hydration. One preparation was evaluated for each formulation-diluent-protocol combination. Gross appearance was documented immediately and at 15, 30, 45, and 60 min and 24 h; microscopy was performed at ×40 and ×100 from 15 min onward. Two evaluators applied an ordinal visual aggregation scale, and the findings were analyzed descriptively. In the observed preparations, the StiCol Soft formulation generally showed lower aggregation grades than StiCol Volume; however, the products differed in nominal PLLA concentration, particle size, and excipient composition, so this pattern cannot be attributed to concentration alone. SWFI-based conditions tended to show fewer microscopic clusters than NSS-based conditions. The roller/30 min protocol also tended to show lower grades than the manual/3 h protocol, although mixing mode and hydration duration were inseparable. Macroscopic upper-layer accumulation was interpreted as vertical phase separation with creaming/flotation-like behavior rather than sedimentation. These exploratory findings generate hypotheses for replicated studies incorporating standardized sampling, redispersibility, particle size, rheological, and injectability testing; they do not establish an administration window or improved clinical safety.