Interaction studies between indomethacin nanocrystals and PEO/PPO copolymer stabilizers

Peng Liu, Tapani Viitala, Alma Kartal-Hodzic, Huamin Liang, Timo Laaksonen, Jouni Hirvonen, Leena Peltonen*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

41 Citations (Scopus)


Purpose: The lack of effective screening methods and systemic understanding of interaction mechanisms complicates the stabilizer selection process for nanocrystallization. This study focuses on the efficiency of stabilizers with various molecular compositions and structures to stabilize drug nanocrystals. Methods: Five structurally different polymers were chosen as stabilizers for indomethacin nanocrystals. The affinity of polymers onto drug surfaces was measured using surface plasmon resonance (SPR) and contact angle techniques. Nanosuspensions were prepared using the wet-ball milling technique and their physico-chemical properties were thoroughly characterized. Results: SPR and contact angle measurements correlated very well with each other and showed that the binding efficiency decreased in the order L64 > 17R4 > F68 ≈ T908 ≈ T1107, which is attributed to the reduced PPO/PEO ratio and different polymer structures. The electrostatic interactions between the protonated amine of poloxamines and ionized indomethacin enhanced neither the affinity nor the properties of nanosuspensions, such as particle size and physical stability. Conclusions: A good stabilizer should have high binding efficiency, full coverage, and optimal hydrophobic/hydrophilic balance. A high affinity combined with short PEO chains (L64, 17R4) caused poor physical stability of nanosuspensions, whereas moderate binding efficiencies (F68, T908, T1107) with longer PEO chains produced physically stable nanosuspensions.

Original languageEnglish
Pages (from-to)628-639
Number of pages12
JournalPharmaceutical Research
Issue number2
Publication statusPublished - Feb 2015
Externally publishedYes
MoE publication typeA1 Journal article-refereed


  • Interaction studies
  • Nanocrystals
  • PEO/PPO copolymer
  • Surface plasmon resonance (SPR)
  • Wet-ball milling


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