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Interaction Studies Between Indomethacin Nanocrystals and PEO/PPO Copolymer Stabilizers

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Abstract

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.

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Acknowledgments

The authors acknowledge The Finnish Funding Agency for Innovation (TEKES, Finland; NanoForm project 40187/11) China Scholarship Council and The Academy of Finland for financial support. M.Sc. May Mah from University of Otago and M.Sc. Dongfei Liu from University of Helsinki are acknowledged for valuable discussion and suggestions, and Dr. Petri Ihalainen for providing the AFM image of the indomethacin layer precipitated on the SPR sensor slide.

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Authors and Affiliations

  1. Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland

    Peng Liu, Timo Laaksonen, Jouni Hirvonen & Leena Peltonen

  2. Division of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland

    Tapani Viitala, Alma Kartal-Hodzic & Huamin Liang

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  1. Peng Liu
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  2. Tapani Viitala
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Correspondence to Leena Peltonen.

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Liu, P., Viitala, T., Kartal-Hodzic, A. et al. Interaction Studies Between Indomethacin Nanocrystals and PEO/PPO Copolymer Stabilizers. Pharm Res 32, 628–639 (2015). https://doi.org/10.1007/s11095-014-1491-3

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  • DOI: https://doi.org/10.1007/s11095-014-1491-3

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