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Objective <p>The challenges associated with poorly water-soluble drugs have been recognized for several decades. Poor aqueous solubility directly impairs the bioavailability of a drug, but this can be significantly improved using a nanosuspension (NS) formulation strategy. In general, there is high variability in stabilizers that function with different drugs, and it is often difficult to predict which stabilizer will yield a stable NS formulation.</p> Methods <p>In this study, poly(2-oxazine)- and poly(2-oxazoline)-based triblock copolymers (P1 and P2) were evaluated and benchmarked against commonly used stabilizers for the preparation of NS formulations, specifically hydroxypropyl methylcellulose and Pluronic F68. This study initiates the validation of P1 and P2 polymers for a new application, as these materials have not been previously studied as stabilizers in oral NS formulations. Indomethacin was selected as a poorly water-soluble model drug for NS preparation using a wet-ball milling technique. The stability of the resulting NSs was monitored over 28&#xa0;days and their dissolution profiles were assessed under non-sink conditions.</p> Results <p>P1 and P2 demonstrated better particle size reduction, and stability properties compared to the traditional stabilizers. In particular, P1 presented a marked improvement in the dissolution profiles of indomethacin, significantly outperforming the other NS formulations and reference samples. Molecular dynamics simulations further revealed distinct differences in the interactions of P1 and P2 with the indomethacin crystal surface, supporting the experimental findings.</p> Conclusions <p>Overall, our study highlights the potential of P1 as a promising stabilizer for nanosuspensions, providing mechanistic insights into polymer-drug compatibility, improved dissolution performance, and formulation stability.</p> Graphical Abstract <p></p>

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Formulation and Evaluation of Indomethacin Nanosuspensions Stabilized by Poly(2-oxazine) and Poly(2-oxazoline)-Based Polymers for Solubility Enhancement

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月15日

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  • Erika Espo,
  • Dipti Potdar,
  • Kiana Baas,
  • Larissa Keßler,
  • Mengshi Yang,
  • Kārlis Bērziņš,
  • Marianna Kemell,
  • Topias Kiiskinen,
  • Anni Heinonen,
  • Josef Kehrein,
  • Ben J. Boyd,
  • Anssi-Pekka Karttunen,
  • Leena Peltonen,
  • Robert Luxenhofer,
  • Alex Bunker,
  • Tapani Viitala

摘要

Objective

The challenges associated with poorly water-soluble drugs have been recognized for several decades. Poor aqueous solubility directly impairs the bioavailability of a drug, but this can be significantly improved using a nanosuspension (NS) formulation strategy. In general, there is high variability in stabilizers that function with different drugs, and it is often difficult to predict which stabilizer will yield a stable NS formulation.

Methods

In this study, poly(2-oxazine)- and poly(2-oxazoline)-based triblock copolymers (P1 and P2) were evaluated and benchmarked against commonly used stabilizers for the preparation of NS formulations, specifically hydroxypropyl methylcellulose and Pluronic F68. This study initiates the validation of P1 and P2 polymers for a new application, as these materials have not been previously studied as stabilizers in oral NS formulations. Indomethacin was selected as a poorly water-soluble model drug for NS preparation using a wet-ball milling technique. The stability of the resulting NSs was monitored over 28 days and their dissolution profiles were assessed under non-sink conditions.

Results

P1 and P2 demonstrated better particle size reduction, and stability properties compared to the traditional stabilizers. In particular, P1 presented a marked improvement in the dissolution profiles of indomethacin, significantly outperforming the other NS formulations and reference samples. Molecular dynamics simulations further revealed distinct differences in the interactions of P1 and P2 with the indomethacin crystal surface, supporting the experimental findings.

Conclusions

Overall, our study highlights the potential of P1 as a promising stabilizer for nanosuspensions, providing mechanistic insights into polymer-drug compatibility, improved dissolution performance, and formulation stability.

Graphical Abstract