The synthesis of indomethacin prodrugs for the formation of nanosuspensions by emulsion templated freeze drying

Taylor, J, Sharp, A ORCID: 0000-0003-3396-7464, Rannard, SP ORCID: 0000-0002-6946-1097, Arrowsmith, S and McDonald, TO ORCID: 0000-0002-9273-9173 (2025) The synthesis of indomethacin prodrugs for the formation of nanosuspensions by emulsion templated freeze drying Rsc Advances, 15 (51). pp. 43830-43843. ISSN 2046-2069, 2046-2069

Access the full-text of this item by clicking on the Open Access link.

Abstract

Emulsion-templated freeze drying (ETFD) is a versatile technique for producing nanosuspensions of poorly water-soluble drugs, but predicting formulation success remains a significant challenge. In this study, we investigate how structural modification of the model drug indomethacin, through esterification with a series of alkyl and aromatic groups, influences nanosuspension formation via ETFD. A panel of seven indomethacin prodrugs was synthesised and screened across binary combinations of water-soluble stabilisers. The resulting formulations were assessed based on particle diameter, polydispersity index (PDI), and visual dispersion quality. Analysis of stabiliser combinations revealed specific systems that consistently supported nanoparticle formation across multiple prodrugs. Additionally, there was a positive relationship between increased hydrophobicity, represented by the calculated log P, and the formation of viable nanosuspensions. Moreover, the stability of these nanosuspensions was assessed, revealing that esters with higher log P values exhibited better dispersion stability. The findings provide valuable insights into the selection of active pharmaceutical ingredients for nanosuspension formulation and further the understanding of the influence of drug properties on nanosuspension stability and production. This research contributes to the development of effective nanosuspension strategies for a wide range of poorly water-soluble pharmaceutical compounds.

Item Type:	Article
Uncontrolled Keywords:	34 Chemical Sciences, Generic health relevance
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Inst. Life Courses & Medical Sciences (T&R staff) Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Women's & Children's Health Faculty of Science & Engineering Faculty of Science & Engineering > School of Physical Sciences Faculty of Science & Engineering > School of Physical Sciences > Chemistry
Depositing User:	Symplectic Admin
Date Deposited:	17 Nov 2025 08:40
Last Modified:	28 Feb 2026 01:05
DOI:	10.1039/d5ra06900a
Open Access URL:	https://doi.org/10.1039/D5RA06900A
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3195451
Disclaimer:	The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate.