{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:19:42Z","timestamp":1788304782894,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Zagreb Faculty of Pharmacy and Biochemistry, Croatia","award":["251-62-01-15-27"],"award-info":[{"award-number":["251-62-01-15-27"]}]},{"name":"R&amp;D, PLIVA Croatia Ltd., TEVA Group Member, Croatia","award":["251-62-01-15-27"],"award-info":[{"award-number":["251-62-01-15-27"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: This study investigates the stabilisation mechanisms of azelaic acid nanosuspensions (AZA-NS) prepared by wet media milling (WMM) using hydroxypropyl methylcellulose (HPMC) and chitosan as stabilisers. The aim was to elucidate the physical interactions relevant for stabilisation and to evaluate the effectiveness of a dual stabiliser approach to improve AZA-NS stability. Methods: AZA-NS were characterised using Fourier transform infrared spectroscopy (FTIR) to evaluate the chemical interactions, differential scanning calorimetry (DSC) for thermal properties, atomic force microscopy (AFM) to analyse the adsorption of the stabiliser on the AZA surface and X-ray diffraction (XRD) to evaluate the crystallinity. Contact angle and immersion studies were performed to evaluate wettability, and alternative stabilisers were tested for comparison. Results: Highly concentrated AZA-NS (up to 20% drug loading) were successfully produced with particle sizes between 326.8 and 541.2 nm, which are in the optimal range for follicular drug delivery. FTIR confirmed stabilisation by adsorption and not by chemical interaction. DSC revealed a melting point depression, indicating a partial disorder of the crystal lattice. AFM imaging showed different adsorption patterns for HPMC and chitosan, suggesting better surface coverage compared to alternative stabilisers. XRD confirmed the retention of the AZA crystalline form after milling. Contact angle and immersion studies showed improved wettability due to the synergistic effects of HPMC and chitosan. Alternative stabilisers showed suboptimal performance, highlighting the superior stabilising potential of the HPMC\u2013chitosan combination. Conclusions: This study provides important insights into the dual stabilisation mechanisms and highlights the importance of combining steric and electrostatic stabilisers for the formulation of stable nanosuspensions of medium soluble drugs such as AZA. These results support the development of optimised nanosuspensions with increased stability and improved pharmaceutical applicability.<\/jats:p>","DOI":"10.3390\/pharmaceutics17040439","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T05:10:07Z","timestamp":1743397807000},"page":"439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterisation and Stabilisation Mechanisms of Azelaic Acid Nanosuspensions: Insights from a Dual Stabiliser System"],"prefix":"10.3390","volume":"17","author":[{"given":"Sandra","family":"Mio\u010di\u0107","sequence":"first","affiliation":[{"name":"R&D, PLIVA Croatia Ltd., Teva Group Member, Prilaz Baruna Filipovi\u0107a 25, 10000 Zagreb, Croatia"},{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Tori\u0107","sequence":"additional","affiliation":[{"name":"R&D, PLIVA Croatia Ltd., Teva Group Member, Prilaz Baruna Filipovi\u0107a 25, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Jureti\u0107","sequence":"additional","affiliation":[{"name":"R&D, PLIVA Croatia Ltd., Teva Group Member, Prilaz Baruna Filipovi\u0107a 25, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0936-4276","authenticated-orcid":false,"given":"Jelena","family":"\u0110okovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-5058","authenticated-orcid":false,"given":"Danijela","family":"Randjelovi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Technology and Metallurgy, National Institute of the Republic of Serbia, University of Belgrade, Njego\u0161eva 12, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6236-9730","authenticated-orcid":false,"given":"Sne\u017eana","family":"Savi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Ferderber","sequence":"additional","affiliation":[{"name":"R&D, PLIVA Croatia Ltd., Teva Group Member, Prilaz Baruna Filipovi\u0107a 25, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biserka-Cetina","family":"\u010ci\u017emek","sequence":"additional","affiliation":[{"name":"R&D, PLIVA Croatia Ltd., Teva Group Member, Prilaz Baruna Filipovi\u0107a 25, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2338-9739","authenticated-orcid":false,"given":"Jelena","family":"Filipovi\u0107-Gr\u010di\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, A. 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