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ORIGINAL RESEARCH article

Front. Chem.

Sec. Polymer Chemistry

This article is part of the Research TopicPolymer Functional CompositeView all 5 articles

Mechanistic Insights into Drying Methods: How They Govern the Structure and Bioactivity of Resveratrol-HP-β-CD Inclusion Complexes

Provisionally accepted
adilah  marwaadilah marwa1,2anton  bahtiaranton bahtiar1ariawan  gunadiariawan gunadi3Mahdi  JufriMahdi Jufri1*Witta  Kartika RestuWitta Kartika Restu4*
  • 1University of Indonesia, Depok, Indonesia
  • 2institut tarumanagara, Farmasi, Jakarta Selatan, Indonesia
  • 3Universitas Tarumanagara, West Jakarta, Indonesia
  • 4Badan Riset dan Inovasi Nasional Republik Indonesia, Central Jakarta, Indonesia

The final, formatted version of the article will be published soon.

apResveratrol (RES), a polyphenol with notable therapeutic potential, faces clinical limitations due to poor water solubility and low bioavailability. This study aimed to enhance the solubility and stability of RES by forming inclusion complexes with hydroxypropyl-β-cyclodextrin (HP-β-CD) using three drying methods: spray drying (SD), freeze-drying (FD), and solvent evaporation (SE). Phase solubility analysis confirmed the successful formation of a stable complex (K = 5278 M⁻¹) at an optimal 1:2 RES: HP-β-CD ratio. Among the dried products, the spray-dried complex (RHSD) demonstrated superior performance in moisture content, yield, and resveratrol content. It achieved the highest solubility enhancement (89-fold increase). In contrast, the freeze-dried complex (RHFD) showed the most potent antioxidant activity (IC₅₀ = 14.01 μg/mL). Physicochemical characterization via FTIR confirmed the formation of the inclusion complex. At the same time, XRD and SEM analyses revealed that RHSD possessed an amorphous structure, whereas RHFD and RHSE exhibited semi-crystalline characteristics. Subsequent drug-release studies demonstrated that RHSD followed non-Fickian release kinetics, unlike the diffusion-controlled release of RHFD and RHSE. These findings demonstrate that spray drying produces complexes with optimal physicochemical properties for solubility and dissolution, while freeze drying better preserves antioxidant activity, providing crucial insights for developing resveratrol-cyclodextrin formulations in pharmaceutical applications.plications.

Keywords: Freeze dryer, Hydroxypropyl-β-cyclodextrin, Inclusion complex, resveratrol, Solvent evaporation, Spray dryer

Received: 26 Aug 2025; Accepted: 20 Nov 2025.

Copyright: © 2025 marwa, bahtiar, gunadi, Jufri and Restu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mahdi Jufri, mahdijufri@farmasi.ui.ac.id
Witta Kartika Restu, witt001@brin.go.id

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