PhD Scientific Days 2026

Pharmaceutical Sciences and Health Technologies 3.

Stability Enhancement of Alnus Diarylheptanoids by Cyclodextrin Complexation

Name of the presenter

Dohárszky, András

Institute/workplace of the presenter

Department of Pharmacognosy, Semmelweis University

Authors

Dr. András Dohárszky¹
1: Department of Pharmacognosy, Semmelweis University

Text of the abstract

Introduction
Diarylheptanoids derived from common alder (Alnus glutinosa L.) exhibit notable anticancer, anti-inflammatory, and antimicrobial activities, however, their practical application is limited by poor aqueous solubility and low stability. Cyclodextrin (CD) complexation represents a promising approach to overcome these limitations. CDs possess a polar outer surface that ensures good water solubility, while their hydrophobic inner cavity enables the encapsulation of apolar guest molecules via inclusion complex formation.

Aims
This study aimed to improve the pharmacokinetic properties and bioavailability of selected diarylheptanoids through CD complexation. The apparent complex stability constants (Kstab) of several diarylheptanoids were first determined by affinity capillary electrophoresis (ACE). Based on the ACE screening results, oregonin and hirsutenon, the most promising candidates were selected for UHPLC-monitored stability studies.

Methods
Kstab values were determined by ACE, an environmentally friendly, low sample-consuming technique, applying a broad set of native, neutral, positively, and negatively charged CD derivatives. Based on the screening results, stability was assessed using a validated UHPLC method. Samples were prepared in pH 7.4 phosphate buffer at various diarylheptanoid:CD molar ratios.

Results
The stabilizing effect strongly depended on both CD type and molar ratio. Negatively charged CD derivatives (subetadex, sugammadex) exhibited superior stabilizing capacity for both analytes during prolonged storage, outperforming both neutral and positively charged CDs.

Conclusion
CD charge and cavity size are critical determinants of stabilization efficiency. Negatively charged CD derivatives proved to be the most effective for long-term stabilization of both oregonin and hirsutenon, underscoring their potential as excipients in the development of diarylheptanoid-based formulations.

Funding
This work was funded by the SE 250+ Excellence PhD Scholarship.