Ternary cyclodextrin systems of terbinafine hydrochloride inclusion complexes: Solventless preparation, solid-state, and in vitro characterization

Balázs Attila Kondoros; Dávid Kókai; Katalin Burián; Milena Sorrenti; Laura Catenacci; Ildikó Csóka; Rita Ambrus

doi:10.1016/j.heliyon.2023.e21416

Ternary cyclodextrin systems of terbinafine hydrochloride inclusion complexes: Solventless preparation, solid-state, and in vitro characterization

Heliyon. 2023 Oct 21;9(11):e21416. doi: 10.1016/j.heliyon.2023.e21416. eCollection 2023 Nov.

Authors

Balázs Attila Kondoros¹, Dávid Kókai², Katalin Burián², Milena Sorrenti³, Laura Catenacci³, Ildikó Csóka¹, Rita Ambrus¹

Affiliations

¹ Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, H-6720, Szeged, Hungary.
² Albert Szent-Györgyi Health Center, Department of Medical Microbiology, Faculty of Medicine, University of Szeged, H-6725, Szeged, Hungary.
³ Department of Drug Sciences, University of Pavia, 27100, Pavia, Italy.

Abstract

Cyclodextrins (CD) are used extensively in the pharmaceutical industry to improve the water solubility and bioavailability of drugs. Preparing ternary systems by applying a third component can enhance these beneficial effects. The complexation methods of these ternary systems are the same as those of two-component complexes. These methods are solvent (co-evaporation, co-precipitation, etc.) or solventless "green" techniques (co-grinding, microwave irradiation, etc.). Using solvent-free methods is considered to be an economically and environmentally desirable technology. This study aimed to prepare ternary systems by the co-grinding method and evaluate the effect of a third component by comparing it to products obtained by solvent methods, binary systems, and marketed products. For that, we used terbinafine hydrochloride as a model drug, sulfobutyl-ether-beta-cyclodextrin as a complexation agent and 5 or 15 w/w% of polyvinylpyrrolidone K-90 (PVP) or hydroxypropyl methylcellulose (HPMC) as auxiliary components. Physicochemical evaluation (X-Ray Diffractometry, Differential Scanning Calorimetry, Thermogravimetry) showed that new solid phases were formed, while Scanning Electron Microscopy was performed to study morphological aspects of the products. Fourier transform infrared spectroscopic measurements suggested different intermolecular interactions depending on the type of polymer. In vitro dissolution studies showed beneficial effects of CD and further improvement with the applied polymers. Products showed less cell toxicity with one exception. Both polymers enhanced the physicochemical and in vitro properties, suggesting a greater bioavailability of the model drug. However, the percentage of polymers applied did not appear to be an influencing factor for these properties.

Keywords: Grinding; Hydroxypropyl methylcellulose; Mechanochemical activation; Polyvinyl pyrrolidone; Solvent-free green technology; Sulfobutyl-ether-beta-cyclodextrin.