Biopharmaceutical Characterization and Stability of Nabumetone-Cyclodextrins Complexes Prepared by Grinding

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2025 Jan 8

PMID 39771473

Authors

David Klaric

Zeljka Soldin

Anna Vincze

Rita Szollath

Gyorgy Tibor Balogh

Mario Jug

Nives Galic

Affiliations

Soon will be listed here.

Abstract

Nabumetone (NAB) is a poorly soluble nonsteroidal anti-inflammatory prodrug (BCS class II drug) whose solubility is significantly improved by complexation with cyclodextrins (CDs). : The solid complexes, in a 1:1 molar ratio, were prepared by mechanochemical activation by grinding, using β-cyclodextrin (β-CD) and its derivatives, hydroxypropyl- and sulfobutylether-β-cyclodextrin (HP-β-CD and SBE-β-CD). The complexation was confirmed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and attenuated total reflectance Fourier-transformed infrared spectroscopy (ATR-FTIR). Obtained products were further characterized regarding their solubility, in vitro dissolution, permeability and chemical stability. : Co-grinding with HP-β-CD and SBE-β-CD yielded products that showed in vitro dissolution profiles in hydrochloric acid medium (pH 1.2) that were substantially different from that of pure NAB, yielding dissolution efficiency enhancements of 34.86 ± 1.64 and 58.30 ± 0.28 times, respectively, for the optimized products. Their in vitro dissolution and gastrointestinal permeability were also studied in a low-volume environment at pH 6.8, corresponding to the intestinal environment. Both β-CD derivatives increased NAB dissolution rate and NAB mass transport across the biomimetic membrane. The effect of β-CD derivatives on NAB chemical stability was studied under the stress conditions by the developed and validated UHPLC-DAD-HRMS method. In acidic conditions, pure and complexed NAB was prone to hydrolytic degradation, yielding one degradation product-pharmacologically inactive NAB metabolite. However, under the oxidative conditions at elevated temperatures, 10 NAB degradation products were identified from co-ground samples. All systems were stable during photo- and long-term stability studies. : NAB complexes with HP-β-CD and SBE-β-CD are promising candidates for pharmaceutical product development.

Citing Articles

Radiolytic Elimination of Nabumetone from Aqueous Solution: Degradation Efficiency, and Degradants' Toxicity.

Tartaro Bujak I, Klaric D, Lucic B, Bojanic K, Bujak M, Galic N Molecules. 2025; 30(1.

PMID: 39795121 PMC: 11722061. DOI: 10.3390/molecules30010064.

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