Aqueous Solubility and Degradation Kinetics of the Phytochemical Anticancer Thymoquinone; Probing the Effects of Solvents, pH and Light

Abstract

Thymoquinone (TQ) is a potent anticancer phytochemical with confirmed in vitro efficacy. Its clinical use has not yet established, and very few reports have documented its formulation. There also are no reports about the aqueous solubility and stability of this valuable drug, despite their direct correlation with the in vivo efficacy. In the current research, we have established and validated a stability-indicating HPLC method for the detection of TQ and its degradation products under different conditions. We then investigated the solubility and stability profiles of TQ in aqueous solutions. The stability study was aimed to determine the effect of pH, solvent type and light on the degradation process of TQ, along with the investigation of the kinetics of this degradation. The solubility of TQ varied in different aqueous solvents, and might be compromised due to stability issues. However, these findings confirm that the aqueous solubility is not the major obstacle for the drug formulations mainly due to the considerable water solubility (>500 μg/mL) that may be enough to exert pharmacologic effects if administered via parenteral route. Stability study results showed a very low stability profile of TQ in all the aqueous solutions with rapid degradation that varied with solvent type. The study of the degradation kinetics showed a significant effect of pH on the degradation process. The process followed first order kinetics at more acidic and alkaline pH values, and second order kinetics at pH 5-7.4, regardless of the solvent type. The results also expressed that OPEN ACCESSMolecules 2014, 19 5926 light has a greater impact on the stability of TQ as a shorter period of exposure led to severe degradation, independent of the solution pH and solvent type. Our results also addressed some discrepancies in previously published researches regarding the formulation and quantification of TQ with suggested solutions. Overall, the current study concludes that TQ is unstable in aqueous solutions, particularly at an alkaline pH, in addition to presenting severe light sensitivity. This data indicates the inappropriateness of aqueous solutions as pharmaceutical vehicles for TQ preparations. To the best of our knowledge, this is the first study describing TQ aqueous solubility and stability that may lead to the development of a stable and effective TQ formulation.

Non-Lamellar Liquid Crystalline Nanocarriers for Thymoquinone Encapsulation

“…The encapsulation efficiency (EE) of TQ was determined by using the following indirect method: the free (un-encapsulated) TQ was isolated from the nanodispersion by centrifugation (9600 rcf) for 10 min using a microcentrifuge (VWR TM 1207 Galaxy 7D ® Centrifuge, Radnor, PA, USA) and then its concentration was determined, as described in the previous report of Salmani et al [69], at a wavelength of 257 nm by using Cary 60 UV-VIS spectrophotometer (Agilent Technologies, Santa Clara, CA, USA). For TQ quantification, a calibration curve was prepared by dissolving the drug in ethanol at different concentrations in the range of 0.5-10 µg/mL.…”

Method Development and Validation using UV Spectrophotometry for Nigella sativa Oil Microparticles Quantification

“…Thymoquinone, thymol, thymohydroquinone, dithymoquinone and many others are among the active compounds isolated from the seed of N. sativa which responsible in providing the therapeutic properties (Zribi et al, 2014). Hydroquinone is described to give another peak around 290 nm but no distinguished peak is observed at 294 nm, although the same wavelength was used in other study to detect thymoquinone (Salmani et al, 2014). For thin layer chromatography, thymohydroquinone and thymoquinone give a typical fluorescence of the droplets under UV and blue light excitation which may be attributed to the presence of phenolic and other aromatic compounds (Botnick et al, 2012).…”

Ultrasonically Assisted Polysaccharide Microcontainers for Delivery of Lipophilic Antitumor Drugs: Preparation and in Vitro Evaluation

“…16,17 TQ is unstable in aqueous medium, particularly at an alkaline pH, and light sensitive. 18 Encapsulation could not only increases the TQ bioavailability, but also protect the drug from degradation caused by external factors, limiting its diffusion to normal tissues and preventing rapid release. 19 The aim of the current study was to fabricate ultrasonicallyinduced polysaccharide microcontainers loaded with thymoquinone and to study cellular uptake and cytotoxicity of the obtained MC in both 2D (monolayer culture) and 3D (tumor spheroids) conditions.…”