Comprehensive Analysis of Novel Synergistic Antioxidant Formulations: Insights into Pharmacotechnical, Physical, Chemical, and Antioxidant Properties


(1) Background: Oxidative stress plays a pivotal role in the pathogenesis of various diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and diabetes, highlighting the pressing need for effective antioxidant interventions.

(2) Methods: In this study, we aimed to develop and characterise two novel antioxidant formulations, F3 and F4, as therapeutic interventions for oxidative stress-related conditions.

(3) Results: The physicochemical characterisation, preformulation analysis, formulation, preparation of filling powders for capsules, capsule content evaluation, and antioxidant activity assessment of the two novel antioxidant formulations were assessed. These formulations comprise a combination of well-established antioxidants like quercetin, biotin, coenzyme Q10, and resveratrol. Through comprehensive testing, the formulations’ antioxidant efficacy, stability, and potential synergistic interactions were evaluated.

(4) Conclusions: The findings underscore the promising potential of these formulations as therapeutic interventions for oxidative stress-related disorders and highlight the significance of antioxidant interventions in mitigating their progression.


Oxidative stress is caused by a series of environmental factors including pathogens, UV rays, the action of herbicides, and pollution. Dietary factors are also one of the main causes of oxidative stress. Many of the drugs contain toxins that can cause the occurrence of processes that are the basis of the triggering of oxidative stress [1–3]. These can, in some cases, inhibit the functionality of DNA or the production of enzymes, both crucial in the stages of glycolysis and oxidation [4,5]. Limiting these activities can cause the production of a large amount of free radicals [6,7]. Free radicals cannot simply be eliminated, they act on cell membranes, modifying DNA structures, which results in the deformation or death of the respective cells (the result is what we see in the mirror, premature aging and a state of poor health) [8,9]. Oxidative stress, resulting from an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defence system, has been implicated as a key contributor to the pathogenesis of these disorders. Notable conditions associated with or influenced by oxidative stress encompass neurodegenerative diseases, cardiovascular diseases, cancer, diabetes, chronic inflammatory diseases, and age-related disorders [10–22]. On the other hand, oxidative stress arises from an imbalance between free radical generation and the body’s antioxidant defence mechanisms. This imbalance can lead to cellular damage, impacting proteins, DNA, and cellular functions [23–29]. The interplay between neuroplasticity and oxidative stress is intricate. However, elevated or persistent oxidative stress can disrupt neuroplasticity. It can cause cellular damage, interfere with signaling pathways critical for adaptive changes, and potentially impair the brain’s ability to adapt and learn [30,31].

Genetic mutations denote alterations in the DNA sequence arising from diverse factors, encompassing environmental influences, intrinsic cellular processes, or hereditary predispositions. These mutations can affect gene and protein functionalities, leading to variations in cellular mechanisms and operations. Oxidative stress itself can induce DNA damage and mutations, potentially exacerbating cellular dysfunction and genetic variations [32–34]. Certain genetic conditions are linked to compromised antioxidant pathways or impaired DNA repair mechanisms, heightening susceptibility to oxidative damage. Conditions such as familial amyotrophic lateral sclerosis (ALS) or specific hereditary cancers exemplify associations between mutations affecting cellular defences against oxidative stress [35,36]. Furthermore, oxidative stress-induced DNA damage can prompt mutations in pivotal genes governing cellular regulation, contributing to the onset of diverse ailments, including cancer, neurodegenerative disorders, and age related conditions [37–43].

A balanced diet is the best treatment against oxidative stress, thanks to the antioxidants found in fresh fruits and vegetables, which have the ability to annihilate the unhealthy surplus of free radicals. The most important sources of antioxidants are found in nature, in complex forms, and never alone. The polyvitamin complexes provided by fruits and vegetables are very beneficial for the whole body [44,45]. Strategies aimed at mitigating oxidative stress through lifestyle modifications, antioxidant-rich dietary interventions, regular physical exercise, stress management, and targeted medical therapies focusing on antioxidant pathways hold promise in managing or aenuating the risk of these disorders. Further research into understanding the intricate role of oxidative stress in the pathogenesis of these conditions is crucial for devising tailored therapeutic approaches aimed at alleviating oxidative damage and preventing disease progression [46–49]. To reduce oxidative damage, it is very important to avoid sources of oxidants (cigarees, alcohol, foods with a poor nutritional index, stress, etc.) or toxic substances (contaminated foods, polluted environments) and to increase the consumption of food rich in antioxidants [50,51].

In this study, two antioxidant formulations, F1 and F2, comprising quercetin, biotin, coenzyme Q10, and resveratrol, in different proportions were subjected to extensive physicochemical characterisation nd preformulation analysis to elucidate their composition and stability. Capsule content evaluation was conducted to assess the uniformity of dosage and confirm the presence of active ingredients within each capsule. Antioxidant activity, a critical parameter for assessing the therapeutic potential of antioxidant formulations, was evaluated using appropriate assays to measure radical scavenging activity, lipid peroxidation inhibition, and total antioxidant capacity. The novelty of this study lies in the integration of the synergistic combination of quercetin, biotin, coenzyme Q10, and resveratrol. While each of these compounds has been individually studied for its antioxidant properties, the synergistic interactions between them within the formulations represent a novel approach to combating oxidative stress. By harnessing the complementary mechanisms of action of these compounds, the formulations offer the potential for enhanced antioxidant efficacy compared to single-agent interventions. Additionally, the comprehensive characterisation and evaluation of the formulations’ physicochemical properties, formulation processes, capsule content, and antioxidant activity contribute to the novelty of this research. Literature research has primarily focused on their individual effects, with limited exploration of their combined synergistic actions within formulations. By integrating these compounds in different combinations and proportions into two distinct antioxidant formulations, F3 and F4, this study advances the state of the art by exploring novel combinations of antioxidants tailored for the prophylaxis and treatment of oxidative stress-related conditions.

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Quercetin and resveratrol (Shanghai Zhongxin Yuxiang Chemical Co., Ltd., Shanghai, China), biotin (Zheijiang Shengda Bio-Pharm Co., Ltd., Taizhou, China), and coenzyme Q10 (Changsha Phyto Nutrition Inc., Changsha, China) were purchased from Fagron Hellas, Trikala, Greece. All compounds were used as received. Avicel PH 102 was provided by DuPont™ Nutrition and Health, Newark, DE, USA, EXPLOTAB® by JRS PHARMA GmbH & Co. KG, Rosenberg, Germany, and LIGAMED® MF-2-V by Peter Graven NV, Venlo, Limburg, The Netherlands. ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), DPPH (2,2-Diphenyl-1-picrylhydrazyl), and TPTZ (2,4,6-tri(2-pyridyl)-1,3,5-triazine) were provided by Sigma-Aldrich Chemie GmbH, Tauirchen,Germany.

Neacșu, S.M.; Mititelu, M.; Ozon, E.A.; Musuc, A.M.; Iuga, I.D.M.; Manolescu, B.N.; Petrescu, S.; Pandele Cusu, J.; Rusu, A.; Surdu, V.-A.; et al. Comprehensive Analysis of Novel Synergistic Antioxidant Formulations: Insights into Pharmacotechnical, Physical, Chemical, and Antioxidant Properties. Pharmaceuticals 202417, 690.

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