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Pharmaceutics
Volume 17
Issue 8
10.3390/pharmaceutics17081017
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Development and Preclinical Evaluation of Fixed-Dose Capsules Containing Nicergoline, Piracetam, and Hawthorn Extract for Sensorineural Hearing Loss

by
Lucia Maria Rus
1,
Andrei Uncu
2,
Sergiu Parii
2,
Alina Uifălean
1,
Simona Codruța Hegheș
1,
Cristina Adela Iuga
1,3,
Ioan Tomuță
4,
Ecaterina Mazur
2,5,
Diana Șepeli
6,
Irina Kacso
7,*,
Fliur Macaev
6,
Vladimir Valica
2,5 and
Livia Uncu
2,5
1
Department of Pharmaceutical Analysis, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania
2
Scientific Center of Medicines, “Nicolae Testemițanu” State University of Medicine and Pharmacy of Republic of Moldova, MD-2025 Chisinau, Moldova
3
Department of Personalized Medicine and Rare Diseases, MEDFUTURE—Institute for Biomedical Research, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania
4
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
5
Department of Pharmaceutical and Toxicological Chemistry, “Nicolae Testemițanu” State University of Medicine and Pharmacy of Republic of Moldova, MD-2025 Chisinau, Moldova
6
Institute of Chemistry, State University of Moldova, MD-2028 Chisinau, Moldova
7
National Institute for Research and Development of Isotopic and Molecular Technologies, 400293 Cluj-Napoca, Romania
*
Author to whom correspondence should be addressed.
Pharmaceutics 2025, 17(8), 1017; https://doi.org/10.3390/pharmaceutics17081017
Submission received: 5 July 2025 / Revised: 30 July 2025 / Accepted: 1 August 2025 / Published: 5 August 2025
(This article belongs to the Special Issue Natural Product Pharmaceuticals, 2nd Edition)
Versions Notes

Abstract

Background: Fixed-dose combinations have advanced in many therapeutic areas, including otorhinolaryngology, where hearing disorders are increasingly prevalent. Objectives: The present study focuses on developing and evaluating a new capsule combining nicergoline (NIC), piracetam (PIR), and hawthorn extract (HE) for the management of sensorineural hearing loss. Methods: The first phase methodology comprised preformulation studies (DSC, FTIR, and PXRD) to assess compatibility among active substances and excipients. Subsequently, four formulations were prepared and tested for flowability, dissolution behavior in acidic and neutral media, and stability under oxidative, thermal, and photolytic stress. Quantification of the active substances and flavonoids was performed using validated spectrophotometric and HPLC-UV methods. Results: Among the tested variants, the F1 formulation (4.5 mg NIC, 200 mg PIR, 50 mg HE, 2.5 mg magnesium stearate, 2.5 mg sodium starch glycolate, and 240.5 mg monohydrate lactose per capsule) displayed optimal technological properties, superior dissolution in acidic media, and was further selected for evaluation. The antioxidant activity of the formulation was confirmed through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, Trolox Equivalent Antioxidant Capacity (TEAC), and iron chelation tests, and was primarily attributed to the flavonoid content of the HE. Acute toxicity tests in mice and rats indicated a high safety margin (LD50 > 2500 mg/kg), while ototoxicity assessments showed no adverse effects on auditory function. Conclusions: The developed formulation displayed good stability, safety, and therapeutic potential, while the applied workflow could represent a model for the development of future fixed-dose combinations.
Keywords: fixed-dose combinations; nicergoline; piracetam; hawthorn extract; capsule formulation; preformulation; antioxidant assay fixed-dose combinations; nicergoline; piracetam; hawthorn extract; capsule formulation; preformulation; antioxidant assay

Share and Cite

MDPI and ACS Style

Rus, L.M.; Uncu, A.; Parii, S.; Uifălean, A.; Hegheș, S.C.; Iuga, C.A.; Tomuță, I.; Mazur, E.; Șepeli, D.; Kacso, I.; et al. Development and Preclinical Evaluation of Fixed-Dose Capsules Containing Nicergoline, Piracetam, and Hawthorn Extract for Sensorineural Hearing Loss. Pharmaceutics 2025, 17, 1017. https://doi.org/10.3390/pharmaceutics17081017

AMA Style

Rus LM, Uncu A, Parii S, Uifălean A, Hegheș SC, Iuga CA, Tomuță I, Mazur E, Șepeli D, Kacso I, et al. Development and Preclinical Evaluation of Fixed-Dose Capsules Containing Nicergoline, Piracetam, and Hawthorn Extract for Sensorineural Hearing Loss. Pharmaceutics. 2025; 17(8):1017. https://doi.org/10.3390/pharmaceutics17081017

Chicago/Turabian Style

Rus, Lucia Maria, Andrei Uncu, Sergiu Parii, Alina Uifălean, Simona Codruța Hegheș, Cristina Adela Iuga, Ioan Tomuță, Ecaterina Mazur, Diana Șepeli, Irina Kacso, and et al. 2025. "Development and Preclinical Evaluation of Fixed-Dose Capsules Containing Nicergoline, Piracetam, and Hawthorn Extract for Sensorineural Hearing Loss" Pharmaceutics 17, no. 8: 1017. https://doi.org/10.3390/pharmaceutics17081017

APA Style

Rus, L. M., Uncu, A., Parii, S., Uifălean, A., Hegheș, S. C., Iuga, C. A., Tomuță, I., Mazur, E., Șepeli, D., Kacso, I., Macaev, F., Valica, V., & Uncu, L. (2025). Development and Preclinical Evaluation of Fixed-Dose Capsules Containing Nicergoline, Piracetam, and Hawthorn Extract for Sensorineural Hearing Loss. Pharmaceutics, 17(8), 1017. https://doi.org/10.3390/pharmaceutics17081017

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