Enhancing the Dissolution Performance of PVP-Based Boluses by Graphene Oxide Incorporation for Veterinary Applications

Abstract

Drug delivery systems for the food-processing animals in the veterinary field is particularly limited to the disease prevention and growth promotion. Therefore, optimizing dissolution performance of a targeted formulation may be achieved using a performance enhancer together with a commercial binder. In this study, poly(vinyl pyrrolidone) (PVP) was modified with graphene oxide (GO) to form a more stable binder matrix. The dissolution profiles of the formulations with and without the addition of GO into the bolus matrix were examined using two different methods: the continuous dissolution rig based on an artificial saliva and an in vitro dissolution test by the means of Daisy-II incubator. The kinetic models of First Order, Higuchi, Hixson-Crowell and Korsemeyer-Peppas were compared for a best fit of the experimental results obtained using the continuous dissolution rig and Daisy II. The results showed that PVP-containing tablets dissolved more rapidly, whereas PVP-GO combination provided a more controlled and prolonged release profile. Daisy II results in higher rate of dissolution for both formulations compared to the ones in the continuous dissolution rig.

Keywords

• Sustained-release
• Release kinetics
• Ruminants
• Graphene Oxide
• Artificial saliva

Veterinerlik Uygulamalarında PVP Bazlı Bolusların Grafen Oksit Eklenerek Salım Performansının Artırılması

Abstract

Veterinerlik alanında gıda kaynağı olarak yetiştirilen hayvanlar için ilaç salım sistemleri özellikle hastalık önleme ve büyümeyi teşvik etme ile sınırlıdır. Bu nedenle, hedeflenen bir formülasyonun salım performansının optimize edilmesi, ticari bir bağlayıcı ile birlikte bir performans arttırıcı kullanılarak gerçekleştirilebilir. Bu çalışmada, poli(vinil pirolidon) (PVP), daha kararlı bir bağlayıcı yapısı oluşturmak için formülasyon grafen oksit (GO) ile modifiye edilmiştir. Bolus yapısına GO eklenmiş ve eklenmemiş formülasyonların salım profilleri iki farklı yöntem kullanılarak incelenmiştir: yapay tükürük bazlı sürekli salım sistemi ve Daisy-II inkübatörü aracılığıyla bir in vitro çözünme testidir. Sürekli salım sistemi ve Daisy II kullanılarak elde edilen deneysel sonuçların en iyi uyumu için Birinci Derece, Higuchi, Hixson-Crowell ve Korsemeyer-Peppas'ın kinetik modelleri karşılaştırılmıştır. Sonuçlar, PVP içeren tabletlerin daha hızlı çözündüğünü, PVP-GO kombinasyonunun ise daha kontrollü ve uzun süreli bir salım profili sağladığını göstermiştir. Daisy II, sürekli salım sisteminde gerçekleştirilen formülasyonlara kıyasla, her iki formülasyon için de daha yüksek salım oranına neden olmuştur.

Keywords

• Kontrollü salım
• Salım kinetiği
• Ruminantlar
• Grafen oksit
• Yapay tükürük

References

1. [1] Cardinal, J. R. (1985). Controlled drug delivery: Veterinary applications. Journal of Controlled Release, 2(1), 393-403.
2. [2] Martinez, M. N., Lindquist, D., & Modric, S. (2010). Terminology challenges: Defining modified release dosage forms in veterinary medicine. Food and Drug Administration, Center for Veterinary Medicine, Office of New Animal Drug Evaluation. Rockville, MD.
3. [3] Ruan, X., Gao, X., Gao, Y., Peng, L., Ji, H., Guo, D., & Jiang, S. (2018). Preparation and in vitro release kinetics of ivermectin sustained-release bolus optimized by response surface methodology. PeerJ, 6, e5418. https://doi.org/10.7717/peerj.5418
4. [4] Kalász, H., & Antal, I. (2006). Drug excipients. Current Medicinal Chemistry, 13, 2535-2563.
5. [5] Khairnar, R. G., Darade, A. R., & Tasgaonkar, R. R. (2024). A review on tablet binders as a pharmaceutical excipient. World Journal of Biology, Pharmacy and Health Sciences, 17(3), 295–302.
6. [6] Amol, M., & Bhairav, B. A., & Saudager, R. B. (2017). Co-processed excipients for tabletting: Review article. Research Journal of Pharmacy and Technology, 10(7), 2427–2432.
7. [7] Shen, S. I., Jasti, B. R., & Li, X. (2003). Design of controlled-release drug delivery systems. In M. Kutz (Ed.), Standard handbook of biomedical engineering and design (Chap. 22, pp. 22.1-22). McGraw-Hill.
8. [8] Li, D., Muller, M. B., Gilje, S., Kaner, R. B., & Wallace, G. G. (2008). Processable aqueous dispersions of graphene nanosheets. Nature Nanotechnology, 3, 101–105.

9. [9] Yang, X., Wang, Y., Huang, X., Ma, Y., Huang, Y., Yang, R., et al. (2010). Multi-functionalized graphene oxide-based anticancer drug-carrier with dual-targeting function and pH-sensitivity. Journal of Materials Chemistry, 20, 3448–3454.
10. [10] Turgut, F. N. A., Konakcı, C. O., Arıkan, B., Comak, G., & Yıldıztuğay, E. (2024). Graphene oxide-based aerogel stimulates growth, mercury accumulation, photosynthesis-related gene expression, antioxidant efficiency and redox status in wheat under mercury exposure. Environmental Pollution, 342, 123117.
11. [11] Eshaghi, M. M., Pourmadadi, M., Rahdar, A., & Díez-Pascual, A. M. (2022). Novel carboxymethyl cellulose-based hydrogel with core–shell Fe₃O₄@SiO₂ nanoparticles for quercetin delivery. Materials, 15(24), 8711.
12. [12] Yaghoubi, F., Motlagh, N. S. H., Naghib, S. M., Haghiralsadat, F., Jaliani, H. Z., & Moradi, A. (2022). A functionalized graphene oxide with improved cytocompatibility for stimuli-responsive co-delivery of curcumin and doxorubicin in cancer treatment. Scientific Reports, 12(1), 1–18.
13. [13] Mostafavi, F. S., & Imani, R. (2021). Synthesis and characterization of gelatin-functionalized reduced graphene oxide for drug delivery application. Pathobiology Research, 23(5), 75–85.
14. [14] Pourmadadi, M., Yazdian, F., Hojjati, S., & Khosravi-Darani, K. (2021). Detection of microorganisms using graphene-based nanobiosensors. Food Technology and Biotechnology, 59(4), 496–506.
15. [15] Dinda, S. C., & Mukharjee, B. (2009). Gum cordia – A new tablet binder and emulsifier. Acta Pharmaceutica Sciencia, 51, 189–198.
16. [16] Wajid, A. S., Das, S., Irin, F., Ahmed, H. S. T., Shelburne, J. L., Parviz, D., Fullerton, R. J., Jankowski, A. F., Hedden, R. C., & Green, M. J. (2012). Polymer-stabilized graphene dispersions at high concentrations in organic solvents for composite production. Carbon, 50(2), 526–534.
17. [17] Zhang, J., Shen, G., Wang, W., Zhou, X., & Guo, S. (2010). Individual nanocomposite sheets of chemically reduced graphene oxide and poly(N-vinyl pyrrolidone): Preparation and humidity sensing characteristics. Journal of Materials Chemistry, 20, 10824–10828.
18. [18] Tiwari, H., Karki, N., Pal, M., Basak, S., Verma, R. K., Bal, R., Kandpal, N. D., Bisht, G., & Sahoo, N. G. (2019). Functionalized graphene oxide as a nanocarrier for dual drug delivery applications: The synergistic effect of quercetin and gefitinib against ovarian cancer cells. Colloids and Surfaces B: Biointerfaces, 178, 452–459.
19. [19] Soltis, M. P., Moorey, S. E., Egert-McLean, A. M., Voy, B. H., Shepherd, E. A., & Myer, P. R. (2023). Rumen biogeographical regions and microbiome variation. Microorganisms, 11(3), 747.
20. [20] Comtet-Marre, S., Parisot, N., Lepercq, P., Chaucheyras-Durand, F., Mosoni, P., Peyretaillade, E., & Forano, E. (2023). Lignocellulose degradation by rumen bacterial communities: New insights from metagenome analyses. Environmental Research, 226, 115785.
21. [21] McDougall, E. (1948). Studies on ruminant saliva: The composition and output of sheep’s saliva. Biochemical Journal, 43, 99–109.
22. [22] Tassone, S., Fortina, R., & Peiretti, P. G. (2020). In vitro techniques using the Daisy II incubator for the assessment of digestibility: A review. Animals, 10(5), 775. https://doi.org/10.3390/ani10050775
23. [23] Hummers, W. S., & Offeman, R. E. (1958). Preparation of graphitic oxide. Journal of the American Chemical Society, 80(6), 1339.
24. [24] Bilik, K., Çomak, G., & Sönmez, O. (2024). Graphene oxide-catalyzed microwave-assisted esterification of oleic acid to biodiesel. Biofuels, 953–960.
25. [25] Vadaga, A. K., Gudla, S. S., Nareboina, G. S. K., Gubbala, H., & Golla, B. (2024). Comprehensive review on modern techniques of granulation in pharmaceutical solid dosage forms. Intelligent Pharmacy, 2, 609–629.
26. [26] Comak, G., Durmuş, M., & Erez, İ. (2024). In vitro release kinetics and in vivo field trial performance of a long-term sustained-release bolus for Saanen goats. Turkish Journal of Engineering, 8(4), 712–719.
27. [27] McDougall, E.I. (1948). Studies on Ruminant Saliva. The Composition and Output of Sheep’s Saliva. Biochemical Journal, 43, 99–109.
28. [28] Marten, G. C., & Barnes, R. F. (1980). Prediction of energy digestibility of forages with in vitro rumen fermentation and fungal enzyme systems. In Standardization of Analytical Methodology for Feeds: Proceedings of a Workshop Held in Ottawa, Canada, 12–14 March 1979. International Development Research Centre.
29. [29] Yin, B., Wang, J., Jia, H., He, J., Zhang, X., & Xu, Z. (2016). Enhanced mechanical properties and thermal conductivity of styrene–butadiene rubber reinforced with polyvinylpyrrolidone-modified graphene oxide. Journal of Materials Science, 51, 5724–5737.
30. [30] Chang, X., Wang, Z., Quan, S., Xu, Y., Jiang, Z., & Shao, L. (2014). Exploring the synergetic effects of graphene oxide (GO) and polyvinylpyrrolidone (PVP) on poly(vinylidene fluoride) (PVDF) ultrafiltration membrane performance. Applied Surface Science, 316, 537–548.
31. [31] Huang, V., Ye, H., & Yam, K. L. (2013). Release mathematical model of active agent from packaging material into food. Mathematical Problems in Engineering, 10, 1–10.
32. [32] Paaeakh, M. P., Jose, P. A., Setty, C., & Christoper, G. V. P. (2018). Release kinetics–concepts and applications. International Journal of Pharmacy Research & Technology, 8, 1.
33. [33] Jahormi, L. P., Ghazali, M., Ashrafi, H., & Azadi, A. (2020). A comparison of models for the analysis of the kinetics of drug release from PLGA-based nanoparticles. Heliyon, 6(2), e03451.