İZOSORBİD DİNİTRATIN MODİFİYE SALIM YAPAN ÇOK BİRİMLİ BİLEŞİMİNİN TABLET ŞEKLİNDE BASILMASI VE DEĞERLENDİRİLMESİ

Yıl 2024, Cilt: 48 Sayı: 1, 138 - 149, 20.01.2024

Dmytro Olıınykov Andrii Kaplaushenko Olena Kryvoviaz Olena Tozıuk

https://doi.org/10.33483/jfpau.1075143

Öz

Amaç: Bu çalışma, küresel matris granüllerinin tabletler şeklinde basılmasıyla izosorbid dinitratın çok birimli dozaj formunu oluşturmayı, optimum teknoloji parametrelerini seçmeyi ve elde edilen tabletleri değerlendirmeyi amaçlamıştır.
Gereç ve Yöntem: Tablet çekirdekleri, çeşitli oranlarda ve çeşitli tabletleme kuvvetleri kullanılarak aktif matris granülleri ve yardımcı granüllerin karışımlarından hazırlandı. Elde edilen tablet bileşimlerinin çözünme hızı profilleri, referans ürün ile karşılaştırılarak değerlendirildi.
Sonuç ve Tartışma: Used technological approach makes it possible to regulate the dissolution profile of tablets by changing the ratio of active granules with different kinetics of the active substance release. Aktif sferoidler ve yardımcı granüllerin optimum oranı, optimum basınç parametresi ile belirlendi. Elde edilen çok birimli tabletler Cardicket Retard'ınkine benzer etkin madde salım profili göstermişti. Kullanılan teknolojik yaklaşım, etkin maddenin farklı kinetiklerle salımı ile aktif granüllerin oranı kullanılarak tabletlerin çözünme profilini düzenlemeyi mümkün kılmaktadır.

Anahtar Kelimeler

Aktif maddenin salım profili, izosorbid dinitrat, küresel matris granülleri, multidozlu tabletler

TABLETING AND EVALUATION OF MULTIPLE-UNIT COMPOSITION OF ISOSORBIDE DINITRATE WITH MODIFIED RELEASE

Öz

Objective: This study was aimed to create a multiple-unit dosage form of isosorbide dinitrate by pressing spherical matrix granules into tablets, selecting the optimal technology parameters and evaluating the obtained tablets.
Material and Method: The tablet cores were prepared from mixtures of active matrix granules and shock-absorbing auxiliary granules in various ratios using diverse tabletting forces. The dissolution profiles of the obtained tablet compositions were evaluated in comparison with the reference preparation.
Result and Discussion: An optimal ratio of spheroids with the active component with auxiliary granules along with optimal compression parameters were determined. The resulting as multiple-unit tablets exhibited a release profile similar to that of Cardicket Retard. Used technological approach makes it possible to regulate the dissolution profile of tablets by changing the ratio of active granules with different kinetics of the active substance release.

Anahtar Kelimeler

Active substance release profile, as multiple-unit tablets, isosorbide dinitrate, spherical matrix granules

Kaynakça

• 1. Soman, B., Vijayaraghavan, G. (2017). The role of organic nitrates in the optimal medical management of angina. E-Journal of Cardiology Practice, 15(2).
• 2. Lutaj, M.I. (2015). Nitrates in the treatment of cardiovascular diseases. Guidelines. Association of Cardiologists of Ukraine, p.31.
• 3. Nikonov, V., Kinoshenko, Y., Kursov, S. (2021). Nitrates in clinical practice. Emergency Medicine, 16(4), 7–22. [CrossRef]
• 4. Deepika, B., Sameen, S., Nazneen, N., Madhavi, A., Raju, K.N., Rao, K.N.V., Dutt, K.R. (2018). Matrix drug delivery system-a review. European Journal of Pharmacetical Medical Research, 5(2), 150-154. [CrossRef]
• 5. Tangde, S.R., Saboo, G.Y. (2021). Sustained release matrix type drug delivery systems; a review. International Journal of Creative Research Thoughts, 9(3), 3965-3980.
• 6. Goyal, S., Agarwal, G., Agarwal, S., Karar, P.K. (2017). Oral sustained release tablets: An overview with a special emphasis on matrix tablet. American Journal of Advanced Drug Delivery, 5(4). [CrossRef]
• 7. Baldi, A. (2015). Recent technological advancements in multiparticulate formulations: the smart drug delivery systems. Asian Journal of Pharmaceutics, 9(4), S13.
• 8. Shah, S.J., Shah, P.B., Patel, M.S., Patel, M.R. (2015). A review on extended release drug delivery system and multiparticulate system. World Journal of Pharmaceutical Research 4(8), 724-747.
• 9. Lavanya, K., Senthil, V., Rathi, V. (2011). Pelletization technology: A quick review. International Journal of Pharmaceutical Sciences and Research, 2(6), 1337. [CrossRef]
• 10. Chen, T., Li, J., Chen, T., Sun, C.C., Zheng, Y. (2017). Tablets of multi-unit pellet system for controlled drug delivery. Journal of Controlled Release, 262, 222-231. [CrossRef]
• 11. Gharge, V., Sharma, P.K., Gonjari, I.D., Bhandari, A. (2014). Multiple-unit controlled release platform formulation by wruster process. International Journal of Pharmacy and Pharmaceutical Sciences, 6(2), 107-113.
• 12. Al-Hashimi, N., Begg, N., Alany, R.G., Hassanin, H., Elshaer, A. (2018). Oral modified release multiple-unit particulate systems: compressed pellets, microparticles and nanoparticles. Pharmaceutics, 10(4), 176. [CrossRef]
• 13. Oliinykov, D.S., Kaplaushenko, A.H. (2019). Substantiation of manufacture technology development for the tablets of isosorbide dinitrate with modified release. Current Issues In Pharmacy And Medicine: Science And Practice, 12(2), 160-165. [CrossRef]
• 14. Muley, S.S., Nandgude, T., Poddar, S.K. (2016). Extrusion–spheronization a promising pelletization technique: In-depth review. Asian Journal of Pharmaceutical Sciences, 11, 684-699. [CrossRef]
• 15. Lopez, F., Ernest, T., Tuleu, C., Gul, M.O. (2015). Formulation approaches to pediatric oral drug delivery: Benefits and limitations of current platforms. Expert Opinion on Drug Delivery, 12, 1727-1740. [CrossRef]
• 16. Cerea, M., Pattarino, F., Foglio Bonda, A., Palugan, L., Segale, L., Vecchio, C. (2016). Preparation of multiparticulate systems for oral delivery of a micronized or nanosized poorly soluble drug. Drug Development and Industrial Pharmacy, 42, 1466-1475. [CrossRef]
• 17. Oliinykov, D., Kaplaushenko, A., Tregub, S., Kovalyova, K. (2020). Manufacture of spherical granules of isosorbide dinitrate with modified release. Journal of Faculty of Pharmacy of Ankara University, 44(3), 481-493. [CrossRef]
• 18. Agrawal, S., Fernandes, J., Shaikh, F., Patel, V. (2022). Quality aspects in the development of pelletized dosage forms. Heliyon, 8(2), E08956. [CrossRef]
• 19. Sarkar, S., Ang, B.H., Liew, C.V. (2014). Influence of starting material particle size on pellet surface roughness. AAPS PharmSciTech, 15, 131-139. [CrossRef]
• 20. Antal, I., Kállai, N., Luhn, O., Bernard, J., Nagy, Z.K., Szabó, B., Klebovich, I., Zelkó, R. (2013). Supramolecular elucidation of the quality attributes of microcrystalline cellulose and isomalt composite pellet cores. Journal Of Pharmaceutical And Biomedical Analysis, 84, 124-128. [CrossRef]
• 21. Elsergany, R.N., Lenhart, V., Kleinebudde, P. (2020). Influence of the surface tension of wet massing liquid on the functionality of microcrystalline cellulose as pelletization aid. European Journal of Pharmaceutics and Biopharmaceutics, 153, 285-296. [CrossRef]
• 22. Chadha, R., Bhandari, S. (2014). Drug-excipient compatibility screening-role of thermoanalytical and spectroscopic techniques. Journal of Pharmaceutical and Biomedical Analysis, 87, 82-97. [CrossRef]
• 23. Matsumoto, K., Kimura, S., Noguchi, S., Itai, S., Kondo, H., Iwao, Y. (2019). Mechanism of drug release from temperature-sensitive formulations composed of low-melting-point microcrystalline wax. Journal of Pharmaceutical Sciences, 108(6), 2086-2093. [CrossRef]
• 24. Krueger, C., Thommes, M., Kleinebudde, P. (2013). Spheronisation mechanism of MCC II-based pellets. Powder Technology, 238, 176-187. [CrossRef]
• 25. Ibrahim, M.A., Al-Anazi, F.K. (2013). Enhancement of the dissolution of albendazole from pellets using MTR technique. Saudi Pharmaceutical Journal, 21(2), 215-223. [CrossRef]
• 26. Zoubari, M.G. (2015) Water-insoluble polymers as binders for controlled release matrix and reservoir pellets. Dissertation zur Erlangung des akademischen Grades des Doktors der Naturwissenschaften.
• 27. Evonık Web site. Retrieved from https://healthcare.evonik.com/en/drugdelivery/oral-drug-delivery/oral-excipients/eudragit-portfolio. Accessed date 04.09.2021.
• 28. Oleynikov, D.S., Kaplaushenko, A.G. (2019). Development and validation of the HPLC-procedure for the quantitative determination of isosorbide dinitrate in matrix granules. Journal of Organic and Pharmaceutical Chemistry, 17(3), 51-58. [CrossRef]
• 29. European Pharmacopoeia Online. Retrieved from https://pheur.edqm.eu/. Accessed date 15.07.2021.
• 30. European Medicines Agency. Retrieved from https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-bioequivalence-rev1_en.pdf. Accessed date 02.11.2021.
• 31. Qureshi, S.A. (2016). A Critical Assessment of Current Practices of Drug Dissolution Testing Irrelevancies, their Causes and Suggestions to Address These. Journal of Applied Pharmacy, 8, 1-15.
• 32. European Medicines Agency. Retrieved from https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-q2r2-validation-analytical-procedures-step-2b_en.pdf. Accessed date 27.10.2022.
• 33. Tan, X., Hu, J. (2016). Investigation for the quality factors on the tablets containing medicated pellets. Saudi Pharmaceutical Journal: SPJ, 24, 507-514. [CrossRef]
• 34. MEGGLE Web site. Retrieved from https://www.meggle-pharma.com/en/lactose/14-starlac.html. Accessed date 19.07.2021.