Journals / Afyon Kocatepe Üniversitesi Fen ve Mühendislik Bilimleri Dergisi / 2026 / Cilt: 25 Sayı: 5

Development and Characterization of TMZ Loaded HPMC-Montmorillonite Composites

TMZ Yüklü HPMC-Montmorillonit Kompozitlerinin Geliştirilmesi ve Karakterizasyonu

Hakan Çiftçi(AFYON KOCATEPE ÜNİVERSİTESİ)0000-0001-7910-7350
Firoozeh Panahianlarkey(AFYON KOCATEPE ÜNİVERSİTESİ)0009-0003-4445-1524
Pages
1164–1171
Publication Date
2025-10-01
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Nonetheless, the presence of regulated drug diffusion (Fickian mechanism) and ion exchange mechanism is linked to n coefficient values in the Korsmeyer-Peppas model being smaller than 0.5.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:In particular, the use of natural and large surface area natural inorganic materials such as clay minerals as carrier systems or adsorbents is important in terms of low cost.
📊
Key Findings & Data:As a result of the release tests, it was determined that the optimum formulation (F-6) showed best controlled release of TMZ from HPMC modified Mt.
💡
Conclusion & Impact:Nonetheless, the presence of regulated drug diffusion (Fickian mechanism) and ion exchange mechanism is linked to n coefficient values in the Korsmeyer-Peppas model being smaller than 0.5.
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:Montmorillonit · Bentonit · HPMC

Abstract

In particular, the use of natural and large surface area natural inorganic materials such as clay minerals as carrier systems or adsorbents is important in terms of low cost. This study investigated the utility of montmorillonite (Mt) clay in both its raw form and when modified with hydroxypropyl methylcellulose (HPMC) for the encapsulation and release of temozolomide (TMZ) active ingredient. For this purpose, the raw Mt clay was first purified using the sedimentation method. Then, six different formulations were prepared using Mt, HPMC, and TMZ in different composition ratios. The release of TMZ was evaluated under simulated stomach fluid conditions at varying time intervals. As a result of the release tests, it was determined that the optimum formulation (F-6) showed best controlled release of TMZ from HPMC modified Mt. The F-6 formulation exhibited a rapid TMZ release of 50% in the first 45 min. In the later period, it was determined that the oscillation occurred more slowly for 360 min and reached approximately 90%. Korsmeyer-Peppas and Hixson kinetics provided a clear explanation of the TMZ release of the generated formulations. Nonetheless, the presence of regulated drug diffusion (Fickian mechanism) and ion exchange mechanism is linked to n coefficient values in the Korsmeyer-Peppas model being smaller than 0.5.

Özet

Özellikle kil mineralleri gibi doğal ve yüksek yüzey alanlı doğal inorganik malzemelerin taşıyıcı sistem veya adsorban olarak kullanılması düşük maliyet açısından önemlidir. Bu çalışmada montmorillonit (Mt) kilinin hem ham haliyle hem de hidroksipropil metilselüloz (HPMC) ile modifiye edildiğinde temozolomit (TMZ) etken maddesinin kapsüllenmesi ve salınması için kullanılabilirliğini araştırıldı. Bu amaçla, ham Mt kili ilk önce sedimantasyon (çöktürme) yöntemi kullanılarak saflaştırıldı. Daha sonra, farklı bileşim oranlarında Mt, HPMC ve TMZ kullanılarak altı farklı formülasyon hazırlandı. TMZ'nin salımı, farklı zaman aralıklarında simüle edilmiş mide sıvısı koşulları altında değerlendirildi. Salım testleri sonucunda, optimum formülasyonun (F-6) HPMC ile modifiye edilmiş Mt'den en iyi kontrollü TMZ salımı gösterdiği belirlendi. F-6 formülasyonu ilk 45 dakikada %50'lik hızlı bir TMZ salımı sergiledi. Devam eden periyotta, TMZ salımının 360 dakika boyunca daha yavaş gerçekleştiği ve yaklaşık %90'a kadar ulaştığı belirlendi. Korsmeyer-Peppas ve Hixson kinetiği, üretilen formülasyonların TMZ salımını açık bir şekilde açıkladı. Bununla birlikte, düzenlenmiş ilaç difüzyonunun (Fickian mekanizması) ve iyon değişim mekanizmasının varlığı, Korsmeyer-Peppas modelindeki n katsayısı değerlerinin 0,5'ten küçük olmasıyla bağlantılıdır.

🔖

Cite This Article

Çiftçi, H., Panahianlarkey, F. (2025). Development and Characterization of TMZ Loaded HPMC-Montmorillonite Composites. Afyon Kocatepe Üniversitesi Fen ve Mühendislik Bilimleri Dergisi, Cilt: 25 Sayı: 5, 1164–1171. https://doi.org/10.35414/akufemubid.1625984

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (42)

  1. Arpa, M.D., Okur, N.Ü., Gök, M.K. and Cevher, E., 2024. Chitosan-based buccal mucoadhesive bilayer tablets enhance the bioavailability of tizanidine hydrochloride by bypassing the first-pass metabolism. Journal of Drug Delivery Science and Technology, 97, 105739. https://doi.org/10.1016/j.jddst.2024.105739
  2. Arpa, M.D., Kesmen, E. and Biltekin, S.N., 2023a. Novel sprayable thermosensitive benzydamine hydrogels for topical application: development, characterization, and in vitro biological activities. AAPS PharmSciTech, 24(8), 214. https://doi.org/10.1208/s12249-023-02674-w
  3. Arpa, M.D., Yağcılar, A.P. and Biltekin, S.N., 2023b. Novel benzydamine hydrochloride and chlorhexidine gluconate loaded bioadhesive films for local treatment of buccal infections. Journal of Drug Delivery Science and Technology, 84, 104497. https://doi.org/10.1016/j.jddst.2023.104497
  4. Boylu, F., Hojiyev, R., Ersever, G., Ulcay, Y. and Çelik, M.S., 2012. Production of ultrapure bentonite clays through centrifugation techniques. Separation Science and Technology, 47(6), 842-849. https://doi.org/10.1080/01496395.2011.634475
  5. Carretero, M.I. and Pozo, M., 2009. Clay and non-clay minerals in the pharmaceutical industry: Part I. Excipients and medical applications. Applied Clay Science, 46(1), 73-80. https://doi.org/10.1016/j.clay.2009.07.017
  6. Chakraborty, J., Roychowdhury, S., Sengupta, S. and Ghosh, S., 2013. Mg-Al layered double hydroxide–methotrexate nanohybrid drug delivery system: evaluation of efficacy. Materials Science and Engineering: C, 33(4), 2168-2174. https://doi.org/10.1016/j.msec.2013.01.047
  7. Çiftci, H., 2021. An introduction to montmorillonite purification. In Uddin, F., (Edt), Montmorillonite Clay. IntechOpen. https://doi.org/10.5772/intechopen.98188 Çiftçi, H., Ersoy, B. and Evcin, A., 2020a. Purification of Turkish bentonites and investigation of the contact angle, surface free energy and zeta potential profiles of organo-bentonites as a function of CTAB concentration. Clays and Clay Minerals, 68(3), 250-261. https://doi.org/10.1007/s42860-020-00070-0
  8. Çiftçi, H., Arpa, M.D., Gülaçar, İ.M., Özcan, L. and Ersoy, B., 2020b. Development and evaluation of mesoporous montmorillonite/magnetite nanocomposites loaded with 5-Fluorouracil. Microporous and Mesoporous Materials, 303, 110253. https://doi.org/10.1016/j.micromeso.2020.110253
  9. Çiftçi, H., 2022. Removal of methylene blue from water by ultrasound-assisted adsorption using low-cost bentonites. Chemical Physics Letters, 802, 139758. https://doi.org/10.1016/j.cplett.2022.139758
  10. Friuli, V., Pisani, S., Conti, B., Bruni, G. and Maggi, L., 2022. Tablet formulations of polymeric electrospun fibers for the controlled release of drugs with pH-dependent solubility. Polymers, 14(10), 2127. https://doi.org/10.3390/polym14102127
  11. Hassen, J.H., Abdalkadir, H.K. and Abed, S.F., 2023. An overview of medical applications of montmorillonite clay. Journal of Medical Science, 92(2), e826-e826. https://doi.org/10.20883/medical.e826
  12. Hojiyev, R., Ersever, G., Karaağaçlıoğlu, İ.E., Karakaş, F. and Boylu, F., 2016. Changes on montmorillonite characteristics through modification. Applied Clay Science, 127, 105-110. https://doi.org/10.1016/j.clay.2016.03.042
  13. Hojiyev, R., Ulcay, Y. and Çelik, M.S., 2017. Development of a clay-polymer compatibility approach for nanocomposite applications. Applied Clay Science, 146, 548-556. https://doi.org/10.1016/j.clay.2017.07.007
  14. Irani, M., Sadeghi, G.M. M. And Haririan, I., 2017. Gold coated poly (ε-caprolactonediol) based polyurethane nanofibers for controlled release of temozolomide. Biomedicine and Pharmacotherapy, 88, 667-676. https://doi.org/10.1016/j.biopha.2017.01.097.
  15. Iturrioz-Rodríguez, N., Sampron, N. And Matheu, A., 2023. Current advances in temozolomide encapsulation for the enhancement of glioblastoma treatment. Theranostics, 13(9), 2734. https://doi.org/10.7150/thno.82005
  16. Jatyan, R., Sahel, D.K., Singh, P., Sakhuja, R., Mittal, A. and Chitkara, D., 2023. Temozolomide-fatty acid conjugates for glioblastoma multiforme: In vitro and in vivo evaluation. Journal of Controlled Release, 359, 161-174. https://doi.org/0.1016/j.jconrel.2023.05.012
  17. Joshi, G.V., Kevadiya, B.D., Patel, H.A., Bajaj, H.C. and Jasra, R.V., 2009. Montmorillonite as a drug delivery system: intercalation and in vitro release of timolol maleate. International Journal of Pharmaceutics, 374(1-2), 53-57. https://doi.org/10.1016/j.ijpharm.2009.03.004
  18. Joshi, S.C., 2011. Sol–gel behavior of hydroxypropyl methylcellulose (HPMC) in ionic media including drug release. Materials, 4, 1861–1905. https://doi.org/10.3390/ma4101861
  19. Kevadiya, B.D., Patel, T.A., Jhala, D.D., Thumbar, R. P., Brahmbhatt, H., Pandya, M.P.,. and Bajaj, H.C., 2012. Layered inorganic nanocomposites: a promising carrier for 5-fluorouracil (5-FU). European Journal of Pharmaceutics and Biopharmaceutics, 81(1), 91-101. https://doi.org/10.1016/j.ejpb.2012.01.004
  20. Lagaly, G. and Dékány, I., 2013. Colloid clay science. In: Bergaya, F. and Lagaly, G., (Edts), Developments in Clay Science, Elsevier, Vol 5, pp. 243-345. https://doi.org/10.1016/B978-0-08-098258-8.00010-9
  21. Lee, Y.H., Kuo, T.F., Chen, B.Y., Feng, Y.K., Wen, Y.R., Lin, W.C. and Lin, F.H., 2005. Toxicity assessment of montmorillonite as a drug carrier for pharmaceutical applications: yeast and rats model. Biomedical Engineering: Applications, Basis and Communications, 17(02), 72-78. https://doi.org/10.4015/S1016237205000111
  22. Novak, S.D., Šporar, E., Baumgartner, S. and Vrečer, F., 2012. Characterization of physicochemical properties of hydroxypropyl methylcellulose (HPMC) type 2208 and their influence on prolonged drug release from matrix tablets. Journal of Pharmaceutical and Biomedical analysis, 66, 136-143. https://doi.org/10.1016/j.jpba.2012.03.032
  23. Orucoglu, E. and Haciyakupoglu, S., 2015. Bentonite modification with hexadecylpyridinium and aluminum polyoxy cations and its effectiveness in Se (IV) removal. Journal of Environmental Management, 160, 30-38. https://doi.org/10.1016/j.jenvman.2015.06.005
  24. Özkan, Z., Arpa, M.D., Özçatal, M. and Çiftçi, H., 2023. Preparation of Diatomite-Chitosan Composites for Loading and Release of Diphenhydramine HCl. Journal of Materials and Mechatronics: A, 4(2), 542-560. https://doi.org/10.55546/jmm.1326482 Pani, N.R. and Nath, L.K., 2014. Development of controlled release tablet by optimizing HPMC: Consideration of theoretical release and RSM. Carbohydrate Polymers, 104, 238-245. https://doi.org/10.1016/j.carbpol.2014.01.037
  25. Park, J.H., Shin, H.J., Kim, M.H., Kim, J.S., Kang, N., Lee, J.Y.,. and Kim, D.D., 2016. Application of montmorillonite in bentonite as a pharmaceutical excipient in drug delivery systems. Journal of Pharmaceutical Investigation, 46, 363-375. https://doi.org/10.1007/s40005-016-0258-8
  26. Salcedo, I., Aguzzi, C., Sandri, G., Bonferoni, M.C., Mori, M., Cerezo, P.,. and Caramella, C., 2012. In vitro biocompatibility and muco-adhesion of montmorillonite chitosan nanocomposite: A new drug delivery. Applied Clay Science, 55, 131-137. https://doi.org/10.1016/j.clay.2011.11.006
  27. Shah, L.A., da Silva Valenzuela, M.D.G., Ehsan, A.M., Díaz, F.R.V. and Khattak, N.S., 2013. Characterization of Pakistani purified bentonite suitable for possible pharmaceutical application. Applied Clay Science, 83, 50-55. https://doi.org/10.1016/j.clay.2013.08.007
  28. Sondi, I., Milat, O. and Pravdić, V., 1997. Electrokinetic potentials of clay surfaces modified by polymers. Journal of Colloid and Interface Science, 189(1), 66-73. https://doi.org/10.1006/jcis.1996.4753
  29. Stupp, R., Hegi, M.E., Mason, W.P., Van Den Bent, M.J., Taphoorn, M.J., Janzer, R.C.,. and Mirimanoff, R.O., 2009. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. The Lancet Oncology, 10(5), 459-466. https://doi.org/10.1016/S1470-2045(09)70025-7
  30. Tekin, N., Şafaklı, A., Budak, F. & Kara, A., 2019. Preparation, characterization, and antibacterial activity of organo-sepiolite/chitosan/silver bionanocomposites. Journal of Macromolecular Science, Part A, 56(5), 403-410. https://doi.org/10.1080/10601325.2019.1578620
  31. Viseras, C., Cerezo, P., Sanchez, R., Salcedo, I. and Aguzzi, C., 2010. Current challenges in clay minerals for drug delivery. Applied Clay Science, 48(3), 291-295. https://doi.org/10.1016/j.clay.2010.01.007
  32. Waghule, T., Swetha, K.L., Roy, A., Saha, R.N. and Singhvi, G., 2023. Exploring temozolomide encapsulated PEGylated liposomes and lyotropic liquid crystals for effective treatment of glioblastoma: in-vitro, cell line, and pharmacokinetic studies. European Journal of Pharmaceutics and Biopharmaceutics, 186, 18-29. https://doi.org/10.1016/j.ejpb.2023.03.004
  33. Wang, R., Peng, Y., Zhou, M. and Shou, D., 2016. Smart montmorillonite-polypyrrole scaffolds for electro-responsive drug release. Applied Clay Science, 134, 50-54. https://doi.org/10.1016/j.clay.2016.05.004
  34. Whittig, L.D.G., 1965. X-Ray Diffraction Techniques for Mineral Identification and Mineralogical Composition, Agronomy Monographs. https://doi.org/10.2134/agronmonogr9.1.c49
  35. Yang, J.H., Lee, J.H., Ryu, H.J., Elzatahry, A.A., Alothman, Z.A. and Choy, J.H., 2016. Drug–clay nanohybrids as sustained delivery systems. Applied Clay Science, 130, 20-32. https://doi.org/10.1016/j.clay.2016.01.021
  36. Yeşilyurt, Z., Boylu, F., Cinku, K., Esenli, F. and Çelik, M.S., 2014. Simultaneous purification and modification process for organobentonite production. Applied Clay Science, 95, 176-181. https://doi.org/10.1016/j.clay.2014.04.008
  37. Zhou, D., Law, D., Reynolds, J., Davis, L., Smith, C., Torres, J.L.,. & Zhou, C.C., 2014. Understanding and managing the impact of HPMC variability on drug release from controlled release formulations. Journal of Pharmaceutical Sciences, 103(6), 1664-1672. https://doi.org/10.1002/jps.23953
  38. Kevadiya, B.D., Patel, T.A., Jhala, D.D., Thumbar, R. P., Brahmbhatt, H., Pandya, M.P.,. and Bajaj, H.C., 2012. Layered inorganic nanocomposites: a promising carrier for 5-fluorouracil (5-FU). European Journal of Pharmaceutics and Biopharmaceutics, 81(1), 91-101. https://doi.org/10.1016/j.ejpb.2012.01.004
  39. Park, J.H., Shin, H.J., Kim, M.H., Kim, J.S., Kang, N., Lee, J.Y.,. and Kim, D.D., 2016. Application of montmorillonite in bentonite as a pharmaceutical excipient in drug delivery systems. Journal of Pharmaceutical Investigation, 46, 363-375. https://doi.org/10.1007/s40005-016-0258-8
  40. Salcedo, I., Aguzzi, C., Sandri, G., Bonferoni, M.C., Mori, M., Cerezo, P.,. and Caramella, C., 2012. In vitro biocompatibility and muco-adhesion of montmorillonite chitosan nanocomposite: A new drug delivery. Applied Clay Science, 55, 131-137. https://doi.org/10.1016/j.clay.2011.11.006
  41. Stupp, R., Hegi, M.E., Mason, W.P., Van Den Bent, M.J., Taphoorn, M.J., Janzer, R.C.,. and Mirimanoff, R.O., 2009. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. The Lancet Oncology, 10(5), 459-466. https://doi.org/10.1016/S1470-2045(09)70025-7
  42. Zhou, D., Law, D., Reynolds, J., Davis, L., Smith, C., Torres, J.L.,. & Zhou, C.C., 2014. Understanding and managing the impact of HPMC variability on drug release from controlled release formulations. Journal of Pharmaceutical Sciences, 103(6), 1664-1672. https://doi.org/10.1002/jps.23953