INVESTIGATING THE EFFECT OF pH AND ION STRENGTH ON LOADING AND RELEASE PROPERTIES OF DIFFERENT ION EXCHANGERS

Yıl 2023, Cilt: 47 Sayı: 2, 588 - 600, 20.05.2023

Özge İnal

https://doi.org/10.33483/jfpau.1264617

Öz

Objective: Ion-exchangers are inert, water-insoluble polymers with ionizable functional groups on their surface. They can be used for purposes such as disintegrating or taste masking in orally disintegrating dosage forms, or they can provide a pH-dependent controlled release.
Material and Method: The loading and release properties of different cation exchangers were investigated by loading Atenolol to Amberlite CG50, Dowex 50W-X2 and Smopex 101 as weak or strong resin and strong fiber, respectively. The effect of the ionic strength of the medium on the loading capacities of these materials were investigated in water and pH 7.4 HEPES buffer using batch method and loading was monitored by pH, zeta potential, FTIR and SEM analysis. Loading capacity was calculated UV spectrophotometrically. The effect of pH and ionic strength on the atenolol release was investigated by the dialysis bag method in pH 1.2 HCl, pH 6.8 PBS and pH 6.8 HEPES media.
Result and Discussion: Due to its low molecular weight and high pKa atenolol was successfully loaded with a capacity over 93%. As the pH could be balanced a higher loading capacity was achieved in HEPES buffer. The decrease in zeta potential values proved that the complexes were successfully obtained and the ionic complex formation was also monitored with FTIR and SEM micrographs. Atenolol did not get released in pH 1.2 medium, contrarily to pH 6.8 in which the functional groups are ionized. The higher amount of counter ions in PBS buffer also affected the release. The highest release rate was obtained with Amberlite. All ion-exchangers provided a pH-dependent release fitting to Higuchi or Zero order kinetics that shows diffusion. Boyd equation results also showed that diffusion mechanism was particle controlled.

Anahtar Kelimeler

Amberlite CG50, atenolol, cation-exchange materials, Dowex 50W, Smopex 101

pH VE İYON KUVVETİNİN İYON DEĞİŞTİRİCİLERİN YÜKLEME VE SALIM ÖZELLİKLERİ ÜZERİNE ETKİSİNİN İNCELENMESİ

Öz

Amaç: İyon değiştiriciler, yüzeylerinde iyonize olabilen fonksiyonel gruplar bulunan suda çözünmeyen inert polimerlerdir. Ağızda dağılan dozaj formlarında dağıtıcı veya tat maskeleyici gibi amaçlar için kullanılabilirler veya pH'ya bağlı kontrollü salım sağlayabilirler.
Gereç ve Yöntem: Atenolol kullanılarak üç farklı katyon değiştiricinin yükleme ve salım özellikleri araştırılmıştır. Kullanılan katyon değiştiriciler zayıf veya kuvvetli reçine ve kuvvetli fiber olarak sırasıyla Amberlite CG50, Dowex 50W-X2 ve Smopex 101 olarak seçilmiştir. Ortamın iyonik kuvvetinin bu malzemelerin yükleme kapasitelerine etkisi, beç yöntemi kullanılarak su ve pH 7.4 HEPES tamponunda araştırılmış ve yükleme pH, zeta potansiyeli, FTIR ve SEM analizi ile izlenmiştir. Yükleme kapasitesi UV spektrofotometrik yöntemle hesaplanmıştır. Ortam pH değeri ve iyonik kuvvetinin salım üzerindeki etkisi diyaliz torba kullanılarak pH 1.2 HCl, pH 6.8 PBS ve pH 6.8 HEPES ortamlarında incelenmiştir.
Sonuç ve Tartışma: Atenolol düşük molekül ağırlığı ve yüksek pKa değeri nedeniyle % 93'ün üzerinde bir kapasite ile başarıyla yüklenmiştir. pH dengelenebildiğinden, HEPES tamponunda daha yüksek bir yükleme kapasitesi elde edilmiştir. Zeta potansiyel değerlerindeki düşüş, iyon değiştirici-etken madde komplekslerinin başarılı bir şekilde elde edildiğini kanıtlamıştır. İyonik kompleks oluşumu FTIR ve SEM mikrografları ile de görüntülenmiştir. Atenolol, fonksiyonel grupların iyonize olduğu pH 6.8'in aksine pH 1.2 ortamında salınmamıştır. İçerdiği karşıt iyonlar nedeniyle PBS tamponunda daha yüksek miktarda salım sağlanmıştır. En hızlı salım Amberlite ile elde edilmiştir. Tüm iyon değiştiriciler, difüzyonu gösteren Higuchi veya Sıfır derece kinetikle pH'a bağlı bir salım göstermiştir. Boyd eşitlik sonucuna göre salım aynı zamanda partikülden kontrolle gerçekleşmiştir.

Anahtar Kelimeler

Amberlite CG50, atenolol, Dowex 50W, katyon değiştiriciler, Smopex 101

Kaynakça

• 1. Anand, V., Kandarap, R., Garg, S. (2001). Ion-exchange resins: carrying drug delivery forward, National Institute of Pharmaceutical Education and Research, 6(17), 905-914. [CrossRef]
• 2. Guo, X., Chang, R.K., Hussain, M. (2009). Ion-exchange resins as drug delivery carriers. Journal of Pharmaceutical Sciences, 98(11), 3886-3902. [CrossRef]
• 3. Ur-Rehman, F., Khan, S.N. (2012). Therapeutic applications of ion exchange resins. In: Ion Exchange Technology II: Applications, Inamuddin, D., Lugman M. (Eds). Springer Dordrecht. [CrossRef]
• 4. Singh, I., Rehni, A.K., Kalra, R., Joshi, G., Kumar, M., Aboul-Enein, H.Y. (2007). Ion exchange resins: Drug delivery and therapeutic applications, FABAD Journal of Pharmaceutical Sciences, 32, 91-100.
• 5. Patra, S., Samantaray, R., Pattnaik, S., Barik, B.B. (2010). Taste masking of etoricoxib by using ion-exchange resin. Pharmaceutical Development and Technology. 15(5), 511-517. [CrossRef]
• 6. Walsh, J., Cram, A., Woertz, K., Breitkreutz, J., Winzenburg, G., Turner, R., Tuleu, C. (2014). European formulation initiative. Playing hide and seek with poorly tasting paediatric medicines: Do not forget the excipients. Advanced Drug Delivery Reviews, 73, 14-33. [CrossRef]
• 7. Rajesh, A.M., Bhatt, S.A., Brahmbhatt, H., Anand, P.S., Popat, K.M. (2015). Taste masking of ciprofloxacin by ion-exchange resin and sustain release at gastric-intestinal through interpenetrating polymer network, Asian Journal of Pharmaceutical Sciences, 10(4), 331-340. [CrossRef]
• 8. Jeong, S.H., Park, K. (2008). Development of sustained release fast-disintegrating tablets using various polymer-coated ion-exchange resin complexes. International Journal of Pharmaceutics, 353, 195–204. [CrossRef]
• 9. Adelli, G.R., Balguri, S.P., Bhagav, P., Raman, V., Majumdar, S. (2017). Diclofenac sodium ion exchange resin complex loaded melt cast films for sustained release ocular delivery. Drug Delivery, 24(1), 370-379. [CrossRef]
• 10. Shang, R., Liu, C., Quan, P., Zhao, H., Fang, L. (2018). Effect of drug-ion exchange resin complex in betahistine hydrochloride orodispersible film on sustained release, taste masking and hygroscopicity reduction. International Journal of Pharmacetics, 545, 163-169. [CrossRef]
• 11. Xin, C., Li-hong, W., Yue, Y., Ya-nan, G., Qi-fang, W., Yang, Y., San-ming, L. (2012). A novel method to enhance the efficiency of drug transdermal iontophoresis delivery by using complexes of drug and ion-exchange fibers. International Journal of Pharmacetics, 428(1-2), 68-75. [CrossRef]
• 12. Gao, Y., Yuan, J., Liu, H., Yang, Y., Hou, Y., Li, S. (2014). Tramadol loading, release and iontophoretic characteristics of ion-exchange fiber. International Journal of Pharmaceutics, 465(1-2), 102-111. [CrossRef]
• 13. Nitanan, T., Akkaramongkolporn, P., Rojanarata, T., Ngawhirunpat, T., Opanasopit, P. (2013). Neomycin-loaded poly(styrene sulfonic acid-co-maleic acid) (PSSA-MA)/polyvinyl alcohol (PVA) ion exchange nanofibers for wound dressing materials. International Journal of Pharmaceutics, 448 (1), 71-78. [CrossRef]
• 14. Sun, X., Ma, C., Gong, W., Ma, Y., Ding, Y., Liu, L. 2020. Biological properties of sulfanilamide-loaded alginate hydrogel fibers based on ionic and chemical crosslinking for wound dressings, International Journal of Biological Macromolecules, 157, 522-529. [CrossRef]
• 15. Bajpai, S.K., Bajpai, M., Saxena, S. (2007). Chapter 3: Ion exchange resins in drug delivery, In: Sengupta AK. (Ed), Ion Exchange and Solvent Extraction. (pp. 103-145). CRC Press, Taylor and Francis Group. [CrossRef]
• 16. Hänninen, K., Kaukonen, A.M., Kankkunen, T., Hirvonen, J. (2003). Rate and extent of ion-exchange process: the effect of physico-chemical characteristics of salicylate anions. Journal of Controlled Release, 91(3), 449-463. [CrossRef]
• 17. Yuan, J., Gao, Y., Wang, X., Liu, H., Che, X., Xu, L., Yang, Y., Wang, Q., Wang, Y., Li, S. (2014). The load and release characteristics on a strong cationic ion-exchange fiber: kinetics, thermodynamics, and influences. Drug Design, Development and Therapy, 8, 945-955. [CrossRef]
• 18. Chen, Y.G., Sofińska-Chmiel, W., L., G.Y., Kołodyńska, D., Chen, S.H. (2021). Application of modern research methods for the physicochemical characterization of ion exchangers. Materials, 14, 7067. [CrossRef]
• 19. Malinovskaja, K., Laaksonen, T., Kontturi, K., Hirvonen, J. (2013). Ion-exchange and iontophoresis-controlled delivery of apomorphine. European Journal of Pharmaceutics and Biopharmaceutics, 83, 477-484. [CrossRef]
• 20. Hänninen, K., Kaukonen, A.M., Murtomäki, L., Hirvonen, J. (2007). Mechanistic evaluation of factors affecting compound loading into ion-exchange fibers, European Journal of Pharmaceutical Sciences, 31 (5), 306-317. [CrossRef]
• 21. Inal, O., Kiliçarslan, M., Ari, N., Baykara T. (2008). In vitro and in vivo transdermal studies of atenolol using iontophoresis. Acta Poloniae Pharmaceutica - Drug Research, 65(1),29-36.
• 22. Jeong, S.H., Park, K. (2008). Drug loading and release properties of ion-exchange resin complexes as a drug delivery matrix. International Journal of Pharmaceutics, 361, 26-32. [CrossRef]
• 23. Temmel, S., Kern, W., Luxbacher, T. (2006). Zeta potential of photochemically modified polymer surfaces. In: Grundke, K., Stamm, M., Adler, H.J. (Eds), Characterization of Polymer Surfaces and Thin Films. Progress in Colloid and Polymer Science, vol 132, (pp. 54-61). Springer, Berlin, Heidelberg. [CrossRef]
• 24. Gandi, G.K., Sikva, V.M.T.M., Rodrigues, A.E. (2007). Acetaldehyde dimethylacetal synthesis with Smopex 101 fibres as catalyst/adsorbent. Chemical Engineering Science, 62, 907-918. [CrossRef]
• 25. Doraswamy, K., Ramana, P.V. (2014). Controlled drug release studies of atenolol using differently sulfonated acryloxyacetophenone and methyl metacrylate copolymer resins as drug carriers. Chinese Journal of Polymer Science, 32(3), 280-291. [CrossRef]
• 26. Akkaramongkolporn, P., Wongsermsin, K., Opanasopit, P., Ngawhirunpat, T. (2010). Comparison between the effect of strongly and weakly cationic exchange resins on matrix physical properties and the controlled release of diphenhydramine hydrochloride from matrices. AAPS PharmSciTech, 11(3), 1104-1114. [CrossRef]
• 27. Leveneur, S., Murzin, D.Y., Salmi, T., Mikkola, J.P., Kumar, N., Eränen, K., Estel, L. (2009). Synthesis of peroxypropionic acid from propionic acid and hydrogen peroxide over heterogeneous catalysts. Chemical Engineering Journal, 147(2-3), 323-329. [CrossRef]
• 28. Paulo Costa, P., Sausa Lobo, J.M. (2001). Modeling and comparison of dissolution profiles. European Journal of Pharmaceutical Sciences, 13, 123-133. [CrossRef]