Zn2+ İyonları ile Çapraz Bağlı Sodyum Karboksimetil Selüloz Kürelerden Flurbiprofenin Kontrollü Salımı

Çalışmada, steroit olmayan anti-inflamatuar ilaç olan flurbiprofeni (FBP) kapsüllemek için sodyum karboksimetil selüloz (NaCMC) küreler Zn2+ iyonları ile çapraz bağlanarak elde edildi. Elde edilen küreler Fourier transform infrared (FTIR) spektroskopisi ve diferansiyel taramalı kalorimetri (DSC) ile karakterize edildi ve çapları optik mikroskop kullanılarak ölçüldü. Ayrıca, kürelerin denge şişme dereceleri, tutuklama değerleri, küre verim değerleri ve salım profilleri değerlendirildi. Küre verimi, tutuklama verimi ve FBP salımı üzerine NaCMC derişiminin, FBP yüklemesinin ve pH’nın etkisi incelendi. Flurbiprofenin kürelerden salımı pH 1.2 ortamında çok az iken, pH 7.4 bağırsak ortamında ise kontrollü bir şekilde gerçekleşti. NaCMC derişimi ve FBP yüklemesi arttıkça, kürelerden FBP salımı azaldı ve en yüksek ilaç salımı, NaCMC derişimi % 2 ve ilaç yüklemesi % 10 olan kürelerde gözlendi. Salım kinetikleri çoğunlukla Durum II olarak tanımlandı.

Anahtar Kelimeler:

Sodyum karboksimetil selüloz, Kontrollü ilaç salımı, Flurbiprofen, Küre

Controlled Release of Flurbiprofen from Sodium Carboxymethyl Cellulose Spheres Crosslinked with Zn2+ Ions

In the study, sodium carboxymethyl cellulose (NaCMC) spheres were obtained by crosslinking Zn2+ ions to encapsulate flurbiprofen (FBP), non-steroid anti-inflammatory drug. The spheres obtained were characterized by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) and their diameters were measured using an optical microscope. In addition, equilibrium swelling degrees, entrapment efficiencies, sphere yield values and release profiles of the spheres were evaluated. The effects of NaCMC concentration, FBP loading and pH on sphere yield, entrapment efficiency and FBP release were investigated. The release of flurbiprofen from the spheres was very low in pH 1.2 environment, whereas the release occurred in a controlled manner in the pH 7.4 intestinal environment. As the NaCMC concentration and FBP loading increased, FBP release from the spheres decreased and the highest drug release was observed in spheres with a NaCMC concentration of 2% and a drug loading of 10%. The release kinetics were mostly described as Case II.

Keywords:

Sodium carboxymethyl cellulose, Controlled drug release, Flurbiprofen, Sphere,

PDF

___

Akalın, G.O. and Pulat, M., 2018. Preparation and Characterization of Nanoporous Sodium Carboxymethyl Cellulose Hydrogel Beads. Hindawi Journal of Nanomaterials, 2018, 1-12.
Bulut, E., 2020 a. Flurbiprofen-Loaded Interpenetrating Polymer Network Beads Based on Alginate, Polyvinyl Alcohol and Methylcellulose: Design, Characterization and In Vitro Evaluation. Journal of Biomaterials Science-Polymer Edition, 31(13), 1671–1688.
Bulut, E., 2020 b. Chitosan Coated- and Uncoated-Microspheres of Sodium Carboxymethyl Cellulose/Polyvinyl Alcohol Crosslinked with Ferric Ion: Flurbiprofen Loading and In-vitro Drug Release Study. Journal of Macromolecular Science Part A-Pure and Applied Chemistry, 57(1), 72–82.
Bulut, E., 2021. Development and Optimization of Fe3+-Crosslinked Sodium Alginate-Methylcellulose Semi-interpenetrating Polymer Network Beads for Controlled Release of Ibuprofen. International Journal of Biological Macromolecules, 168, 823–833.
Bulut, E. and Şanlı, O., 2016. Novel Ionically Crosslinked Acrylamide-grafted Poly(vinyl alcohol)/Sodium Alginate/Sodium Carboxymethyl Cellulose pH-Sensitive Microspheres for Delivery of Alzheimer’s Drug Donepezil Hydrochloride: Preparation and Optimization of Release Conditions. Artificial Cells Nanomedicine and Biotechnology, 44(2), 431–442.
Cryer, B. and Feldman, M., 1998. Cyclooxygenase-1 and Cyclooxygenase-2 Selectivity of Widely Used Nonsteroidal Anti-Inflammatory Drugs. The American Journal of Medicine, 104(5), 413–421.
Elnashar, M.M., Yassin, M.A., Moneim, A.E.-F.A. and Bary, E.M.A., 2010. Surprising Performance of Alginate Beads for the Release of Low-Molecular-Weight Drugs. Journal of Applied Polymer Science, 116, 3021–3026.
Işıklan, N. and Erol, Ü.H., 2020. Design and Evaluation of Temperature-Responsive Chitosan/ Hydroxypropyl Cellulose Blend Nanospheres for Sustainable Flurbiprofen Release. International Journal of Biological Macromolecules, 159, 751–762.
Kim, M.S., Park, S.J., Gu, B.K. and Kim, C.-H., 2012. Ionically Crosslinked Alginate-Carboxymethyl Cellulose Beads for the Delivery of Protein Therapeutics. Applied Surface Science, 262, 28–33.
Kumbar, S.G., Soppimath, K.S. and Aminabhavi, T.M., 2003. Synthesis and Characterization of Polyacrylamide-Grafted Chitosan Hydrogel Microspheres for the Controlled Release of Indomethacin. Journal of Applied Polymer Science, 87, 1525–1536.
Li, J., Lu, J. and Li, Y., 2009. Carboxymethylcellulose/Bentonite Composite Gels: Water Sorption Behavior and Controlled Release of Herbicide. Journal of Applied Polymer Science, 112, 261–268.
Malipeddi, V.R., Dua, K. and Awasthi, R., 2016. Development and Characterization of Solid Dispersion-Microsphere Controlled Release System for Poorly Water-Soluble Drug. Drug Delivery and Translational Research, 6, 540–550.
Mallikarjuna, B., Madhusudana Rao, K, Sudhakar, P., Chowdoji Rao, K. and Subha, M.C.S., 2013. Chitosan Based Biodegradable Hydrogel Microspheres for Controlled Release of an Anti HIV Drug. Indian Journal of Advances in Chemical Science, 1(3), 144-151.
Peppas, N.A., 1985. Analysis of Fickian and Non-Fickian Drug Release from Polymer. Pharmaceutica Acta Helvetiae, 60, 110–111.
Pourjavadi, A., Barzegar, Sh. and Mahdavinia, G.R., 2006. MBA-Crosslinked Na-Alg/CMC as a Smart Full-Polysaccharide Superabsorbent Hydrogels. Carbohydrate Polymers, 66, 386–395.
Ramesh Babu, V., Rajinee Kanth, V., Mukund, J.M. and Aminabhavi, T.M., 2010. Novel Methyl Cellulose-Grafted-Acrylamide/Gelatin Microspheres for Controlled Release of Nifedipine. Journal of Applied Polymer Science, 115, 3542–3549.
Raut, N.S., Deshmukh, P.R., Umekar, M.J. and Kotagale, N.R., 2013. Zinc Cross-linked Hydroxamated Alginates for Pulsed Drug Release. International Journal of Pharmaceutical Investigation, 3(4), 194-202.
Ritger, P.L. and Peppas, N.A., 1987. A Simple Equation for Description of Solute Release II. Fickian and Anomalous Release from Swellable Devices. Journal of Controlled Release, 5, 37–42.
Taha, M.O., Nasser, W., Ardakani, A. and AlKhatib, H.S., 2008. Sodium Lauryl Sulfate Impedes Drug Release from Zinc-Crosslinked Alginate Beads: Switching from Enteric Coating Release into Biphasic Profiles. International Journal of Pharmaceutics, 350, 291–300.
Wang, Q., Wang, W., Wu, J. and Wang, A., 2012. Effect of Attapulgite Contents on Release Behaviors of a pH Sensitive Carboxymethyl Cellulose-g-poly(acrylic acid)/Attapulgite/Sodium Alginate Composite Hydrogel Bead Containing Diclofenac. Journal of Applied Polymer Science, 124, 4424–4432.