Characterization of Thermosensitive Gels for the Sustained Delivery of Dexketoprofen Trometamol for Dermal Applications

Abstract

In this report, the release properties of dexketoprofen (DEX) from propylene glycol (PG) and poloxamer gel systems were investigated. After formulation of gel systems composed of poloxamer 338 and PG, rheological experiment was conducted to investigate effects of PG on temperature-dependent viscoelasticity of poloxamer 338-based gels. It appeared that PG and poloxamer 338 could form gel systems with good thermosensitive properties, the gel system containing 2.5% and 5% PG showed similar thermosensitive properties. In vitro release studies were performed at two different temperatures, room temperature (25 ̊C ± 0.1 ̊C) and skin temperature (32 ̊C ± 0.1 ̊C), using Franz diffusion cells and showed decreased the release rate of DEX at skin temperature (32 ̊C) according the thermosensitive properties of poloxamer 338. Also released amount of DEX were decreased due to the use of high poloxamer concentration. At both temperatures, the highest release (39.35% at 32 °C and 31.78% at 25 ̊C in 8 hours) was obtained with 20%poloxamer + 5%PG, the lowest release (29.46% at 32 °C and 26.23% at 25 ̊C in 8 hours) was obtained with 25% poloxamer + 5% PG. After the drug releaseamount was examined, kinetic models (zero order, first order, Higuchi, Hixson-Crowell and Korsmeyer-Peppas) were investigated. In both temperatures (25 ̊C and 32 ̊C), the in vitro drug release profiles of poloxamer based formulations were fit to the Korsmeyer-Peppaskinetic model.

Keywords

• Poloxamer
• sustained release
• viscosity
• dexketoprofen trometamol
• propylene glycol

References

1. Abrantes, C. G., Duarte, D. & Reis, C. P. (2016). An Overview of Pharmaceutical Excipients: Safe or Not Safe? Journal of Pharmaceutical Sciences, 105(7), 2019–2026. Elsevier B.V. https://doi.org/10.1016/j.xphs.2016.03.019
2. Barkin, R. L. (2015). Topical Nonsteroidal Anti-Inflammatory Drugs: The Importance of Drug, Delivery, and Therapeutic Outcome. American Journal of Therapeutics, 22(5), 388–407. Lippincott Williams and Wilkins. https://doi.org/10.1097/MJT.0b013e3182459abd
3. Dewan, M., Bhowmick, B., Sarkar, G., Rana, D., Bain, M. K., Bhowmik, M. et al. (2015). Effect of methyl cellulose on gelation behavior and drug release from poloxamer based ophthalmic formulations. International Journal of Biological Macromolecules, 72, 706–710. Elsevier. https://doi.org/10.1016/j.ijbiomac.2014.09.021
4. Djekic, L., Čalija, B. & Medarević, Đ. (2020). Gelation behavior, drug solubilization capacity and release kinetics of poloxamer 407 aqueous solutions: The combined effect of copolymer, cosolvent and hydrophobic drug. Journal of Molecular Liquids, 303, 112639. Elsevier B.V. https://doi.org/10.1016/j.molliq.2020.112639
5. Dragicevic, N. & Maibach, H. I. (2015). Percutaneous penetration enhancers chemical methods in penetration enhancement: Modification of the stratum corneum. Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Modification of the Stratum Corneum. Springer-Verlag Berlin Heidelberg. https://doi.org/10.1007/978-3-662-47039-8
6. Dumortier, G., Grossiord, J. L., Agnely, F. & Chaumeil, J. C. (2006). A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharmaceutical Research, 23(12), 2709–2728. Springer Science and Business Media Deutschland GmbH. https://doi.org/10.1007/s11095-006-9104-4
7. Fakhari, A., Corcoran, M. & Schwarz, A. (2017). Thermogelling properties of purified poloxamer 407. Heliyon, 3(8), e00390. Elsevier Ltd. https://doi.org/10.1016/j.heliyon.2017.e00390
8. de Francisco, L. M. B., Rosseto, H. C., de Alcântara Sica de Toledo, L., dos Santos, R. S., de Souza Ferreira, S. B. & Bruschi, M. L. (2019). Organogel composed of poloxamer 188 and passion fruit oil: Sol-gel transition, rheology, and mechanical properties. Journal of Molecular Liquids, 289, 111170. Elsevier B.V. https://doi.org/10.1016/j.molliq.2019.111170

9. Gandra, S. C. R. (2013). The Preparation and Characterization of Poloxamer-Based Temperature-Sensitive Hydrogels for Topical Drug Delivery. ProQuest Dissertations and Theses, 112.
10. Ilbasmis-Tamer, S. (2017). Development and Validation of an Ultra Performance Liquid Chromatography Method for the Determination of Dexketoprofen Trometamol, Salicylic Acid and Diclofenac Sodium. Turkish Journal of Pharmaceutical Sciences, 14(1), 1–8. https://doi.org/10.4274/tjps.76588
11. Inal, O. & Yapar, E. A. (2013). Effect of mechanical properties on the release of meloxicam from poloxamer gel bases. Indian Journal of Pharmaceutical Sciences, 75(6), 700–706.
12. Jain, A. & Jain, S. K. (2016). In vitro release kinetics model fitting of liposomes: An insight. Chemistry and Physics of Lipids, 201, 1–66. https://doi.org/10.1016/j.chemphyslip.2016.10.005
13. Jalaal, M., Cottrell, G., Balmforth, N. & Stoeber, B. (2017). On the rheology of Pluronic F127 aqueous solutions. Journal of Rheology, 61(1), 139–146. https://doi.org/10.1122/1.4971992
14. Katakam, M., Ravis, W. R. & Banga, A. K. (1997). Controlled release of human growth hormone in rats following parenteral administration of poloxamer gels. Journal of Controlled Release, 49(1), 21–26. https://doi.org/10.1016/S0168-3659(97)01648-9
15. Korsmeyer, R. W., Gurny, R., Doelker, E., Buri, P. & Peppas, N. A. (1983). Mechanisms of solute release from porous hydrophilic polymers. International Journal of Pharmaceutics, 15(1), 25–35. https://doi.org/10.1016/0378-5173(83)90064-9
16. Leung, B., Dharmaratne, P., Yan, W., Chan, B. C. L., Lau, C. B. S., Fung, K. P. et al. (2020). Development of thermosensitive hydrogel containing methylene blue for topical antimicrobial photodynamic therapy. Journal of Photochemistry and Photobiology B: Biology, 203, 111776. https://doi.org/10.1016/j.jphotobiol.2020.111776
17. Lin, S. Y. & Kawashima, Y. (1985). The influence of three poly(oxyethylene)poly(oxypropylene) surface-active block copolymers on the solubility behavior of indomethacin. Pharmaceutica acta Helvetiae, 60(12), 339–44.
18. Mendonsa, N. S., Murthy, S. N., Hashemnejad, S. M., Kundu, S., Zhang, F. & Repka, M. A. (2018). Development of poloxamer gel formulations via hot-melt extrusion technology. International Journal of Pharmaceutics, 537(1–2), 122–131. Elsevier B.V. https://doi.org/10.1016/j.ijpharm.2017.12.008
19. Öztürk, A. A., Yenilmez, E. & Yazan, Y. (2019). Dexketoprofen trometamol-loaded eudragit® rl 100 nanoparticle formulation, characterization and release kinetics. Acta Pharmaceutica Sciencia, 57(1), 69–84. https://doi.org/10.23893/1307-2080.APS.05705
20. Özyazici, M., Gökçe, E. H. & Ertan, G. (2006). Release and diffusional modeling of metronidazole lipid matrices. European Journal of Pharmaceutics and Biopharmaceutics, 63(3), 331–339. https://doi.org/10.1016/j.ejpb.2006.02.005
21. Parhi, R. & Suresh, P. (2015). Alginate-poloxamer beads for controlled release of metoprolol succinate. Turkish Journal of Pharmaceutical Sciences, 12(1), 59–66.
22. Peppas, N. A. (1985). Analysis of Fickian and non-Fickian drug release from polymers. Pharmaceutica Acta Helvetiae, 60(4), 110–111.
23. Ricci, E. J., Bentley, M. V. L. B., Farah, M., Bretas, R. E. S. & Marchetti, J. M. (2002). Rheological characterization of Poloxamer 407 lidocaine hydrochloride gels. European Journal of Pharmaceutical Sciences, 17(3), 161–167. Elsevier. https://doi.org/10.1016/S0928-0987(02)00166-5
24. Ricci, E. J., Lunardi, L. O., Nanclares, D. M. A. & Marchetti, J. M. (2005). Sustained release of lidocaine from Poloxamer 407 gels. International Journal of Pharmaceutics, 288(2), 235–244. https://doi.org/10.1016/j.ijpharm.2004.09.028
25. Siepmann, J. & Peppas, N. A. (2001). Mathematical modeling of controlled drug delivery. Advanced Drug Delivery Reviews, 48(2–3), 137–138. https://doi.org/10.1016/S0169-409X(01)00111-9
26. Siepmann, J. & Siepmann, F. (2008). Mathematical modeling of drug delivery. International Journal of Pharmaceutics, 364(2), 328–343. https://doi.org/10.1016/j.ijpharm.2008.09.004
27. Soliman, K. A., Ullah, K., Shah, A., Jones, D. S. & Singh, T. R. R. (2019). Poloxamer-based in situ gelling thermoresponsive systems for ocular drug delivery applications. Drug Discovery Today, 24(8), 1575–1586. Elsevier Ltd. https://doi.org/10.1016/j.drudis.2019.05.036
28. Soni, G. & Yadav, K. S. (2014). High encapsulation efficiency of poloxamer-based injectable thermoresponsive hydrogels of etoposide. Pharmaceutical Development and Technology, 19(6), 651–661. https://doi.org/10.3109/10837450.2013.819014
29. Sorasitthiyanukarn, F. N., Rojsitthisak, Pornchai & Rojsitthisak, Pranee. (2017). Kinetic study of chitosan-alginate biopolymeric nanoparticles for the controlled release of curcumin diethyl disuccinate. Journal of Metals, Materials and Minerals, 27(2), 17–22. https://doi.org/10.14456/jmmm.2017.xx
30. Tirnaksiz, F. & Robinson, J. R. (2005). Rheological, mucoadhesive and release properties of Pluronic F-127 gel and Pluronic F-127/polycarbophil mixed gel systems. Pharmazie, 60(7), 518–523.
31. Trottet, L., Merly, C., Mirza, M., Hadgraft, J. & Davis, A. F. (2004). Effect of finite doses of propylene glycol on enhancement of in vitro percutaneous permeation of loperamide hydrochloride. International Journal of Pharmaceutics, 274(1–2), 213–219. https://doi.org/10.1016/j.ijpharm.2004.01.013
32. Wang, Y., Jiang, S., Wang, H. & Bie, H. (2017). A mucoadhesive, thermoreversible in situ nasal gel of geniposide for neurodegenerative diseases. PLoS ONE, 12(12). Public Library of Science. https://doi.org/10.1371/journal.pone.0189478
33. Zhang, Y., Huo, M., Zhou, J., Zou, A., Li, W., Yao, C. et al. (2010). DDSolver: An Add-In Program for Modeling and Comparison of Drug Dissolution Profiles. The AAPS Journal, 12(3), 263–271. https://doi.org/10.1208/s12248-010-9185-1