Chronotherapeutic Circadian-Based Pulsatile Drug Delivery of Etodolac for Morning Stiffness in Rheumatoid Arthritis
DOI:
https://doi.org/10.52783/jns.v14.1879Keywords:
Etodolac, Chronotherapeutic, Chronomodulated, Microparticle, Eudragit, Chitosan, pH Dependent.Abstract
This study focuses on the development of chronomodulated delivery systems for Etodolac, aimed at optimizing therapeutic outcomes in rheumatoid arthritis management. Core and coated microparticles were formulated using chitosan and Eudragit polymers, employing varying drug-to-polymer ratios and stirring speeds to achieve precise release profiles. Scanning electron microscopy confirmed the uniformity and integrity of the microparticles, with particle sizes ranging from 20.52 ± 0.79 µm to 105.45 ± 6.74 µm. Encapsulation efficiencies reached up to 98.34 ± 0.09% in coated formulations, demonstrating enhanced drug retention. Drug release studies revealed that coated microparticles followed controlled and sustained release patterns, aligning with zero-order and Higuchi kinetics, suitable for chronomodulated delivery. FTIR analysis confirmed chemical compatibility between Etodolac and excipients, ensuring formulation stability. The findings indicate that optimized formulation parameters, including drug-to-polymer ratios, stirring speeds, and polymer coatings, enabled effective delivery aligned with rheumatoid arthritis chronotherapy, targeting peak symptoms in early morning hours. This study highlights the potential of Etodolac microparticles for tailored drug delivery, improving patient compliance and therapeutic efficacy in managing rheumatoid arthritis.
Downloads
Metrics
References
AODAH, A. H. Y. 2009. Design and evaluation of Chronotherapeutic drug delivery Systems for the treatment of Nocturnal asthma. Master Degree, King Saud University.
BALFOUR, J. A. & BUCKLEY, M. M. 1991. Etodolac. A reappraisal of its pharmacology and therapeutic use in rheumatic diseases and pain states. Drugs, 42, 274-99.
BOGIN, R. M. & BALLARD, R. D. 1992. Treatment of nocturnal asthma with pulsed release albuterol. Chest, 102, 362-366.
COCHRANE, G. M. & CLARK, T. J. H. 1975. A survey of asthma mortality in patients between 35 and 65 years in the greater London hospitals in 1971. Thorax, 30, 300-315.
DHAWAN, S., SINGLA, A. K. & SINHA, V. R. 2004. Evaluation of Mucoadhesive Properties of Chitosan Microspheres Prepared by Different Methods. AAPS PharmSciTech, 5, 1-7.
DUBEY, R. R. & PARIKH, R. H. 2004. Two-Stage Optimization Process for Formulation of Chitosan Microspheres. AAPS PharmSciTech, 5, 1-9.
GAO, J.-G., ZHANG, Y., YU, Y.-F., HAN, Y.-C., ZHANG, B.-Z. & GAO, C.-H. 2011. Preparation of chitosan microspheres loading of 3,5-dihydroxy-4-<i>i</i>-propylstilbene and in vitro release. Journal of Polymer Research, 18, 1501-1508.
HUANG, J., FU, X., CHEN, X., LI, Z., HUANG, Y. & LIANG, C. 2021. Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis. Front Immunol, 12, 686155.
JEYANTHI, R., MEHTA, R. C., THANOO, B. C. & DELUCA, P. P. 1997. Effect of processing parameters on the properties of peptide-containing PLGA microspheres. J Microencapsul., 14, 163-174.
JOSE, S., PREMA, M. T., CHACKO, A. J., THOMAS, A. C. & SOUTO, E. B. 2011. Colon specific chitosan microspheres for chronotherapy of chronic stable angina. Colloids and Surfaces B: Biointerfaces, 83, 277-283.
KIKUCHI, A., KAWABUCHI, M., SUGIHARA, M., SAKURAI, Y. & OKANOA, T. 1999. Pulsed dextran release from calcium-alginate gel beads. Journal of Controlled Release 47, 21-29.
KIKUCHI, A. & OKANO, T. 2002. Pulsatile drug release control using hydrogels. Adv. Drug Deliv. Rev., 54, 53-77.
LIU, F., LIU, L., XUEMIN, L. & ZHANG, Q. 2007. Preparation of chitosan-hyaluronate double-walled microspheres by emulsification-coacervation method. J Mater Sci: Mater Med, 18, 2215-2224.
LORENZO-LAMOSA, M. L., REMUN˜A´N-LO´PEZ, C., VILA-JATO, J. L. & ALONSO, M. L. 1998. Design of microencapsulated chitosan microspheres for colonic drug delivery. Journal of Controlled Release, 52, 109-118.
MCINNES, I. B. & SCHETT, G. 2011. The pathogenesis of rheumatoid arthritis. N Engl J Med, 365, 2205-19.
NGIAN, G. S. 2010. Rheumatoid arthritis. Aust Fam Physician, 39, 626-8.
PACHUAU, L. & MAZUMDER, B. 2009. A study on the effects of different surfactants on thylcellulose microspheres. International Journal of PharmTech Research, 1, 966-971.
PATEL, G. C. & PATEL, M. M. 2009. A comparative in vitro evaluation of enteropolymers for pulsatile drug delivery system. Acta Pharmaceutica Sciencia, 51, 243- 250.
PENA, M. 1990. Etodolac: analgesic effects in musculoskeletal and postoperative pain. Rheumatol Int, 10 Suppl, 9-16.
RADU, A. F. & BUNGAU, S. G. 2021. Management of Rheumatoid Arthritis: An Overview. Cells, 10.
ROY, P. & SHAHIWALA, A. 2009. Statistical optimization of ranitidine HCl floating pulsatile delivery system for chronotherapy of nocturnal acid breakthrough. European Journal of Pharmaceutical Sciences, 37, 363-369.
ROY, S., PANPALIA, S. G., NANDY, B. C., RAI, V. K., TYAGI, L. K., DEY, S. & MEENA, K. C. 2009. Effect of Method of Preparation on Chiosan Microspheres of Mefenamic Acid. International Journal of Pharmaceutical Sciences and Drug Research, 1, 36-42.
SHIVAKUMAR, H. N., SURESH, S. & DESAI, B. G. 2010. Design and Evaluation of controlled Onset Extended Release Multiparticulate Systems for Chronotherpeutic Delivery of Ketoprofen. J Mater Sci: Mater Med, 21, 2691-2699.
SHUKLA, P. G., KALIDHASS, B., SHAH, A. & PALASHKAR, D. V. 2002. Preparation and characterization of microcapsules of water soluble pesticide monocrotophs using polyurethane as carrier material. J Microencapsul., 19, 293-304.
SMOLEN, J. S., ALETAHA, D. & MCINNES, I. B. 2016. Rheumatoid arthritis. Lancet, 388, 2023-2038.
SMOLENSKY, M. H., LEMMER, B. & REINBERG, A. E. 2007. Chronobiology and chronotherapy of allergic rhinitis and bronchial asthma. Adv. Drug Deliv. Rev., 59, 852-882.
SONI, M. L., NAMDEO, K. P., JAIN, S. K., GUPTA, M., DANGI, J. S., KUMAR, M. & DANGI, Y. S. 2011. pH-Enzyme Di-dependent Chronotherapeutic Drug Delivery System of Theophylline for Nocturnal Asthma. Chem.Pharm.Bull., 59, 191-195.
UMADEVI, S. K., THIRUGANESHA, R., SURESHA, S. & REDDYA, K. B. 2010. Formulation and Evaluation of Chitosan Microspheres of Aceclofenac for Colon-Targeted Drug Delivery. Biopharm. Drug Dispos., 31, 407-427.
WARWICK, M. T. 1988. Epidemiology of nocturnal asthma. Am. J. Med., 58, 6-8.
WASSERMAN, A. M. 2011. Diagnosis and management of rheumatoid arthritis. Am Fam Physician, 84, 1245-52.
WILDING, R., DAVIS, S. S., POZZI, F., FURLANI, P. & GAZZANIGA, A. 1994. Enteric coated timed release system for colonic targeting. Int. J. Pharm, 111, 99-102.
ZVAIFLER, N. 1989. A review of the antiarthritic efficacy and safety of etodolac. Clin Rheumatol, 8 Suppl 1, 43-53.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
