Controlled Release Gel Encompassing Curcumin Microspheres and Diclofenac Diethylamine for Feat Against Arthritis Inflammation

Author(s): Prabha Singh*, Shalan Dabre

Journal Name: Current Rheumatology Reviews

Volume 16 , Issue 2 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Diclofenac and curcumin is anticipated to have synergistic action. Hence, topical route of administration can be used in minimizing the issues with oral administration of both drugs.

Objective: This research aims at formulation of controlled release dosage form containing curcumin microspheres and diclofenac diethylamine and then incorporating it into gel formulation for treatment of inflammation associated with rheumatoid arthritis.

Methods: Curcumin microspheres were prepared, optimized and assayed. Gel containing microspheres was formulated and evaluated for physicochemical parameters like spreadability and viscosity. In vitro and ex vivo diffusion studies were carried out followed by evaluation of efficacy. Efficacy of the developed formulation was evaluated for anti-inflammatory activity.

Results: Particle size, Zeta potential, pH, spreadability and viscosity of optimized Batch F1 was found to be in range 0.5 µm - 5 µm,-27.9 mV, 6.2, 105 g cm/s and 7500 cps respectively. In vitro diffusion of developed gel of diclofenac diethylamine and curcumin was found to be 92.16 ± 0.0040 % in 3 h and 92.54 ± 0.0036 % in 12 h as compared to 79.57 ± 0.004 % diffusion in 2 h for marketed gel, thus showing controlled delivery of curcumin.

Conclusion: Decreased inflammation in formulation treated group by 72.53% and 50.75% in marketed treated group was seen. Thus the formulation developed showed prolonged activity as well as better anti-inflammatory activity.

Keywords: Curcumin microspheres, diclofenac diethylamine, o/w emulsion, inflammation, rheumatoid arthritis, formulation.

[1]
Spector WG, Willoughby DA. The inflammatory response. Bacteriol Rev 1963; 27: 117-54.
[http://dx.doi.org/10.1128/MMBR.27.2.117-154.1963] [PMID: 13989977]
[2]
El-Gamal MI, Bayomi SM, El-Ashry SM, Said SA, Abdel-Aziz AA, Abdel-Aziz NI. Synthesis and anti-inflammatory activity of novel (substituted)benzylidene acetone oxime ether derivatives: molecular modeling study. Eur J Med Chem 2010; 45(4): 1403-14.
[http://dx.doi.org/10.1016/j.ejmech.2009.12.041] [PMID: 20079558]
[3]
Franklin PX, Pillai AD, Rathod PD, et al. 2-Amino-5-thiazolyl motif: a novel scaffold for designing anti-inflammatory agents of diverse structures. Eur J Med Chem 2008; 43(1): 129-34.
[http://dx.doi.org/10.1016/j.ejmech.2007.02.008] [PMID: 17467123]
[4]
Paola RD, Cuzzocrea S. Predictivity and sensibility of animal models of arthritis. Autoimmun Rev 2007; 97: 43-8.
[5]
Cortright DN, Szallasi A. TRP channels and pain. Curr Pharm Des 2009; 15(15): 1736-49.
[http://dx.doi.org/10.2174/138161209788186308] [PMID: 19442187]
[6]
Cronan TA, Kaplan RM, Posner L, Blumberg E, Kozin F. Prevalence of the use of unconventional remedies for arthritis in a metropolitan community. Arthritis Rheum 1989; 32(12): 1604-7.
[http://dx.doi.org/10.1002/anr.1780321217] [PMID: 2597213]
[7]
Feldmann M, Brennan FM, Maini RN. Rheumatoid arthritis. Cell 1996; 85(3): 307-10.
[http://dx.doi.org/10.1016/S0092-8674(00)81109-5] [PMID: 8616886]
[8]
Gabriel SE, Crowson CS, Kremers HM, et al. Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years. Arthritis Rheum 2003; 48(1): 54-8.
[http://dx.doi.org/10.1002/art.10705] [PMID: 12528103]
[9]
Heyneman CA, Lawless-Liday C, Wall GC. Oral versus topical NSAIDs in rheumatic diseases: a comparison. Drugs 2000; 60(3): 555-74.
[http://dx.doi.org/10.2165/00003495-200060030-00004] [PMID: 11030467]
[10]
Shahrestani P, Mueller LD, Rose MR. Does aging stop? Curr Aging Sci 2009; 2(1): 3-11.
[http://dx.doi.org/10.2174/1874609810902010003] [PMID: 20021395]
[11]
Del Rosso JQ. Benzoyl Peroxide Microsphere Formulations: What is the Science Supporting Microsphere Vehicle Technology and Clinical Use? J Clin Aesthet Dermatol 2009; 2(9): 46-54.
[PMID: 20729960]
[12]
De Paz-Campos MA, Ortiz MI, Chávez Piña AE, Zazueta-Beltrán L, Castañeda-Hernández G. Synergistic effect of the interaction between curcumin and diclofenac on the formalin test in rats. Phytomedicine 2014; 21(12): 1543-8.
[http://dx.doi.org/10.1016/j.phymed.2014.06.015] [PMID: 25442263]
[13]
Lee JY, Shin TJ, Choi JM, et al. Antinociceptive curcuminoid, KMS4034, effects on inflammatory and neuropathic pain likely via modulating TRPV1 in mice. Br J Anaesth 2013; 111(4): 667-72.
[http://dx.doi.org/10.1093/bja/aet176] [PMID: 23719767]
[14]
Leamy AW, Shukla P, McAlexander MA, Carr MJ, Ghatta S. Curcumin ((E,E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) activates and desensitizes the nociceptor ion channel TRPA1. Neurosci Lett 2011; 503(3): 157-62.
[http://dx.doi.org/10.1016/j.neulet.2011.07.054] [PMID: 21855605]
[15]
De Paz-Campos MA, Chávez-Piña AE, Ortiz MI, Castañeda-Hernández G. Evidence for the participation of ATP-sensitive potassium channels in the antinociceptive effect of curcumin. Korean J Pain 2012; 25(4): 221-7.
[http://dx.doi.org/10.3344/kjp.2012.25.4.221] [PMID: 23091682]
[16]
Zhao X, Xu Y, Zhao Q, Chen CR, Liu AM, Huang ZL. Curcumin exerts antinociceptive effects in a mouse model of neuropathic pain: descending monoamine system and opioid receptors are differentially involved. Neuropharmacology 2012; 62(2): 843-54.
[http://dx.doi.org/10.1016/j.neuropharm.2011.08.050] [PMID: 21945716]
[17]
Ortiz MI, Granados-Soto V, Castañeda-Hernández G. The NO-cGMP-K+ channel pathway participates in the antinociceptive effect of diclofenac, but not of indomethacin. Pharmacol Biochem Behav 2003; 76(1): 187-95.
[http://dx.doi.org/10.1016/S0091-3057(03)00214-4] [PMID: 13679232]
[18]
Vellani V, Franchi S, Prandini M, et al. Effects of NSAIDs and paracetamol (acetaminophen) on protein kinase C epsilon translocation and on substance P synthesis and release in cultured sensory neurons. J Pain Res 2013; 6: 111-20.
[http://dx.doi.org/10.2147/JPR.S36916] [PMID: 23429763]
[19]
Jenita JL, Yathish M, Wilson B, Premakumari KB. Formulation and evaluation of microparticles containing curcumin for colorectal cancer. J Drug Deliv Ther 2012; 2(3): 125-8.
[http://dx.doi.org/10.22270/jddt.v2i3.127]
[20]
Ng SF, Rouse J, Sanderson D, Eccleston G. A comparative study of transmembrane diffusion and permeation of ibuprofen across synthetic membranes using franz diffusion cells. Pharmaceutics 2010; 2(2): 209-23.
[http://dx.doi.org/10.3390/pharmaceutics2020209] [PMID: 27721352]
[21]
Jain SK, Chourasia MK, Jain AK, Jain RK, Shrivastava AK. Development and characterization of mucoadhesive microspheres bearing salbutamol for nasal delivery. Drug Deliv 2004; 11(2): 113-22.
[http://dx.doi.org/10.1080/10717540490280750] [PMID: 15200010]
[22]
Mutimer MN, Riffkin C, Hill JA, Glickman ME, Cyr GN. Modern ointment base technology. II. Comparative evaluation of bases. J Am Pharm Assoc Am Pharm Assoc 1956; 45(4): 212-8.
[http://dx.doi.org/10.1002/jps.3030450406] [PMID: 13319092]
[23]
Bendele A. Animal models of rheumatoid arthritis. J Musculoskelet Neuronal Interact 2001; 1(4): 377-85.
[PMID: 15758488]
[24]
Gupta M, Mazumder U, Ramanathan SK, Thangavel SK. Studies on anti-inflammatory, analgesic and antipyretic properties of methanol extract of Caesalpinia bonducella leaves in experimental animal models. Iranian Journal of Pharmacology and Therapeutics 2003; 2(2): 30-4.
[25]
Posadas I, Bucci M, Roviezzo F, et al. Carrageenan-induced mouse paw oedema is biphasic, age-weight dependent and displays differential nitric oxide cyclooxygenase-2 expression. Br J Pharmacol 2004; 142(2): 331-8.
[http://dx.doi.org/10.1038/sj.bjp.0705650] [PMID: 15155540]
[26]
Chakraborty A, Devi RKB, Rita S, Sharatchandra Kh, Singh ThI. Preliminary studies on anti-inflammatory and analgesic activities of Spilanthes acmella in experimental animal models. Indian J Pharmacol 2004; 36(3): 148-50.
[27]
Badgujar VB, Jain PS, Patil RR, Haswani NG, Chaudhari SG. Anti-inflammatory activity of Helicteres isora L. stem bark extracts in rats. Asian Journal of Pharmaceutical and Clinical Research 2009; 2: 63-5.
[28]
Harmonised Tripartite Guideline ICH. Stability Testing of New Drug Substances and Products Q1A (R2 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use
[29]
Bajaj S, Singla D, Sakhuja N. Stability Testing of Pharmaceutical Products. J Appl Pharm Sci 2012; 02(03): 129-38.
[30]
Niyaz Basha B. Kalyani Prakasam, Divakar Goli. Formulation and evaluation of Gel containing Fluconazole-Antifungal Agent. Int J Drug Dev& Res 2011; 3(4): 109-28.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 2
Year: 2020
Page: [110 - 119]
Pages: 10
DOI: 10.2174/1573397115666191105142827
Price: $65

Article Metrics

PDF: 13
HTML: 1