Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

QbD-Enabled Systematic Development of Ileo-Colonic Targeted Novel Mucoadhesive Microspheres of Flurbiprofen

Author(s): Saikat Pande*, Janu Vashi and Ajay Solanki

Volume 19, Issue 3, 2022

Published on: 05 January, 2022

Page: [407 - 419] Pages: 13

DOI: 10.2174/1567201818666210708125036

Price: $65

Abstract

Background: Flurbiprofen (FLBP), used in the treatment of ulcerative colitis, has a short biological half-life. Frequent intake of FLBP may lead to some serious gastric complications, which makes FLBP an ideal candidate for sustained release preparation to the Ileo-colonic region of the gastrointestinal tract (GIT).

Objective: The objective of this study was to investigate the potential of Eudragit coated chitosan microspheres in delivering Flurbiprofen in a sustained manner to the Ileo-colonic region of the GIT for treatment of ulcerative colitis.

Methods: In the present study, mucoadhesive chitosan microspheres were prepared using the emulsion solvent evaporation method by varying different process parameters. Optimized chitosan microspheres were coated with Eudragit L-100 and Eudragit S-100. A 32 full factorial design was applied for optimization. The effect of independent variables (Eudragit L-100 to Eudragit S-100 ratio and stirring speed) on dependent variable i.e. percentage cumulative drug release (%CDR) at 3 h and 24 h was evaluated. The optimized batch was evaluated by FT-IR, DSC study, XRD study and SEM analysis.

Results: Discrete spherical shape chitosan microspheres with entrapment efficiency of up to 95.4% were obtained and selected for coating. Chitosan microspheres were coated successfully with different ratios of Eudragit L-100 to Eudragit S-100. The release profile of the optimized batch matches with the desired release profile. FLBP was found to be stable and molecularly dispersed in the polymer matrix.

Conclusion: Taken together it can be concluded that prepared microspheres may be considered as a suitable for delivering FLBP to the Ileo-colonic region of the GIT in the treatment of ulcerative colitis.

Keywords: Flurbiprofen, colon targeted delivery, chitosan, eudragit L-100, eudragit S-100, quality by design.

« Previous
Graphical Abstract
[1]
Chadha, S.; Kumar, A.; Srivastava, S.A.; Behl, T.; Ranjan, R. Inulin as a delivery vehicle for targeting colon-specific cancer. Curr. Drug Deliv., 2020, 17(8), 651-674.
[http://dx.doi.org/10.2174/1567201817666200527133719] [PMID: 32459607]
[2]
Deshmukh, R. Bridging the gap of drug delivery in colon cancer: The role of chitosan and pectin based nanocarriers system. Curr. Drug Deliv., 2020, 17(10), 911-924.
[http://dx.doi.org/10.2174/1567201817666200717090623] [PMID: 32679018]
[3]
Kim, H. Natural products to improve quality of life targeting for colon drug delivery. Curr. Drug Deliv., 2012, 9(2), 132-147.
[http://dx.doi.org/10.2174/156720112800234521] [PMID: 22283651]
[4]
Singh, R.J.; Dhaneshwar, S.S. Novel chewable colon targeted tablets of bumadizone calcium for treatment of ulcerative colitis: Formulation and optimization. J. Drug Deliv. Sci. Technol., 2016, 35, 172-183.
[http://dx.doi.org/10.1016/j.jddst.2016.06.001]
[5]
Singh, P.; Dhaneshwar, S.S. Investigating drug repositioning approach to design novel prodrugs for colon-specific release of fexofenadine for ulcerative colitis. Curr. Drug Deliv., 2017, 14(4), 543-554.
[http://dx.doi.org/10.2174/1567201813666161205160909] [PMID: 27919212]
[6]
Srivastava, A.; Gowda, D.V.; Madhunapantula, S.V.; Siddaramaiah, . Siddaramaiah. Development and efficacy assessment of an enteric coated porous tablet loaded with F4 fimbriae for oral vaccination of piglets against F4+ Escherichia coli infections. Curr. Drug Deliv., 2016, 13(1), 121-130.
[http://dx.doi.org/10.2174/1567201812999150727131119] [PMID: 26212139]
[7]
Cheng, G.; An, F.; Zou, M.J.; Sun, J.; Hao, X.H.; He, Y.X. Time- and pH-dependent colon-specific drug delivery for orally administered diclofenac sodium and 5-aminosalicylic acid. World J. Gastroenterol., 2004, 10(12), 1769-1774.
[http://dx.doi.org/10.3748/wjg.v10.i12.1769] [PMID: 15188503]
[8]
Bie, P.; Chen, L.; Li, X.; Li, L. Characterization of concanavalin A-conjugated resistant starch acetate bioadhesive film for oral colon-targeting microcapsule delivery system. Ind. Crops Prod., 2016, 84, 320-329.
[http://dx.doi.org/10.1016/j.indcrop.2016.02.023]
[9]
Maharshi, P.; Singh, S.K.; Gulati, M.; Yadav, A.K.; Garg, V.; Kumar, B.; Gowthamarajan, K. A novel three-pronged approach for colon delivery of sulfasalazine: concomitant use of pH- responsive, microbially triggered polymers and liquisolid technology. Curr. Drug Deliv., 2018, 15(7), 1038-1054.
[http://dx.doi.org/10.2174/1567201815666180320095703] [PMID: 29557742]
[10]
Amidon, S.; Brown, J.E.; Dave, V.S. Colon-targeted oral drug delivery systems: Design trends and approaches. AAPS PharmSciTech, 2015, 16(4), 731-741.
[http://dx.doi.org/10.1208/s12249-015-0350-9] [PMID: 26070545]
[11]
Kumar, D.; Saroha, K.; Goyal, G.; Yadav, D.; Sorout, A.; Verma, S. Microspheres for colon targeted drug delivery: A comprehensive review. Int. J. Pharma Sci., 2016, 1(4), 39-45.
[12]
Chandran, S.; Sanjay, K.S.; Ali Asghar, L.F. Microspheres with pH modulated release: Design and characterization of formulation variables for colonic delivery. J. Microencapsul., 2009, 26(5), 420-431.
[http://dx.doi.org/10.1080/02652040802424021] [PMID: 18821120]
[13]
Prajapati, B.; Jena, P.K.; Mehta, T.; Seshadri, S. Preparation and optimization of moxifloxacin microspheres for colon targeted delivery using Quality by Design approach: in vitro and in vivo study. Curr. Drug Deliv., 2016, 13(7), 1021-1033.
[http://dx.doi.org/10.2174/1567201813666160512145625] [PMID: 27174176]
[14]
Kean, W.F.; Antal, E.J.; Grace, E.M.; Cauvier, H.; Rischke, J.; Buchanan, W.W. The pharmacokinetics of flurbiprofen in younger and elderly patients with rheumatoid arthritis. J. Clin. Pharmacol., 1992, 32(1), 41-48.
[http://dx.doi.org/10.1002/j.1552-4604.1992.tb03786.x] [PMID: 1740536]
[15]
Davies, N.M. Clinical pharmacokinetics of flurbiprofen and its enantiomers. Clin. Pharmacokinet., 1995, 28(2), 100-114.
[http://dx.doi.org/10.2165/00003088-199528020-00002] [PMID: 7736686]
[16]
Patil, S.B.; Sawant, K.K. Chitosan microspheres as a delivery system for nasal insufflation. Colloids Surf. B Biointerfaces, 2011, 84(2), 384-389.
[http://dx.doi.org/10.1016/j.colsurfb.2011.01.030] [PMID: 21320767]
[17]
Gawde, P.; Agrawal, S. Design and characterization of eudragit coated chitosan microspheres of deflazacort for colon targeting. J. Pharm. Sci., 2012, 5(9), 4867-4870.
[18]
El-Say, K.M. Maximizing the encapsulation efficiency and the bioavailability of controlled-release cetirizine microspheres using Draper-Lin small composite design. Drug Des. Devel. Ther., 2016, 10, 825-839.
[http://dx.doi.org/10.2147/DDDT.S101900] [PMID: 26966353]
[19]
Vijayavani, S.C.; Vidyavathi, M. Azadirachita indica gum-based sildenafil citrate mucoadhesive microspheres – Design and optimization. J. Drug Deliv. Sci. Technol., 2018, 47, 499-513.
[http://dx.doi.org/10.1016/j.jddst.2018.08.011]
[20]
Rai, G.; Yadav, A.K.; Jain, N.K.; Agrawal, G.P. Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon. Drug Deliv., 2016, 23(1), 328-337.
[http://dx.doi.org/10.3109/10717544.2014.913733] [PMID: 24845476]
[21]
Ansari, M.; Sadarani, B.; Majumdar, A. Colon targeted beads loaded with pterostilbene: Formulation, optimization, characterization and in vivo evaluation. Saudi Pharm. J., 2019, 27(1), 71-81.
[http://dx.doi.org/10.1016/j.jsps.2018.07.021] [PMID: 30662309]
[22]
Sareen, R.; Jain, N.; Dhar, K.L. pH triggered delivery of curcumin from Eudragit-coated chitosan microspheres for inflammatory bowel disease: Characterization and pharmacodynamic evaluation. Drug Deliv., 2016, 23(1), 55-62.
[http://dx.doi.org/10.3109/10717544.2014.903534] [PMID: 24758141]
[23]
Khan, M.S.; Sridhar, B.K.; Srinatha, A. Development and evaluation of pH-dependent micro beads for colon targeting Indian J Pharm Sci., 2010, 72(1), 18-23.
[http://dx.doi.org/10.4103/0250-474X.62230] [PMID: 20582185]
[24]
Crystalline and Amorphous Solids. https://chem.libretexts.org/@go/page/6402

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy