Research Article | Volume: 8, Issue: 11, November, 2018

Gastric floating in-situ gel as a strategy for improving anti-inflammatory activity of meloxicam

Mohammed Jafar Mohammed Salahuddin Srinivasa Rao Bolla   

Open Access   

Published:  Nov 30, 2018

DOI: 10.7324/JAPS.2018.81114
Abstract

The present study was aimed to develop gastric floating in-situ gels of meloxicam (MLX) mainly to enhance anti-inflammatory activity and alleviate gastric ulceration potential of meloxicam. Ternary inclusion complex of meloxicam containing hydrox ypropyl beta cyclodextrin (HPβCD) and diethylamine (DEA) in 1:1:1 molar ratio was used as a chief component in the development of gastric floating in-situ gel formulations of meloxicam. Box–Behnken design was utilized to design and optimize gastric floating in-situ gels of meloxicam. Independent variables (concentrations of sodium alginate, calcium carbonate, and a ternary inclusion complex of meloxicam, respectively) were optimized in order to achieve the desired responses. The response surface plots and the possible interactions between the independent variables were analyzed using the Design Expert Software 11.0.3.0 (Stat-Ease, Inc, USA). The results showed that the optimized gastric floating in-situ gels with a short floating lag time (41 seconds), low viscosity (190 cps), and high in vitro drug release at sixth hour (77%) was obtained using an optimized combination of calcium carbonate (0.75% w/v), sodium alginate (1.25% w/v), and MLX-HPβCD-DEA ternary complex (equivalent to 11.25 mg of meloxicam), respectively. Moreover, the optimized gastric floating in-situ gel formulation of meloxicam ternary complex exhibited significantly ameliorated anti-inflammatory activity [84.38% (p < 0.05) at sixth hour and also showed a significant reduction in local gastric ulceration potential compared to pure meloxicam]. Thus, this gastric floating in situ gelling system can be translated for existing and established non-steroidal anti-inflammatory drugs (NSAID) as well as formulations.


Keyword:     Meloxicam inclusion complex NSAID in-situ gel in vivo activity.


Citation:

Jafar M, Salahuddin M, Bolla SR. Gastric floating in-situ gel as a strategy for improving anti-inflammatory activity of meloxicam. J App Pharm Sci, 2018; 8(11): 095–102.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Reference

Alam S, Aslam M, Khan A, Imam SS, Aqil M, Sultana Y, Ali A. Nanostructured lipid carriers of pioglitazone for transdermal application: from experimental design to bioactivity detail. Drug Deliv, 2016; 23(2):601–9.
https://doi.org/10.3109/10717544.2014.923958

Awasthi SS, Kumar TG, Manisha P, Preeti Y, Kumar SS. Development of meloxicam formulations utilizing ternary complexation for solubility enhancement. Pakistan J Pharm Sci, 2011; 24(4):533–8.

Belhadji L, HadjSadok A, Moulai-Mostefa N. Design and characterization of calcium-free in-situ gel formulation based on sodium alginate and chitosan. Drug Develop Indus Pharm, 2017; 44(4):662–9.
https://doi.org/10.1080/03639045.2017.1408640

Box GEP, Wilson KB. On the experimental attainment of multifactorial conditions. J Royal Statis Soc, 1951; 13:1–12.

El-Kamel AH, Sokar MS, Al-Gamal SS, Naggar VF. Preparation and evaluation of ketoprofen floating oral delivery system. Int J Pharm,2001; 220:13–21.
https://doi.org/10.1016/S0378-5173(01)00574-9

Ghare JL, Mundada AS. Evaluation of novel polymer in the development of floating in situ gelling system. J Appl Pharm Sci, 2017;9:238.
https://doi.org/10.21065/1920-4159.1000238

Gowthamarajan K, Giriraj Kulkarni T, Venkateswaran G, Samanta MK, Suresh B. Formulation and dissolution properties of meloxicam solid dispersion incorporated suppositories. Indian J Pharm Sci,2002; 64(6):525–8.

Jafar M, Ali S. Studies on meloxicam solid dispersion incorporated buccal patches. Int Res J Pharm, 2011; 2(5):220–7.

Jafar M, Salahuddin M, Kayed TS, Ahmad N, Al-Eid HA, Al-Qarros AH. Buoyant in situ gels of meloxicam-[beta]-cyclodextrintriethanolamine ternary complex for oral delivery; from a box-behnken experimental design to in vivo activity detail. Asian J Chem, 2017;29(6):1275–84.

Jafar M, Salahuddin M, Kayed TS, Ahmad N, Al-Eid HA, Al-Qarross AH. Solid state analysis and in-vitro dissolution behavior of meloxicam-hydroxy propyl beta cyclodextrin-ethanolamines ternary complexes. Int J Pharm Qual Assurance, 2018; 9(1):80–6.

Kerdsakundee N, Wiwattanapatapee R, Mahattanadul S. Floating gellan gum-based in situ gels containing curcumin for specific delivery to the stomach. Thai J Pharm Sci, 2016; 40(Suppl):33–6.

Kubo W, Miyazaki S, Attwood D. Oral sustained delivery of paracetamol from in situ-gelling gellan and sodium alginate formulations.Int J Pharm, 2003; 258:55–64
https://doi.org/10.1016/S0378-5173(03)00163-7

Mishra DN, Vijay Kumar SG. Investigations on analgesic, anti-inflammatory and ulcerogenic potential of meloxicam solid dispersion prepared with skimmed milk. Yakugaku Zasshi, 2006; 126(7):495–8.
https://doi.org/10.1248/yakushi.126.495

Miyazaki S, Kawasaki N, Kubo W, Endo K, Attwood D. Comparison of in situ gelling formulations for the oral delivery of cimetidine. Int J Pharm, 2001; 220(1–2):161–8.
https://doi.org/10.1016/S0378-5173(01)00669-X

Prabaharan M, Mano JF. Stimuli-responsive hydrogels based on polysaccharides incorporated with thermo-responsive polymers as novel biomaterials. Macromol Biosci, 2006; 6(12):991–1008.
https://doi.org/10.1002/mabi.200600164

Rajinikanth PS, Balasubramaniam J, Mishra B. Development and evaluation of a novel floating in situ gelling system of amoxicillin for eradication of Helicobacter pylori. Int J Pharm, 2007; 335(1–2):114–22.
https://doi.org/10.1016/j.ijpharm.2006.11.008

Rajinikanth PS, Mishra B. Stomach-site specific drug delivery system of clarithromycin for eradication of Helicobacter pylori. Chem Pharma Bull, 2009; 57(10):1068–75.
https://doi.org/10.1248/cpb.57.1068

Rouge N, Buri P, Doelkar E. Drug absorption sites in the gastrointestinal tract and dosage forms for site-specific delivery. Int J Pharm, 1996; 136(1–2):117–39.
https://doi.org/10.1016/0378-5173(96)85200-8

Samprasit W, Akkaramongkolporn P, Ngawhirunpat T,Rojanarata T, Opanasopit P. Formulation and evaluation of meloxicam oral disintegrating tablet with dissolution enhanced by combination of cyclodextrin and ion exchange resins. Drug Develop Indus Pharm, 2015;41(6):1006–16.
https://doi.org/10.3109/03639045.2014.922573

Sharma A, Sharma J, Kaur R, Saini V. Development and characterization of in-situ oral gel of spiramycin. BioMed Res Int, 2014;876182.

Shendge RS, Jamdhade AA, Pande VV. Novel strategy in controlled gastroretentive drug delivery: in-situ floating gel. Int J Drug Delivery, 2014; 6:230–43.

Thanoo BC, Sunny MC, Jayakrishnan A. Oral sustained-release drug delivery systems using polycarbonate microspheres capable of floating on the gastric fluid. J Pharm Pharmacol, 1993; 45(1):21–4.
https://doi.org/10.1111/j.2042-7158.1993.tb03672.x

Winter CA, Risley EA, Silber RH. Antiinflammatory activity of indomethacin and plasma corticosterone in rats. J Pharmacol Exp Ther,1968; 162:196–201.

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