Preparation and Evaluation of Nimesulide-loaded Ethylcellulose and Methylcellulose Nanoparticles and Microparticles for Oral Delivery

Abstract

The present study was designed to assess and compare with a range of surfactant-coated, nimesulide-free, and nimesulide-loaded ethylcellulose/methylcellulose (EC/MC) nanoparticles that were prepared by varying drug concentration (ED/MD), polymer concentration (EP/MP), and surfactant concentration (ES/MS). EC/MC nanoparticles prepared by desolvation method produced discrete particles and they were characterized by SEM, AFM, and FTIR studies. The particles mean size diameter (nm) ranged from 244 to 1056 nm and 1065 to 1710 nm for EC and MC nanoparticles, respectively. Studies on drug: polymer ratio showed a linear relationship between drug concentration and percentage of loading in nanoparticles. The encapsulation efficiency decreased with the increase of nimesulide concentration with respect to polymer concentration. Encapsulation efficiency of drug-loaded nanoparticles was varied between 32.8% and 64.9%. The in vitro release of drug-loaded nanoparticles was found to be a first order. This was significantly increased in EC nanoparticles (95.50%) in comparison with MC nanoparticles (95.12%) after 12 h in 24 h long study. Nimesulide release from EC nanoparticles was much slower at slightly alkaline pH 7.4. The in vitro hemolysis tests of nanoparticles were carried out to ascertain the hemocompatibility and shown to be insignificant for EC nanoparticles. In comparison, ES4 from EC formulations with nimesulide was found to be promising with slow and sustained drug release.

Keywords

ethylcellulose methylcellulose desolvation method drug encapsulation release efficiency hemolysis.

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References

Reddy, S.M. , Sinha, V.R. and Reddy, D.S. (1999). Oral Colon Specific Drug Delivery Systems for Pharmacotherapy of Peptide and Nonpeptide Drugs, Drugs Today , 35: 537-580.

Mehvar, R. (2000). Dextrans for Targeted and Sustained Delivery of Therapeutic and Imaging Agents, J. Cont. Release, 69(1): 1-25.

Kakoulidaes, E.P. , Smart, J.D. and Tsibouklis , J. (1998). Azo Crosslinked Poly(acrylic acid) for Colonic Delivery and Adhesion Specificity: In Vitro Degradation and Preliminarily Ex Vivo Bioadhesion Studies, J. Cont. Release, 54: 95-109.

Reynolds, J.E.F. (1999). Martindale: The Extra Pharmacopenia, 32nd edn, p. 63, The Pharmaceutical Press, London.

Budavari, S. (1996). The Merck Index, 12th edn, p. 6640, Merck & Co. Inc., Whitehouse Station, NJ.

Murthy, T.E.G.K. and Choudhary, P.R. (2005). Formulation and Evaluation of Ethyl Cellulose-coated Diclofenac Sodium Microcapsules: Influence of Solvents , Indian J. Pharm. Sci., 67(2): 216-219.

Geetha Rao, G.C. , Vijayanarayana , K. , Manojkumar, M.G. , Rashmi Roddrigues, S. , Sathyanarayana, D. and Subramanyam, E.V.S. (2005). Nimesulide Incorporated Lipid Microspheres: An Approach to Targeting and Controlled Release, Indian J. Pharm. Sci., 67(3): 292-296.

Yamuda, T. , Onishi, H. and Machida, Y. (2001). Sustained Release Ketoprofen Microparticles with Ethyl Cellulose and Carboxymethylethylcellulose, J. Cont. Release, 75: 271-282.

Kositza, M.J. , Bohne, C. , Alexandridis, P. , Hatton, T.A. and Holzwarth , J.F. (1999). Dynamics of Micro- and Macrophase Separation of Amphiphilic Block-copolymers in Aqueous Solution, Macromolecules, 32: 5539-5551.

10.

Lee, S.H. , Kim, S.H. and Kim, Y.H. (2002). Synthesis and Degradation Behaviors of PEO/PL/PEO Tri-block Copolymers, Macromol. Res. , 10: 85-90.

11.

Wu, C. , Liu, T. , Chu, B. , Schneider, D.K. and Graziano, V. (1997). Characterization of the PEO-PPO-PEO Triblock Copolymer and its Application as a Seperation Medium in Capillary Electrophoresis, Macromolecules, 30: 4574-4583.

12.

Yekta, A. , Xu, B. , Duhamel, J. , Adiwidjaja, H. and Winnik, M.A. (1995). Fluorescence Studies of Associating Polymers in Water: Determination of the Chain End Aggregation Number and a Model for the Association Process, Macromolecules, 28: 956-966.

13.

Yuan, M.L. , Wang, Y.H. , Li, X.H. , Xiong, C.D. and Deng, X.M. (2000). Polymerization of Lactides and Lactones: 10. Synthesis, Characterization, and Application of Amino-terminated Poly (ethylene glycol)-Co-Poly (q-caprolactone) Block Copolymer, Macromolecules, 33: 1613-1617.

14.

Zhao, Y. , Liang, H.J. , Wang, S.G. and Wu, C. (2001). Self-assembly of Poly(caprolactone-b-ethylene oxide-b-caprolactone) Via a Microphase Inversion in Water, J. Phys. Chem., B, 105: 848-851.

15.

Gan, Z.H. , Jim, T.F. , Li, M. , Yuer, Z. , Wang, S.G. and Wu, C. (1999). Enzymatic Biodegradation of Poly(ethylene oxide-b-q-caprolactone) Diblock Copolymer and its Potential Biomedical Applications, Macromolecules, 32: 590-594.

16.

Rosler, A. , Vandermeulen, G.W.M. and Klok, H.A. (2001). Advanced Drug Delivery Devices Via Self-assembly of Amphiphilic Block Copolymers, Adv. Drug Deliv. Rev., 53: 95-108.

17.

Santhi, K. , Venkatesh, D.N. , Dhanaraj, S.A. , Sangeetha, S. and Suresh, B. (2005). Development and In-vitro Evaluation of a Topical Drug Delivery System Containing Betamethazone Loaded Ethyl Cellulose Nanospheres, Trop. J. Pharm. Res., 4(2): 495-500.

18.

Discher, D.E. and Eisenberg, A. (2002). Polymer Vesicles, Science, 297: 967-973.

19.

Yu, K. , Bartels, C. and Eisenberg, A. (1998). Vesicles with Hollow Rods in the Walls: A Trapped Intermediate Morphology in the Transition of Vesicles to Inverted Hexagonally Packed Rods in Dilute Solutions of PS-b-PEO, Macromolecules , 31: 9399-9402.

20.

Xionga, X.Y. , Tamb, K.C. and Ganc, L.H. (2005). Effect of Enzymatic Degradation on the Release Kinetics of Model Drug from Pluronic F127/Poly(Lactic Acid) Nano-particles, J. Cont. Release, 108(2-3): 263-270.

21.

Davis, R. and Brogden, R.N. (1994). Nimesulide: An Update of its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Efficacy, Drugs , 48(3): 431-454.

22.

Meriani, F. , Coceani, N. , Sirotti, C. , Voinovich, V. and Grassi, M. (2003). Characterization of a Quaternary Liquid System Improving the Bioavailability of Poorly Water Soluble Drugs, J. Colloid. Interface Sci., 263: 590-596.

23.

Piel, G. , Pirotte, B. and Delneuveille, I. (1997). Study of the Influence of both Cyclodextrins and L-lysine on the Aqueous Solubility of Nimesulide: Isolation and Characterization of Nimesulide-L-lysine-cyclodextrin Complexes , J. Pharm. Sci., 86: 475-480.

24.

Ferreira, S.H. (1993). Role of Interleukins and Nitric Oxide in the Mediation of Inflammatory Pain and its Control by Peripheral Analgesics, Drugs, 46(1): 1-9.

25.

Tognella, S. (1993). Nimesulide: New Clinical Opportunities, Drugs, 46(1): 275-276.

26.

Verhoeven, A.J. , Tool, A.T.J. , Kuijpers, T.W. and Roos, D. (1993). Nimesulide Inhibits Platelet-activating Factor Synthesis in Activated Human Neutrophils, Drugs, 46(1): 52-58.

27.

Singla, A.K. , Chawla, M. and Singh, A. (2000). Nimesulide: Some Pharmaceutical and Pharmacological Aspects and Update, J. Pharm. Pharmacol. , 52: 467-486.

28.

Paul, A.I. (1996). In: Hardman, J.G., Limbird, L.E., Molinoff, P.B., Ruddon, W.R. and Gilman, A.G. (eds), Goodman and Gilman's The Pharmacological Basis of Therapeutics, Chapter ``Drugs Affecting Renal and Cardiovascular Function'', 9th edn, p. 644, McGraw-Hill Companies, Inc., New York.

29.

Chowdary, K.P.R. , Koteshwara Rao, N. and Malathi, K. (2004). Ethyl Cellulose Microspheres of Glipizide: Characterization, In Vitro and In Vivo Evaluation, Indian J. Pharm. Sci., 66: 412-416.

30.

Mukherji, G. , Murthy, R.S.R. and Miglani , B.D. (1990). Preparation and Evaluation of Cellulose Nanospheres Containing 5-flourouracil , Int. J. Pharm., 65: 1-5.