PREPARATION, CHARACTERIZATION AND EVALUATION OF ANTI-INFLAMMATORY ACTIVITY OF ETORICOXIB LOADED SOLUPLUS® NANOCOMPOSITES


Yogesh Pore, Madhuri Mane, Vaishnavi Mangrule, Atul Chopade, Pankaj Gajare

Abstract


Objective: The objective of this study was to prepare and characterize etoricoxib (ECB) loaded Soluplus® nanocomposites to improve its physicochemical properties. The effect of polymer and surfactant concentration on particle size, in vitro percentage dissolution efficiency and the anti- inflammatory activity of nanocomposites were also investigated.

Methods: The nanocomposites were prepared by using a freeze drying technique. The analytical evidences for formulation of lyophilized nanocomposites in solid state were generated and confirmed by differential scanning calorimetry (DSC), fourier transformation infrared spectroscopy (FTIR), x-ray powder diffractometry (XPRD) and scanning electron microscopy (SEM). The in vitro drug release profile of nanocomposites was compared with pure ECB powder.

Results: The nanocomposites of ECB were ontained in a nano range with particle size and zeta potential of 63.5 nm and 46.5 mv, respectively. The solubility and dissolution of the nanocomposites were significantly (p < 0.001) improved as compared to ECB alone, evidenced by decreased log P values (1.90 ± 0.002) of the nanocomposites. The characterization studies revealed formation of amorphous nanocomposites of ECB with existence of physical interactions between drug and polymer. The anti- inflammatory activity of nanocomposites evaluated by carrageenan induced rat paw edema model demonstrated non significant (p > 0.05) increase in anti- inflammatory activity as compared to pure ECB.

Conclusion: From the results, it could be concluded that the formation of ECB nanocomposites with Soluplus® could be an effective and alternative approach to modify physicochemical properties of ECB.   


Keywords


Etoricoxib; Soluplus®; nanocomposites; physicochemical properties; anti- inflammatory activity

References


Chowdary KPR, Rao KSP and Madhuri D. Formulation and evaluation of etoricoxib tablets employing cyclodextrin-poloxamer 407-PVP K 30 inclusion complexes. Int J Appl Biol Pharm 2011; 2: 43-48.

Raja RK, Abbulu K, Sudhakar M, Vishwanadham M, Syama MT. Studies on dissolution enhancement of Lovaststin using soluplus by solid dispersion technique. Int J Pharm Pharm Sci 2012; 4: 124-28.

Kasar PM, Kale KS, Phadtare DP. Nanoplex: A review of nanotechnology approach for solubility and dissolution rate enhancement. Int J Curr Pharm Res 2018; 10: 6- 10.

Amidon GL, Lennernas H, Shaha VP, Crison JR. A theoretical basis for biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995; 12: 413-20.

Patel RN, Bahareh M, Patel S. Modification of physical and chemical properties of BCS II Drug. Int J Pharm Pharm Sci 2012; 4: 290-02.

Muralidhar SM, Rao GD, Murthy MK, Kumar KK, Teja KK, Nawaj S, Narayana TV. Enhancement of dissolution rate of etoricoxib through solid dispersion technique. J appl Pharm Sci 2011; 1: 129-32.

Cochrane DJ, Jarvis B, Keating GM. Etoricoxib. Drugs. 2002; 62: 2637-51.

Schott H, Kwan LC, Feldman S. The role of surfactant in the release of very slightly soluble drugs from tablets. J Pharm Sci 1982; 71: 1038-42.

Veiga F, Teixeria- Dias JJC, Kedzeierewicz F, Sousa A, Maincent P. Inclusion complexation of tolbutamide with β- cyclodextrin and hydroxypropyl- β- cyclodextrin. Int J Pharm 1996; 129: 63-71.

Longxiao L, Suyan Z. Preparation and characterization of inclusion complexes of prazosin hydrochloride with β- cyclodextrin and hydroxypropyl- β- cyclodextrin. J Pharm Biomed Anal 2006; 28: 122-27.

Henck JO, Griesser UJ, Burger A. Polymorphie von Arzneistoffen Eine wirtschaftliche Herausforderung. Pharm India 1997; 59: 165-69.

Hancock BC, Zografi G. Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci 1997; 86: 1- 12.

Chiou WL, Riegelman S. Pharmaceutical applications of solid dispersion systems. J Pharm Sci 1971; 60: 1281- 02.

Serajuddin ATM. Solid dispersion of poorly water- soluble drugs: Early promises, subsequent problems, and recent break- throughs. J Pharm Sci 1999; 88: 1058- 66.

Patnaik S, Aditha SK, Rattan T, Kamisetti V. Aceclofenac- Soluplus® Nanocomposites for increased bioavailability.SNL 2015; 5: 13-20.

BASF. Technical Information soluplus, BASF. Pharm Ingredients and Services. 2010; 1-8.

Agrawal NGB, Porras AG. Dose proportionality of oral etoricoxib, a highly selective cyclooxygenase-2 inhibitor, in healthy volunteers. J. Clin Pharmacol; 2001; 41: 1106-10.

Rodrigues AD, Halpin RA, Geer LA. Absorption, metabolism, and excretion of etoricoxib, a potent and selective cyclooxygenase-2 inhibitor, in healthy male volunteers. Drug Metab Dispos. 2003; 31: 224-32.

Suhagia BN, Patel HM, Shah SA, Rathod I, Parmar VK. Preparation and characterization of etoricoxib-polyethylene glycol 4000 plus polyvinylpyrrolidone k30 solid dispersions. Acta Pharm 2006; 56: 285-98.

Chauhan B, Shimpi S, and Paradkar A. Preparation and Characterization of Etoricoxib Solid Dispersions Using Lipid Carriers by Spray Drying Technique. AAPS pharm Sci tech 2005; 6: E405-12.

Karekar P, Vyas V, Shah M, Sancheti P, Pore YV. Physicochemical investigation of the solid dispersion systems of etoricoxib with poloxamer 188. Pharm Dev Tech 2009; 14: 373-79.

Shimpi SL, Chauhan B, Mahadik KR, and Paradkar A. Stabilization and Improved in Vivo Performance of Amorphous Etoricoxib using Gelucire 50/13. Pharm Res 2005; 22: 1727-34.

Shimpi SL, Mahadik KR, Paradkar AR. Study on Mechanism for Amorphous Drug Stabilization Using Gelucire 50/13. Chem Pharm Bull 2009; 57: 937- 942.

Shimpi S, Mahadik K, Takada K, and Paradkar K. Application of Polyglycolized Glycerides in Protection of Amorphous Form of Etoricoxib during Compression. Chem Pharm Bull 2007; 55: 1448-51.

Shah M, Karekar P, Sancheti P,Vyas V, and Pore Y. Effect of PVP K30 and / or L-arginine on stability constant of etoricoxib-HP--CD inclusion complex: Preparation and characterization of etoricoxib-HP--CD binary system. Drug Dev Ind Pharm 2009; 35:118-29.

Patel HM, Suhagia BN, Shah SA, Rathod I, Parmar VK. Preparation and characterization of etoricoxib-β-cyclodextrin complexes prepared by the kneading method. Acta Pharm 2007; 57: 351-59.

Dash R, Acharya AK, Swain S, Barg M, Choudhary HK, Meher K. Formulation and Evaluation of Spherical Crystal of Etoricoxib. Int J Pharm & Bio Archives 2011; 2:1123-29.

Higuchi T, Connors K. Phase solubility techniques. Adv Anal Chem Instr 1965; 4: 117-12.

Desai PS, Pore YV. Physicochemical characterization of spray dried cefixime polymeric nanoparticles using factorial design approach. J Appl Pharm Sci 2016; 6: 124-32.

Khade S, Pore YV. Formulation and evaluation of neusiln® US2 adsorbed amorphous solid self- microemulsifying delivery system of atorvastatin calcium. Asian J Pharm Clin Res 2016; 9: 1-8.

Jadhav P, Pore YV. Physicochemical, thermodynamic and analytical studies on binary and ternary inclusion complexes of bosentan with hydroxypropyl-β- Cyclodextrin. Bull Fac Pharm (Cairo Univ) 2016; 55: 147-54.

Naidu G, Madhavi E, Konda VGR, Ramana V. Comparative study of anti- inflammatory activity of newer macrolides with etoricoxib. J E M Ds 2014; 3: 2413- 19.

Ferrero- Milianni L, Nielsen OH, Andersen PS. Chronic inflammation: importance of NOD2 and NALP3 in interleukin – l beta generation. Clin Exp Immunol 2007; 147: 227-35.

Mishara D, Ghosh G, Kumar P, Panda P. Anti- inflammatory and antipyretic activity of selective COX-2 inhibitor with conventional NSAIDS. Int J Pharm Sci Res 2010; 1: 103- 9.

Jafar M, Mhg D, Shareef A. Enhancement of dissolution and anti-inflammatory effect of meloxicam using solid dispersion. Int J App Pharm 2010; 2: 22- 27.

Niazi J, Gupta V, Chakarborty P, Kumar P. Anti-inflammatory and antipyretic activity of aleuritis moluccana leaves. Asian J Pharm Clin Res 2010; 3: 35- 36.

Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol 1975; 27: 48-49.

Mooter G, Augustijins, Blaton N, Kinget R. Physico- chemical characterization of solid dispersions of temazepam with polyethylene glycol 6000 and PVP K30. Int J Pharm 1998; 164: 67-80.

Ruan LP, Yu BY, Fu GM, Zhu D. Improving the solubility of ampelopsin by solid dispersions and inclusion complexes. J Pharm Biomed Anal 2005; 38: 457-64.

Bhosale P, Pore YV, Sayyad F. Preparation of amorphous carvedilol polymeric microparticles for improvement of physicochemical properties. J Pharm Investig 2012; 42 : 335-44.




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