Nanonization of Niflumic Acid by Co-Grinding
ABSTRACT
The aim of this study was to produce niflumic acid nanoparticles without using an organic solvent, in order to achieve an increased rate of dissolution of the final products. Co-grinding with excipients was used to decrease the particle size. Poloxamer 188 (P) and mannitol (M) applied as co-grinding materials stabilized the system, preventing aggregation of the nanocrystals. The morphology and particle size distribution of the products were visualized by using scanning electron microscopy and laser diffraction. The crystalline states of the samples were investigated by differential scanning calorimetry and X-ray powder diffraction. The rate of dissolution of niflumic acid was measured with a paddle method from simulated media. It was concluded that the particles produced were in the nanometer range (the mean particle size was ~250 nm) and the nanoparticles maintained their crystallinity during the process. The rate of dissolution of the coground sample was significantly improved.
Cite this paper
Szunyogh, T. , Ambrus, R. and Szabó-Révész, P. (2013) Nanonization of Niflumic Acid by Co-Grinding. Advances in Nanoparticles, 2, 329-335. doi: 10.4236/anp.2013.24045.
Szunyogh, T. , Ambrus, R. and Szabó-Révész, P. (2013) Nanonization of Niflumic Acid by Co-Grinding. Advances in Nanoparticles, 2, 329-335. doi: 10.4236/anp.2013.24045.
References
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[1] Y. Kawabata, K. Wada, M. Nakatani, S. Yamada and S. Onoue, “Formulation Design for Poorly Water-Soluble Drugs Based on Biopharmaceutics Classification System: Basic Approaches and Practical Applications,” International Journal of Pharmaceutics, Vol. 420, No. 1, 2011, pp. 1-10. http://dx.doi.org/10.1016/j.ijpharm.2011.08.032 [2] A. A. Noyes and W. R. Whitney, “The Rate of Solution of Solid Substances in Their Own Solution,” Journal of the American Chemical Society, Vol. 19, No. 12, 1897, pp. 930-934. http://dx.doi.org/10.1021/ja02086a003 [3] J-U. A. H. Junghans and R. H. Müller, “Nanocrystals Technology, Drug Delivery and Clinical Applications,” International Journal of Nanomedicine, Vol. 3, No. 3, 2008, pp. 295-309. http://dx.doi.org/10.2147/IJN.S595 [4] G. G. Liversidge and P. Conzentino, “Drug Particle Size Reduction for Decreasing Gastric Irritancy and Enhancing Absorption of Naproxen in Rats,” International Journal of Pharmaceutics, Vol. 125, No. 2, 1995, pp. 309-313.
http://dx.doi.org/10.1016/0378-5173(95)00148-C [5] P. Liu, X. Rong, J. Laru, J. Veen, B. Kiesvaara, J. Hiruonen, T. Laaksonen and L. Peltonen, “Nanosuspensions of Poorly Soluble Drugs: Preparation and Development by Wet Milling,” International Journal of Pharmaceutics, Vol. 411, No. 1-2, 2011, pp. 215-222.
http://dx.doi.org/10.1016/j.ijpharm.2011.03.050 [6] R. H. Müller and A. Akkar, “Drug Nanocrystals of poorly Soluble Drugs,” Encyclopedia of Nanoscience and Nanotechnology, Vol. 62, No. 1, 2004, pp. 627-638. [7] P. Kocbek, S. Baumgartner and J. Kristl, “Preparation and Evaluation of Nanosuspension for Enhancing the Dissolution of Poorly Soluble Drugs,” International Journal of Pharmaceutics, Vol. 312, No. 1-2, 2006, pp. 179-186.
http://dx.doi.org/10.1016/j.ijpharm.2006.01.008 [8] J. Hecq, M. Deleers, D. Fanara, H. Vranckx and K. Amighi, “Preparation and Characterization of Nanocrystals for Solubility and Dissolution Rate Enhancement of Nifedipine, ” International Journal of Pharmaceutics, Vol. 299, No. 1-2, 2005, pp. 167-177.
http://dx.doi.org/10.1016/j.ijpharm.2005.05.014 [9] T. Yasuji, H. Takeuchi and Y. Kawashima, “Particle Design of Poorly Water-Soluble Substances Using Supercritical Fluid Technologies,” Advanced Drug Delivery Reviews, Vol. 60, No. 3, 2008, pp. 388-398.
http://dx.doi.org/10.1016/j.addr.2007.03.025 [10] M. Sarkari, J. Brown, X. Chen, S. Swinnea, R. O. Williams and K. P. Johnston, “Enhanced Drug Dissolution Using Evaporative Precipitation into Aqueous Solution,” International Journal of Pharmaceutics, Vol. 243, No. 1-2, 2002, pp. 17-31.
http://dx.doi.org/10.1016/S0378-5173(02)00072-8 [11] J. Chingunpituk, “Nanosuspension Technology for Drug Delivery,” Walailak Journal of Science and Technology, Vol. 4, No. 2, 2007, pp. 139-153. [12] R. Ravichandran, “Nanotechnology-Based Drug Delivery System,” Nanobiotechnology, Vol. 5, No. 1-4, 2009, pp. 17-33. http://dx.doi.org/10.1007/s12030-009-9028-2 [13] L. Kürti, á. Kukovecz, G. Kozma, R. Ambrus, M. A. Deli and P. Szabó-Révész, “Study of the Parameters Influencing the Co-Gringing Process for the Production Meloxicam Nanoparticles,” Powder Technology, Vol. 212, No. 1, 2012, pp. 210-217.
http://dx.doi.org/10.1016/j.powtec.2011.05.018 [14] Y. S. Thorat, I. D. Gonjari and A. H. Hosani, “Solubility Enhancement Techniques: A Review on Conventional and Novel Approaches,” International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 2, No. 10, 2011, pp. 2501-2513. [15] S. Budavari, “The Merck Index,” 11th Edition, Merck & Co., Rahway, New York, 1989. [16] M. William, “The Extra Pharmacopoeia,” 31st Edition, Royal Pharmaceutical Society, London, 1996. [17] M. Kata, R. Ambrus and Z. Aigner, “Preparation and Investigation of Inclusion Complexes Containing Niflumic Acid and Cyclodextrins,” Journal of Inclusion Phenomena and Macrocyclic Chemistry, Vol. 44, No. 1-4, 2002, pp. 123-126.
http://dx.doi.org/10.1023/A:1023074025175 [18] R. Ambrus, Z. Aigner, L. Catenacci, G. Bettinetti, P. Szabó-Révész and M. Sorrenti, “Physico-Chemical Characterization and Dissolution Properties of Niflumic AcidCyclodextrin-PVP Ternary Systems,” Journal of Thermal Analysis and Calorimetry, Vol. 104, No. 1, 2011, pp. 291-297. http://dx.doi.org/10.1007/s10973-010-1069-1 [19] R. Ambrus, Z. Aigner, C. Dehelean, C. Soica and P. Szabó-Révész, “Physico-Chemical Studies on Solid Dispersions of Niflumic Acid Prepared with PVP,” Revista de Chimie, Vol. 58, No. 1, 2007, pp. 60-64. [20] R. Ambrus, Z. Aigner, C. Soica, C. Peev and P. SzabóRévész, “Amorphisation of Niflumic Acid with Polyvinylpyrrolidone Prepared Solid Dispersion to Reach Rapid Drug Release,” Revista de Chimie, Vol. 58, No. 2, 2007, pp. 206-209. [21] T. Szunyogh, R. Ambrus and P. Szabó-Révész, “Formation of Niflumic Acid Particle Size by Solvent Diffusion and Solvent Evaporation as Precipitation Method,” Journal of Drug Delivery Science and Technology, Vol. 22, No. 4, 2012, pp. 307-312. [22] T. Szunyogh, R. Ambrus and P. Szabó-Révész, “Importance of Particle Size Decrease in the Preformulation,” Acta Pharmaceutica Hungarica, Vol. 81, No. 1, 2011, pp. 29-36. [23] A. Jaworek, “Microand Nanoparticle Production by Electrospraying,” Powder Technology, Vol. 176, No. 1, 2007, pp. 18-35.
http://dx.doi.org/10.1016/j.powtec.2007.01.035 [24] R. Ambrus, N. Radacsi, T. Szunyogh, A. E. D. M. Van Der Heijden, J. H. Ter Horst and P. Szabó-Révész, “Analysis of Submicron-Sized Niflumic Acid Crystals Prepared by Electrospray Crystallization,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 76, 2013, pp. 1-7. http://dx.doi.org/10.1016/j.jpba.2012.12.001 [25] N. Radacsi, R. Ambrus, T. Szunyogh, A. I. Stankiewicz, A.E.D.M van der Heijden and J. H. ter Horst, “Electrospray Crystallization for Nano-Sized Pharmaceuticals with Improved Properties,” Crystal Growth & Design, Vol. 12, No. 7, 2012, pp. 3514-352.
http://dx.doi.org/10.1021/cg300285w [26] M. Wagner, “Thermal Analysis in Practice,” DSC Evaluations, Schwerzenbach, 2009, pp. 90-141.