Funct. Mater. 2015; 22 (4): 535-542.

http://dx.doi.org/10.15407/fm22.04.535

Effect of different particle size reduction techniques on the nefopam and aciclovir dispersity

N.A.Pinchukova1, N.A.Lyapunov1, E.P.Bezuglaya1, A.Yu.Voloshko1, A.N.Lyapunov1, M.A.Merko2, V.A.Chebanov1,2

[1] SSI "Institute for Single Crystals", National Academy of Sciences of Ukraine, 60 Lenin Ave., 61001 Kharkiv, Ukraine
[2] V.Karazin Kharkiv National University, 4 Svobody Sq., 61022 Kharkiv, Ukraine

Abstract: 

Presents the results of application of different particle size reduction approaches to the drug substances - aciclovir and nefopam, namely, wet milling, ultrasonic (US) dispergation, US crystallization and US antisolvent precipitation. All ultrasonic experiments were performed at two operation frequencies - 22 and 44 kHz. It was shown that the crucial parameters in US processes were US output power and sonication time, while the US frequency had a minor effect within the studied power range. US antisolvent precipitation showed the best results among the applied techniques yielding micron-sized particles of aciclovir, which makes this method a very promising technique in nanocrystallization area. The obtained study results provide an opportunity to choose the optimal particle reduction technique depending on the necessary particle size of drug substance suitable for a particular dosage form.

Keywords: 
particle size reduction, ultrasound dispergation, wet milling, crystallization, drug substance.
References: 

1. A.I.Rusanov, Phase Equilibria and Surface Phenomena, Khimija, Leningrad (1967) [in Russian].

2. A.Dokoumetzidis, P.Macheras, Int. J. Pharm., 321, 1 (2006). http://dx.doi.org/10.1016/j.ijpharm.2006.07.011

3. J.Zhang, L.Wu, H.-K.Chan, Adv. Drug Delivery Rev., 63, 441 (2011). http://dx.doi.org/10.1016/j.addr.2010.11.002

4. D.Thassu, M.Deleers, Y.Pathak, Nanoparticulate Drug Delivery Systems, Informa Healthcare USA, Inc., New York (2007). http://dx.doi.org/10.1201/9781420008449

5. C.Sun, D.Xue, Curr. Opin. Chem. Eng., 1, 108 (2012). http://dx.doi.org/10.1016/j.coche.2011.12.003

6. J.-U.A.H.Junghanns, R.H.Muller, Int. J. Nanomed., 3, 295 (2008).

7. H.Chen, C.Khemtong, X.Yang et al., Drug Discovery Today, 16, 354 (2011). http://dx.doi.org/10.1016/j.drudis.2010.02.009

8. F.Kesisoglou, S.Panmai, Y.Wu, Adv. Drug Delivery Rev., 59, 631 (2007). http://dx.doi.org/10.1016/j.addr.2007.05.003

9. G.D.Wang, F.P.Mallet, F.Ricard, J.Y. Heng, Curr. Opin. Chem. Eng., 1, 102 (2012). http://dx.doi.org/10.1016/j.coche.2011.12.001

10. H.de Waard, N.Grasmeijer, W.L.J.Hinrichs et al., Eur. J. Pharm. Sci., 38, 224 (2009). http://dx.doi.org/10.1016/j.ejps.2009.07.005

11. T.Panagiotou, S.V.Mesite, R.J.Fisher, Ind. Eng. Chem. Res., 48, 1761 (2009). http://dx.doi.org/10.1021/ie800955t

12. A.Harter, L.Schenck, I.Lee, A.Cote, Org. Process Res. Dev., 17, 1335 (2013). http://dx.doi.org/10.1021/op4001143

13. J.Salazar, R.H.Muller, J.P.Moschwitzer, J. Pharmac., 2014, 2014 (2014), Article ID 265754.

14. M.D.Luque de Castro, F.Priego-Capote, Ultrason. Sonochem., 14, 717 (2007). http://dx.doi.org/10.1016/j.ultsonch.2006.12.004

15. A.Kordylla, T.Krawczyk, F.Tumakaka, G.Schembecker, Chem. Eng. Sci., 64, 1635 (2009). http://dx.doi.org/10.1016/j.ces.2008.12.030

16. J.Dodds, F.Espitalier, O.Louisnard et al., Part. Part. Syst. Charact., 24, 18 (2007). http://dx.doi.org/10.1002/ppsc.200601046

17. G.Ruecroft, D.Hipkiss, T.Ly et al., Org. Process Res. Dev., 9, 923 (2005). http://dx.doi.org/10.1021/op050109x

18. J.Jordens, B.Gielen, L.Braeken, T.Van Gerven, Chem. Eng. Process, 84, 38 (2014). http://dx.doi.org/10.1016/j.cep.2014.01.006

19. State Ukrainian Pharmacopoeia, 1st Ed., Annex 2, State Enterprise "Scientific-Advisory Pharmacopoeian Centre", Kharkiv (2008) [in Ukrainian].

20. Thechnical Guide for the Elaboration of Monographs. 4th Ed. European Pharmacopoeia, European Directorate for the Quality of Medicines (2005).

21. Validation of Analytical Procedures: Text And Methodology Q2(R1) - ICH Harmonised Tripartite Guideline, Retrieved from the Intern. Conf. on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, San Diego, USA (2014).

Current number: