FORMULATION, OPTIMIZATION AND CHARACTERIZATION OF ZIPRASIDONE NANOCRYSTALS PREPARED BY MEDIA MILLING TECHNIQUE
Objective: Today, nanotechnology has a variety of application areas. Pharmacy is one of the most important application fields of nanotechnology. Preparation of nano-particular drug-delivery system, such as nano-crystals improve the solubility and bio-availability of poorly water soluble drugs.
Methods: Ziprasidone (ZIP) is a low water soluble drug (Bio-pharmaceutical classification system) and is used as a lipid regulating agent. In this study, a rapid and simple media milling method was used for the preparation of ziprasidone (ZIP) Nanocrystals. The use of sonication after media milling process reduced the milling time significantly. Different concentrations of stabilizers (Kollidone and Tween 80) were tested in the preparation of ZIP nanocrystals. The finest ZIP nanocrystals were obtained by 4 g ZIP, 4 g kollidone and 4 g Tween 80.
Results: The size and zeta potential of the finest ZIP nanocrystals were 238.2Â±2.5 nm and-19.6Â±0.1 mv, respectively. The morphology of dried ZIP nanocrystals was observed using scanning electron microscopy. Differential scanning calorimetry of ZIP and ZIP nanocrystals confirmed that there was no interaction between ZIP and stabilizers. Compared with ZIP, the solubility of ZIP nanocrystals increased significantly.
Conclusion: Media milling technology was successfully used for the formulation of poor water soluble drugs. Nano-sized drug particles prepared by media milling technique could improve the solubility and bio-availability of those drugs.
2. Muller RH, Peters K. Nanosuspension for the formulation of poorly soluble drugs: I. Preparation by a size reduction technique. Int J Pharm 1998;160:229-37.
3. Chaudhary A, Nagaich U, Gulati N, Sharma VK, Khosa RL. Enhancement of solubilization and bio-availability of poorly soluble drugs by physical and chemical modification: a recent review. J Adv Pharm Educ Res 2012;2:32-67.
4. Jinno J, Kamada N, Miyake M, Yamada K, Mukai T, Odomi M, et al. Effect of particle size reduction on dissolution and oral absorption of a poorly water-soluble drug, cilostazol, in beagle dogs. J Controlled Release 2006;111:56-64.
5. Bhalekar MR, Upadhaya PG, Reddy S, Kshirsagar SJ, Madgulkar AR. Formulation and evaluation of acyclovir nanosuspension for enhancement of oral bio-availability. Asian J Pharm 2014;8:110-8.
6. Mokale V, Patil K, Khatik T, Sutar Y. Glyburide nanosuspe NCion: Influence of processing and formulation parameter on solubility andin vitro dissolution behavior. Asian J Pharm 2013;7(3):111-7.
7. Bastami Z, Taheri A, Soltanpour S. Formulation, optimization and characterization of gemfibrozil Nanocrystals prepared by wet milling technique. Asian J Pharm 2015;9:19-22.
8. The Merck Index, Merck Research Laboratories, Division of Merck and co, Inc, N J; 2009. p. 763, 644.
9. Peter K, Leitzke S, Diederiches JE, Borner K, Hahn H, Muller RH, et al. Preparation of clofazamine nanosuspention for intravenous use and evalution of its therapeutic efficacy in murine Mycobactrrium avium infection. J Antimicrob Chemother 2000;45:77-83.
10. Zhang X, Xia Q, Gu N. Preparation of all-trans retinoic acid nanosuspentions using a modified precipitation method. Drug Dev Ind Pharm 2000;32:857-63.
11. Rogers TL, Gillespie IB, Hitt JE, Fransen KL, Crowl CA, Tucker CJ, et al. Development and characterization of a scalable controlled precipitation process to enhance the dissolution of poorly water-soluble drugs. Pharm Res 2004;21:2048-57.
12. Mittapalli PK, Yamasani MR, Shashank A. Improved bio-availability of albendazole following oral administration of nanosuspension in rats. Curr Nanosci 2007;3:191-4.
13. Chan HK, Chew NY. Novel alternative methods for the delivery of drugs for the treatment of asthma. Adv Drug Delivery Rev 2003;55:793-805.
14. MÃ¶schwitzer J, MÃ¼ller RH. New method for the effective production of ultrafine drug Nanocrystals. J Nanosci Nanotechnol 2006;6:3145-53.
15. MÃ¼ller RH, Jacobs C, Kayser O. Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future. Adv Drug Delivery Rev 2001;47:3-19.
16. Teeranachaideekul V, Junyaprasert VB, Souto EB, MÃ¼ller RH. Development of ascorbyl palmitate Nanocrystals applying the nanosuspension technology. Int J Pharm 2008;354:227-34.