NANOCRYSTAL SUSPENSION OF CEFIXIME TRIHYDRATE PREPARATION BY HIGH-PRESSURE HOMOGENIZATION FORMULATION DESIGN USING 23 FACTORIAL DESIGN
Objective: In the present study, nanocrystal suspensions of cefixime trihydrate were prepared with the objective of providing increased solubility and stability with their nanoscopic size and thus developing the formulation of enhanced bioavailability potential.
Methods: Nanocrystal suspensions were prepared by high-pressure homogenization technique using PVP K-30 as a stabilizer and evaluated for particle size, polydispersity index, zeta potential, permeation and drug release.
Results: Particles of average size 143.5 nm having a polydispersity index of 0.269 were produced. Zeta potential was found to be âˆ’36.6 mV and the formulation was found stable on the basis of results obtained from differential scanning calorimetry and Fourier transform infrared spectroscopy studies. Optimized formulation showed 89.79 % and 88.38% drug lease and permeation respectively.
Conclusion: The drug release and ex-vivo permeation studies revealed enhanced permeation of drug, as desired, indicating its potential for an attempt towards successful nano crystal formulation.
2. Maraie NK, T Alhamdany AN, Radhi AA. Efficacy of combination solid dispersion technology on dissolution performance of nalidixic acid and cefdinir. Asian J Pharm Clin Res 2017;10:394-401.
3. Rabinow BE. Nanosuspensions in drug delivery. Nature Rev Drug Discovery 2004;3:785-96.
4. Valeh-e-Sheyda P, Rahimi M, Adibi H, Razmjou Z, Ghasempour H. An insight on reducing the particle size of poorly-water soluble curcumin via LASP in micro channels. Chem Eng Proc: Process Intensification 2015;91:78-88.
5. Han HK, Choi HK. Improved absorption of meloxicam via salt formation with ethanolamines. Eur J Pharm Biopharm 2007;65:99-103.
6. Choi WS, Kim HI, Kwak SS, Chung HY, Chung HY, Yamamoto K, et al. Amorphous ultrafine particle preparation for improvement of bioavailability of insoluble drugs: grinding characteristics of fine grinding mills. Int J Miner Process 2004;74:165-72.
7. Choi JY, Yoo JY, Kwak HS, Nam BU, Lee J. Role of polymeric stabilizers for drug nano crystal dispersions. Curr Appl Phys 2005;5:472-4.
8. Paradkar A, Ambike AA, Jadhav BK, Mahadik K. Characterization of curcuminâ€“PVP solid dispersion obtained by spray drying. Int J Pharm 2004;271:281-6.
9. Gao L, Zhang D, Chen M, Zheng T, Wang S. Preparation and characterization of an oridonin nanosuspension for solubility and dissolution velocity enhancement. Drug Dev Ind Pharm 2007;33:1332-9.
10. Chen Y, Zhang G, Neilly J, Marsh K, Mawhinney D, Sanzgiri Y. Enhancing the bioavailability of ABT-963 using solid dispersion containing Pluronic F-68. Int J Pharm 2004;286:69-80.
11. Jun SW, Kim MS, Kim JS, Park HJ, Lee S, Woo JS, et al. Preparation and characterization of simvastatin/hydroxypropyl-Î²-cyclodextrin inclusion complex using supercritical antisolvent (SAS) process. Eur J Pharm Biopharm 2007;66:413-21.
12. Sweetman SC. Martindale: the complete drug reference. 34th ed. Pharmaceutical Press. London and Chicago; 2005. p. 900-1.
13. Paul Y, Kumar M, Singh B. Formulation and in vitro evaluation of Gastroretentive drug delivery system of cefixime trihydrate. Int J Drug Dev Res 2011;3:148-61.
14. Arora S, Sharma P, Irchhaiya R, Khatkar A, Singh N, Gagoria J. Development, characterization and solubility study of solid dispersion of cefpodoxime proxetil by solvent evaporation method. Int J ChemTech Res 2010;2:1156-62.
15. Khan FA, Zahoor M, Islam NU, Hameed R. Synthesis of cefixime and azithromycin nanoparticles: an attempt to enhance their antimicrobial activity and dissolution rate. J Nanomater 2016. http://dx.doi.org/10.1155/2016/6909085
16. Choi SH, Lee JS. Inventors; international health management associates, Inc., assignee. Complexes to improve oral absorption of poorly absorbable antibiotics. United States patent US; 2001. p. 360.
17. Wenzel U, Kuntz S, Diestel S, Daniel H. PEPT1-mediated cefixime uptake into human intestinal epithelial cells is increased by Ca2+channel blockers. Antimicrob Agents Chemother 2002;46:1375-80.
18. Loftsson T, Muellertz A, Siepmann J. For the special IJP issue Poorly soluble drugsâ€. Int J Pharm 2013;1:1-2.
19. Bevernage J, Brouwers J, Brewster ME, Augustijns P. Evaluation of gastrointestinal drug supersaturation and precipitation: strategies and issues. Int J Pharm 2013;453:25-35.
20. MÃ¼ller RH, Peters K. Nanosuspensions for the formulation of poorly soluble drugs: I. Preparation by a size-reduction technique. Int J Pharm 1998;160:229-37.
21. MÃ¶schwitzer JP. Drug nanocrystals in the commercial pharmaceutical development process. Int J Pharm 2013;453:142-56.
22. MÃ¼ller RH, Gohla S, Keck CM. State of the art of nanocrystalsâ€“special features, production, nanotoxicology aspects and intracellular delivery. Eur J Pharm Biopharm 2011;78:1-9.
23. Keck CM, MÃ¼ller RH. Drug nanocrystals of poorly soluble drugs produced by high-pressure homogenization. Eur J Pharm Biopharm 2006;62:3-16.
24. Van Eerdenbrugh B, Van den Mooter G, Augustijns P. Top-down production of drug nanocrystals: nanosuspension stabilization, miniaturization and transformation into solid products. Int J Pharm 2008;364:64-75.
25. Wang Y, Zheng Y, Zhang L, Wang Q, Zhang D. Stability of nano suspensions in drug delivery. J Controlled Release 2013;172:1126-41.
26. Deng Z, Xu S, Li S. Understanding a relaxation behaviour in a nanoparticle suspension for drug delivery applications. Int J Pharm 2008;351:236-43.
27. Wu L, Zhang J, Watanabe W. Physical and chemical stability of drug nanoparticles. Adv Drug Delivery Rev 2011;63:456-69.
28. Verma S, Huey BD, Burgess DJ. Scanning probe microscopy method for nanosuspension stabilizer selection. Langmuir 2009;25:12481-7.
29. Gassmann P, List M, Schweitzer A, Sucker H. Hydrosols: alternatives for the parenteral application of poorly water-soluble drugs. Eur J Pharm Biopharm 1994;40:64-72.
30. Abdelwahed W, Degobert G, Stainmesse S, Fessi H. Freeze-drying of nanoparticles: formulation, process and storage considerations. Adv Drug Delivery Rev 2006;58:1688-713.
31. Chaubal MV, Popescu C. Conversion of nanosuspensions into dry powders by spray drying: a case study. Pharm Res 2008;25:2302-8.
32. Gao Y, Zuo J, Bou-Chacra N, Pinto TD, Clas SD, Walker RB, et al. In vitro release kinetics of anti-tuberculosis drugs from nanoparticles assessed using a modified dissolution apparatus. BioMed Res Int 2013. http://dx.doi.org/10.1155/2013/ 136590.
33. Gupta S, Chavhan S, Sawant KK. Self-nano emulsifying drug delivery system for adefovir dipivoxil: design, characterization, in vitro and ex vivo evaluation. Colloids Surf A 2011;392:145-55.
34. Quan P, Shi K, Piao H, Piao H, Liang N, Xia D, et al. A novel surface modified nitrendipine nanocrystals with enhancement of bioavailability and stability. Int J Pharm 2012;430:366-71.
35. Gao L, Zhang D, Chen M. Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system. J Nanopart Res 2008;10:845-62.
36. Benvegnu T, Plusquellec D, LemiÃ¨gre L. Surfactants from renewable sources: synthesis and applications. Monomers Polym Compos Renewable Resour 2008;3:153-78.
37. Tolman JA, Williams III RO. Advances in the pulmonary delivery of poorly water-soluble drugs: influence of solubilization on pharmacokinetic properties. Drug Dev Ind Pharm 2010;3:1-30.
38. Somasundaram I, Kumar SS. Pramipexole dihydrochloride loaded mpeg-pcl nanosuspension by modified nano-precipitation: in vitro and in vivo evaluation. Asian J Pharm Clin Res 2016;6:161-7.