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Development of Duloxetine Hydrochloride Loaded Mesoporous Silica Nanoparticles: Characterizations and In Vitro Evaluation

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Abstract

This study investigated the potential use of mesoporous silica nanoparticles (MSNs) as a carrier for duloxetine hydrochloride (DX), which is prone to acid degradation. Sol–gel and solvothermal methods were used to synthesize the MSNs, which, after calcination and drug loading, were then characterized using X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) technique, thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and diffuse reflectance ultraviolet-visible (DRS-UV-Vis) spectroscopy. Releases of DX from the MSNs were good in pH 7.4 (90%) phosphate buffer but poor in acidic pH (40%). In a comparative release study between the MSNs in phosphate buffer, TW60-3DX showed sustained release for 140 h, which was higher than the other nanoparticles. The mechanism of DX release from the MSNs was studied using Peppas kinetics model. The “n” value of all three MSNs ranged from 0.45 to 1 with a correlation coefficient (r 2) >0.9, which indicated that the release of the drug from the system follows the anomalous transport or non-Fickian diffusion. The results supported the efficacy of mesoporous silica nanoparticles synthesized here as a promising carrier for duloxetine hydrochloride with higher drug loading and greater pH-sensitive release.

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References

  1. Vallet-Regi M, Ra’mila A, del Real RP, Pe’rez-Pariente JA. New property of MCM-41: drug delivery system. Chem Mater. 2001;13:308–11.

    Article  CAS  Google Scholar 

  2. Salonen J, Kaukonen AM, Hirvonen J, Lehto VP. Mesoporous silicon in drug delivery applications. J Pharm Sci. 2008;97:632–53.

    Article  CAS  PubMed  Google Scholar 

  3. Colilla M, González B, Vallet-Regí M. Mesoporous silica nanoparticles for the design of smart delivery nanodevices. Biomater Sci. 2013;1:114–34.

    Article  CAS  Google Scholar 

  4. Tang F, Li L, Chen D. Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater. 2012;24:1504–34.

    Article  CAS  PubMed  Google Scholar 

  5. Hirvonen J, Laaksonen T, Peltonen L, Santos H, Lehto V-P, Heikkilä T, et al. Feasibility of silicon-based mesoporous materials for oral drug delivery applications. Dosis. 2008;24:129–49.

    Google Scholar 

  6. Horcajada P, Ramila A, Perez-Pariente J, Vallet-Regi M. Influence of poresize of MCM-41 matrices on drug delivery rate. Micro Meso Mater. 2004;68:105–9.

    Article  CAS  Google Scholar 

  7. Friedrich H, Fussnegger B, Kolter K, Bodmeier R. Dissolution rate improvement of poorly water-soluble drugs obtained by adsorbing solutions of drugs inhydrophilic solvents onto high surface area carriers. Eur J Pharm Biopharm. 2006;62:171–7.

    Article  CAS  PubMed  Google Scholar 

  8. Chen C-Y, Li H-X, Davis ME. Studies on mesoporous materials. I. Synthesis and characterization of MCM-41. Micro Meso Mater. 1993;2:17–26.

    Article  Google Scholar 

  9. Tanev PT, Pinnavaia TJ. A neutral templating route to mesoporous molecular sieves. Science. 1995;267:865–7.

    Article  CAS  PubMed  Google Scholar 

  10. Shahbazi M-A, Herranz B, Santos HA. Nanostructured porous Si-based nanoparticles for targeted drug delivery. Biomatter. 2012;2:296–312.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Ukmar T, Planinek O. Ordered mesoporous silicates as matrices for controlled release of drugs. Acta Pharm. 2010;60:373–85.

    Article  CAS  PubMed  Google Scholar 

  12. Mehrdad M. Synthesis and characterization of pH-sensitive silica nanoparticles for oral-insulin delivery. Current Drug Deliv. 2011;8:607–11.

    Article  Google Scholar 

  13. Kumar D, SailajaChirravuri SV, Shastri NR. Impact of surface area of silica particles on dissolution rate and oralbioavailability of poorly water soluble drugs: a case study with aceclofenac. Int J Pharm. 2014;461:459–68.

    Article  CAS  PubMed  Google Scholar 

  14. Charnay C, Begu, Tourn-Pateilh C, Nicole L, Lerner DA, Devoisselle JM. Inclusion of ibuprofen in mesoporous templated silica: drug loading and release property. Eur J Pharm Biopharm. 2004;57:533–40.

    Article  CAS  PubMed  Google Scholar 

  15. Ambrogi V, Perioli L, Marmottini F, Accorsi O, Pagano C, Ricci M, et al. Role of mesoporous silicates on carbamazepine dissolution rate enhancement. Micro Meso Mater. 2008;113:445–52.

    Article  CAS  Google Scholar 

  16. Zhu Y, Shi J, Shen W, Dong X, Feng J, Ruan M, et al. Uniform magnetic hollow spheres with a magnetic core/mesoporous silica shell structure. Angew Chem Int Ed Engl. 2005;4:5083–7.

    Article  Google Scholar 

  17. Mal N, Fujiwara M, Tanaka Y. Photocontrolled reversible release of guest molecules from coumarin-modified mesoporous silica. Nature. 2003;421:350–3.

    Article  CAS  PubMed  Google Scholar 

  18. He Q, Gao Y, Zhang L, Zhang Z, Gao F, Ji X, et al. A pH-responsive mesoporous silica nanoparticles-based multi-drug delivery system for overcoming multi-drug resistance. Biomaterials. 2011;32:7711–20.

    Article  CAS  PubMed  Google Scholar 

  19. Van SM, Mellaerts R, Thi TD, Martens JA, Van Humbeeck J, Annaert P, et al. Preventing release in the acidic environment of the stomach via occlusion in ordered mesoporous silica enhances the absorption of poorly soluble weakly acidic drugs. J Pharm Sci. 2011;100:4864–76.

    Article  Google Scholar 

  20. Ganesh M, Hemalatha P, Mei Mei P, Palanichamy M, Ubaidulla U, Jang HT. Synthesis and characterization of pharmaceutical surfactant templated mesoporous silica: its application to controlled delivery of duloxetine. Mater Res Bull. 2014;51:228–35.

    Article  Google Scholar 

  21. Roggers R, Kanvinde S, Boonsith S, Oupick D. The practicality of mesoporous silica nanoparticles as drug delivery devices and progress toward this goal. AAPS PharmSciTech. 2014;15:1163–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Ganesh M, Lee SG. Synthesis, characterization and drug release capability of new cost effective mesoporous silica nano particles for ibuprofen drug delivery. Int J Cont Auto. 2013;6:207–16.

    Article  Google Scholar 

  23. Salonen J, Laitinen L, Kaukonen AM, Tuura J, Bjorkqvist M, Heikkila T, et al. Mesoporous silicon microparticles for oral drug delivery: loading and release of five model drugs. J Contol Release. 2005;108:362–74.

    Article  CAS  Google Scholar 

  24. Popovici RF, Seftel EM, Mihai GD, Popovici E, Voicu AV. Controlled drug delivery system based on ordered mesoporous silica matrices of captopril as angiotensin-converting enzyme inhibitor drug. J Pharm Sci. 2011;100:704–14.

    Article  CAS  PubMed  Google Scholar 

  25. Ng JBS, Kamali-Zare P, Brismar H, Bergstrom L. Release and molecular transport of cationic and anionic fluorescent molecules in mesoporous silica spheres. Langmuir. 2008;24:11096–102.

    Article  CAS  PubMed  Google Scholar 

  26. Vinita V, Nagesh U, Mittapalli N, Kumar P, DR. Reddy’s Laboratories, assignee. Pharmaceutical formulations comprising duloxetine, United States patent, 20090226517A1, 2009

  27. Zhao R-K, Cheng G, Tang J, Song J, Peng W-X. Pharmacokinetics of duloxetine hydrochloride enteric-coated tablets in healthy Chinese volunteers: a randomized, open-label, single- and multiple-dose study. Clin Ther. 2009;31:1022–36.

    Article  CAS  PubMed  Google Scholar 

  28. Gopferich A, Tessmar J. Polyanhydride degradation and erosion. Adv Drug Deliv Rev. 2002;54:911–31.

    Article  CAS  PubMed  Google Scholar 

  29. Patel K, Padhye S, Nagarsenker M. Duloxetine HCl lipid nanoparticles: preparation, characterization, and dosage form design. AAPS PharmSciTech. 2012;13:125–33.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Ganesh M, Hemalatha P, Mei Mei P, Rajasekar K, Jang HT. A new fluoride mediated synthesis of mesoporous silica and their usefulness in controlled delivery of duloxetine hydrochloride a serotonin re-uptake inhibitor. J Ind Eng Chem. 2012;18:684–9.

    Article  CAS  Google Scholar 

  31. Yunoos M, Sankar DG, Kumar BP, Hameed S, Hussain A. Simple UV spectrophotometric determination of duloxetine hydrochloride in bulk and in pharmaceutical formulations. E-J Chem. 2010;7:785–8.

    Article  CAS  Google Scholar 

  32. Ritger PL, Peppas NA. A simple equation for description of solute release. I. Fickian and non-Fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J Control Release. 1987;5:23–36.

    Article  CAS  Google Scholar 

  33. Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv. 1985;60:110–1.

    CAS  PubMed  Google Scholar 

  34. Marjo CE, Bhadbhade M, Hook JM, Rich AM. Polymorphism and a metastable Solvate of duloxetine hydrochloride. Mol Pharm. 2011;8:2454–64.

    Article  CAS  PubMed  Google Scholar 

  35. Newa M, Bhandari KH, Oh DH, Kim YR, Sung JH, Kim JO, et al. Enhanced dissolution of ibuprofen using solid dispersion with poloxamer. 407. Arch Pharm Res. 2008;31:1497–507.

    Article  CAS  PubMed  Google Scholar 

  36. Labudzinska A, Gorczynska K. The UV difference spectra as a characteristic feature of phenols and aromatic amines. J Mol Str. 1995;349:469–72.

    Article  CAS  Google Scholar 

  37. Sugimoto Y, Nishimura S, Imoto E. The ultraviolet spectra of the thiophene derivatives. Opera 1959;71–81

  38. Landau MV, Varkey SP, Herskowitz M, Regev O, Pevzner S, Sen T, et al. Wetting stability of Si-MCM-41 mesoporous material in neutral, acidic and basic aqueous solutions. Micro Meso Mater. 1999;33:149–63.

    Article  CAS  Google Scholar 

  39. Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci. 1961;50:874–5.

    Article  CAS  PubMed  Google Scholar 

  40. Kuang Y, Zhao L, Zhang S, Zhang F, Dong M, Xu S. Morphologies, preparations and applications of layered double hydroxide micro-/nanostructures. Materials. 2010;3:5220–35.

    Article  CAS  Google Scholar 

  41. Wei M, Pu M, Guo J, Han J, Li F, He J, et al. Intercalation of l-dopa into layered double hydroxides: enhancement of both chemical and stereochemical stabilities of a drug through host-guest interactions. Chem Mater. 2008;20:5169–80.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was financially supported by grants from the Korea CCS R&D Center, funded by the Ministry of Education, Science and Technology of the Korean Government. The authors extend their thanks to National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (Grant No. 2014-004694) for their partial financial support.

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Authors and Affiliations

  1. Department of Chemical Engineering, Hanseo University, Seosan-si, 356 706, South Korea

    Mani Ganesh, Pushparaj Hemalatha, Mei Mei Peng & Hyun Tae Jang

  2. Department of Pharmaceutics, C.L.Baid Metha College of Pharmacy, Chennai, India

    Udhumansha Ubaidulla

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  1. Mani Ganesh
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  2. Udhumansha Ubaidulla
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  3. Pushparaj Hemalatha
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  4. Mei Mei Peng
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  5. Hyun Tae Jang
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Correspondence to Hyun Tae Jang.

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Ganesh, M., Ubaidulla, U., Hemalatha, P. et al. Development of Duloxetine Hydrochloride Loaded Mesoporous Silica Nanoparticles: Characterizations and In Vitro Evaluation. AAPS PharmSciTech 16, 944–951 (2015). https://doi.org/10.1208/s12249-014-0273-x

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