AAPS PharmSciTech

, Volume 19, Issue 7, pp 3228–3236 | Cite as

Preparation of a Mesoporous Structure of SnO2 for Increasing the Oral Bioavailability and Dissolution Rate of Nitrendipine

  • Xuan Liu
  • Chao WuEmail author
  • Andi Bai
  • Huiling Lv
  • Xiaoyan Xu
  • Yue Cao
  • Wenjing Shang
  • Lili Hu
  • Ying Liu
Research Article


In this study, mesoporous SnO2 (MSn) with a three-dimensional mesoporous structure was prepared using MCM-48 as the template in order to increase the oral bioavailability and dissolution rate of insoluble drugs. The model drug, nitrendipine (NDP), was loaded into the MSn by the adsorption method. The structural features of MSn were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and N2 adsorption (desorption) analysis. NDP was existed in the pore channels of MSn in an amorphous state, which was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). MSn showed a good biocompatibility in the cell toxicity assay for Caco-2 cells. In vitro dissolution results suggested that MSn could significantly enhance the dissolution rate of NDP compared with commercial NDP tablets. Pharmacokinetic studies indicated that NDP-MSn tablets effectively enhanced the oral bioavailability of NDP. In conclusion, MSn was found to be a potential carrier for improving the solubility of insoluble drugs.


mesoporous material tin oxide insoluble drugs oral bioavailability dissolution rate 



This study was supported by the National Natural Science Foundation of China (no. 81302707), the Natural Science Foundation of Liaoning Province (no. 20170540366), Liaoning province talent project support programs in colleges and universities (no. LJQ2015065), and the Principal Fund-Aohong-boze-clinical medicine construction Special Fund (no. XZJJ20140205).


  1. 1.
    Alsante KM, Ando A, Brown R, Ensing J, Hatajik TD, Kong W, et al. The role of degradant profiling in active pharmaceutical ingredients and drug products. Adv Drug Deliver Rev. 2007;59(1):29–37.CrossRefGoogle Scholar
  2. 2.
    Blagden N, de Matas M, Gavan PT, York P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Deliver Rev. 2007;59(7):617–30.CrossRefGoogle Scholar
  3. 3.
    Prachi BS, Varsha BP. Understanding peroral absorption: regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles. Acta Pharm Sin B. 2017;7(3):260–80.CrossRefGoogle Scholar
  4. 4.
    Tiwari G, Tiwari R, Rai AK. Cyclodextrins in delivery systems: applications. J Pharm Bio Sci. 2010;2(2):72–9.CrossRefGoogle Scholar
  5. 5.
    Yohei K, Koichi W, Manabu N, Shizuo Y, Satomi O. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications. Int J Pharm. 2011;420(1):1–10.CrossRefGoogle Scholar
  6. 6.
    Jiahui H, Johnston KP, Williams RO III. Spray freezing into liquid (SFL) particle engineering technology to enhance dissolution of poorly water soluble drugs: organic solvent versus organic/aqueous co-solvent systems. Eur J Pharm Sci. 2003;20(3):295–303.CrossRefGoogle Scholar
  7. 7.
    Maheshwari RK. Mixed-solvency approach-boon for solubilization of poorly water-soluble drugs. ASIA. J Pharm Sci. 2014;4(1):60–3.Google Scholar
  8. 8.
    Greenwald RB, Gilbert CW, Pendri A, Conover CD, Xia J, Martinez A. Drug delivery systems: water soluble Taxol 2 ‘-poly (ethylene glycol) Ester prodrugs design and in vivo effectiveness. J Med Chem. 1996;39(2):424–31.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Anil KP, Jolanta FKL, James RJB. Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex. Adv Drug Deliver Rev. 2005;57(15):2203–14.CrossRefGoogle Scholar
  10. 10.
    Lukyanov AN, Torchilin VP. Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs. Adv Drug Deliver Rev. 2004;56(9):1273–89.CrossRefGoogle Scholar
  11. 11.
    Lei G, Dianrui Z, Minghui C. Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system. J Nanopart Res. 2008;10(5):845–62.CrossRefGoogle Scholar
  12. 12.
    Kawakami K, Yoshikawa T, Moroto Y, Kanaoka E, Takahashi K, Nishihara Y, et al. Microemulsion formulation for enhanced absorption of poorly soluble drugs: I. Prescription design. J Control Release. 2002;81(1–2):65–74.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Serajuddin A. Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J Pharm Sci-US. 1999;88(10):1058–66.CrossRefGoogle Scholar
  14. 14.
    Nikhil B. Modified mesoporous silica nanoparticles for enhancing oral bioavailability and antihypertensive activity of poorly water soluble valsartan. Eur J Pharm Sci. 2017;99:152–60.CrossRefGoogle Scholar
  15. 15.
    Aziz M, Helene K, Aurélie S, Jessica MR, Valeria A, Mehrdad H. Mesoporous silica materials: from physico-chemical properties to enhanced dissolution of poorly water-soluble drugs. J Control Release. 2017;268(28):329–47.Google Scholar
  16. 16.
    Yanzhuo Z, Zhuangzhi Z, Tongying J, Jinghai Z, Wang Z, Siling W. Spherical mesoporous silica nanoparticles for loading and release of the poorly water-soluble drug telmisartan. J Control Release. 2010;145(3):257–63.CrossRefGoogle Scholar
  17. 17.
    Aitana T, Alejandra M, Roberto RC, Araceli MI, Luis MB, Dolores VO, et al. Mesoporous silicon oxycarbide materials for controlled drug delivery systems. Chem EngJ. 2015;280:165–74.CrossRefGoogle Scholar
  18. 18.
    Xiufang W, Ping L, Yong T, Linquan Z. Novel synthesis of Fe-containing mesoporous carbons and their release of ibuprofen. Micropor Mesopor Mat. 2011;145(1–3):98–103.Google Scholar
  19. 19.
    Patricia H, Christian S, María VR, Muriel S, Francis T, Gérard F. Metal-organic frameworks as efficient materials for drug delivery. Angew Chem. 2006;118(36):6120–4.CrossRefGoogle Scholar
  20. 20.
    Ranjit T, Amit D, William J, Maya PL, Lilly R, Naír RH. Pharmaceutical cocrystals and poorly soluble drugs. Int J Pharm. 2013;453:101–25.CrossRefGoogle Scholar
  21. 21.
    Mehdi Y, Sana F, Soroush B, Iman G, Hassan F, Hamidreza M. Facile synthesis of chitosan/ZnO bio-nanocomposite hydrogel beads as drug delivery systems. Int J Biol Macromol. 2016;82:273–8.CrossRefGoogle Scholar
  22. 22.
    Zhila ZA, Hassan F, Behrouz FN, Saeedeh A, Mehdi Y, Mohammad KG. PH-sensitive bionanocomposite hydrogel beads based on carboxymethyl cellulose/ZnO nanoparticle as drug carrier. Int J Biol Macromol. 2016;93:1317–27.CrossRefGoogle Scholar
  23. 23.
    Javed R, Ahmed M, Haq I, Nisa S, Zia M. PVP and PEG doped CuO nanoparticles are more biologically active: antibacterial, antioxidant, antidiabetic and cytotoxic perspective. Mat Sci Eng C-Mater. 2017;79(1):108–15.CrossRefGoogle Scholar
  24. 24.
    Farzaneh S, Ida IM. Acrylamide-based hydrogel drug delivery systems: release of acyclovir from MgO nanocomposite hydrogel. J Taiwan Inst Chem E 2017;72:182–193.CrossRefGoogle Scholar
  25. 25.
    Ana MD, Angel LD. Antibacterial SnO2 nanorods as efficient fillers of poly (propylene fumarate-co-ethylene glycol) biomaterials. Mat Sci Eng C-Mater. 2017;78:806–16.CrossRefGoogle Scholar
  26. 26.
    Na C, Miao L, Yanbao Z, Li Q, Xueyan Z, Yu Z, et al. Fabrication of SnO2/porous silica/polyethyleneimine nanoparticles for pH-responsive drug delivery. Mat Sci Eng C-Mater. 2016;59:319–23.CrossRefGoogle Scholar
  27. 27.
    Jibin G, Nana Z, Yinglei Z, Chunxia C, Hongming C, Tianhong Z. Pharmacokinetic performance of the nitrendipine intravenous submicron emulsion in rats. Asian J Pharm Sci. 2014;9:330–5.CrossRefGoogle Scholar
  28. 28.
    Kaneda M, Tsubakiyama T, Carlsson A, Sakamoto Y, Ohsuna T, Terasaki O. Structural study of mesoporous MCM-48 and carbon networks synthesized in the spaces of MCM-48 by electron crystallography. J Phys Chem B. 2002;106(6):1256–66.CrossRefGoogle Scholar
  29. 29.
    Jie X, Zhaohua L, Heyong H, Wuzong Z, Larry K. A reliable synthesis of cubic mesoporous MCM-48 molecular sieve. Chem Mater. 1998;10:3690–8.CrossRefGoogle Scholar
  30. 30.
    Swasmi P, Hongwei Z, Xiaodan H, Hao S, Yannan Y, Jun Z, et al. Mesoporous magnesium oxide hollow spheres as superior arsenite adsorbent: synthesis and adsorption behavior. ACS Appl Mater Inter. 2016;8:25306–12.CrossRefGoogle Scholar
  31. 31.
    Pierrick G, Sophie D, Habiba N, Joël P, Jean FB, Emmanuel F, et al. Synthesis of CuO/SBA-15 adsorbents for sox removal applications, using different impregnation methods. C R Chim. 2015;18:1013–29.CrossRefGoogle Scholar
  32. 32.
    Peng Q, Dengning X, Hongze P, Hongyu P, Kai S, Yinnong J, et al. Nitrendipine nanocrystals: its preparation, characterization, and in vitro-in vivo evaluation. AAPS PharmSciTech. 2011;12(4):1136–43.CrossRefGoogle Scholar
  33. 33.
    Priya VS, Sadhana JR. A comparative in vitro release study of raloxifene encapsulated ordered MCM-41 and MCM-48 nanoparticles: a dissolution kinetics study in simulated and biorelevant media. J Drug Deliv Sci Tec. 2017;41:31–44.CrossRefGoogle Scholar
  34. 34.
    Ying Z, Chao W, Zongzhe Z, Yanna H, Jie X, Tong Y, et al. Preparation of starch macrocellular foam for increasing the dissolution rate of poorly water-soluble drugs. Pharm Dev Technol. 2016;21(6):749–54.Google Scholar
  35. 35.
    Peng Q, Kai S, Hongze P, Hongyu P, Na L, Dengning X, et al. A novel surface modified nitrendipine nanocrystals with enhancement of bioavailability and stability. Int J Pharm. 2012;430:366–71.CrossRefGoogle Scholar
  36. 36.
    Ghasemi S, Farsangi ZJ, Beitollahi A, Mirkazemi M, Rezayat SM, Sarkar S. Synthesis of hollow mesoporous silica (HMS) nanoparticles as a candidate for sulfasalazine drug loading. Ceram Int. 2017;43:11225–32. CrossRefGoogle Scholar
  37. 37.
    Hongjian G, Yating Z, Jia L, Yu C, Ying W, Qinfu Z, et al. Hollow mesoporous silica as a high drug loading carrier for regulation insoluble drug release. Int J Pharm. 2016;510:184–94.CrossRefGoogle Scholar
  38. 38.
    Basu SK, Adhiyaman R. Preparation and characterization of nitrendipine-loaded Eudragit RL 100 microspheres prepared by an emulsion-solvent evaporation method. Trop J Pharm Res. 2008;7(3):1033–41.CrossRefGoogle Scholar
  39. 39.
    Yangong Z, Jing W, Pengjun Y. Formaldehyde sensing properties of electrospun NiO-doped SnO2 nanofibers. Sesors Actuat B-Chem. 2011;156(2):723–30.CrossRefGoogle Scholar
  40. 40.
    Jing L, Na F, Chang L, Jian W, Sanming L, Zhonggui H. The tracking of interfacial interaction of amorphous solid dispersions formed by water-soluble polymer and nitrendipine. Appl Surf Sci. 2017;420:136–44.CrossRefGoogle Scholar
  41. 41.
    Yanna H, Chao W, Zongzhe Z, Ying Z, Jie X, Yang Q, et al. Development of a novel starch with a three-dimensional ordered macroporous structure for improving the dissolution rate of felodipine. Mat Sci Eng C-Mater. 2016;58:1131–7.CrossRefGoogle Scholar
  42. 42.
    Tianshi F, Huayu T, Caina X, Lin L, Zhigang X, Michael HL, et al. Synergistic co-delivery of doxorubicin andpaclitaxelby porous PLGA microspheres for pulmonary inhalation treatment. Eur J Pharm Biophar. 2014;88:1086–93.CrossRefGoogle Scholar
  43. 43.
    Hai W, Ying Z, Yan W, Yulin H, Kaihui N, Guangjun N, et al. Enhanced anti-tumor efficacy by co-delivery of doxorubicin and paclitaxel with amphiphilic methoxy PEG-PLGA copolymer nanoparticles. Biomaterials. 2011;32:8281–90.CrossRefGoogle Scholar
  44. 44.
    Kesisoglou F, Panmai S, Yunhui W. Nanosizing-oral formulation development and biopharmaceutical evaluation. Adv Drug Deliv Rev. 2007;59:631–44.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Dengning X, Peng Q, Hongze P, Hongyu P, Shaoping S, Yongmei Y, et al. Preparation of stable nitrendipine nanosuspensions using the precipitation-ultrasonication method for enhancement of dissolution and oral bioavailability. Eur J Pharm Sci. 2010;40:325–34.CrossRefGoogle Scholar
  46. 46.
    Cogswell S, Berger S, Waterhouse D, Bally MB, Wasan EK. A parenteral econazole formulation using a novel micelle-to-liposome transfer method: in vitro characterization and tumor growth delay in a breast cancer xenograft model. Pharm Res. 2006;23:2575–85.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Shchekin AK, Rusanov AI. Generalization of the Gibbs-Kelvin-Köhler and Ostwald-Freundlich equations for a liquid film on a soluble nanoparticle. J Chem Phys. 2008;129:154116.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Xuan Liu
    • 1
  • Chao Wu
    • 1
    Email author
  • Andi Bai
    • 1
  • Huiling Lv
    • 1
  • Xiaoyan Xu
    • 1
  • Yue Cao
    • 1
  • Wenjing Shang
    • 1
  • Lili Hu
    • 1
  • Ying Liu
    • 1
  1. 1.Pharmacy SchoolJinzhou Medical UniversityJinzhouChina

Personalised recommendations