Dissolution and storage stability of nanostructured calcium carbonates and phosphates for nutrition

  • Lidija Posavec
  • Jesper T. N. KnijnenburgEmail author
  • Florentine M. Hilty
  • Frank Krumeich
  • Sotiris E. Pratsinis
  • Michael B. Zimmermann
Research Paper


Rapid calcium (Ca) dissolution from nanostructured Ca phosphate and carbonate (CaCO3) powders may allow them to be absorbed in much higher fraction in humans. Nanosized Ca phosphate and CaCO3 made by flame-assisted spray pyrolysis were characterized by nitrogen adsorption, X-ray diffraction (XRD), Raman spectroscopy, and transmission electron microscopy. As-prepared nanopowders contained both CaCO3 and CaO, but storing them under ambient conditions over 130 days resulted in a complete transformation into CaCO3, with an increase in both crystal and particle sizes. The small particle size could be stabilized against such aging by cation (Mg, Zn, Sr) and anion (P) doping, with P and Mg being most effective. Calcium phosphate nanopowders made at Ca:P ≤ 1.5 were XRD amorphous and contained γ-Ca2P2O7 with increasing hydroxyapatite content at higher Ca:P. Aging of powders with Ca:P = 1.0 and 1.5 for over 500 days gradually increased particle size (but less than for CaCO3) without a change in phase composition or crystallinity. In 0.01 M H3PO4 calcium phosphate nanopowders dissolved ≈4 times more Ca than micronsized compounds and about twice more Ca than CaCO3 nanopowders, confirming that nanosizing and/or amorphous structuring sharply increases Ca powder dissolution. Because higher Ca solubility in vitro generally leads to greater absorption in vivo, these novel FASP-made Ca nanostructured compounds may prove useful for nutrition applications, including supplementation and/or food fortification.


Flame-assisted spray pyrolysis (FASP) Calcium carbonate Calcium phosphate Doping Aging Dissolution Food 



The authors would like to thank Seline Staub for her assistance with production and analysis of the carbonate-containing powders. Also, the authors would like to thank Burgerstein Vitamins, Switzerland, for donating Ca compounds used in these studies. TEM measurements were taken at ScopeM (ETH Zurich). This work was financially supported by ETH Research Grant ETH-06 10-1 and the Swiss South African Joint Research Programme (project number IZLSZ3_149090).

Supplementary material

11051_2016_3608_MOESM1_ESM.pdf (587 kb)
Supplementary material 1 (PDF 587 kb)


  1. Ali M, Winterer M (2010) ZnO nanocrystals: surprisingly ‘alive’. Chem Mater 22:85–91CrossRefGoogle Scholar
  2. Brennan MJ, Duncan WE, Wartofsky L, Butler VM, Wray HL (1991) In vitro dissolution of calcium carbonate preparations. Calcif Tissue Int 49:308–312CrossRefGoogle Scholar
  3. Camenzind A, Strobel R, Pratsinis SE (2005) Cubic or monoclinic Y2O3: Eu3+ nanoparticles by one step flame spray pyrolysis. Chem Phys Lett 415:193–197CrossRefGoogle Scholar
  4. Cheary RW, Coelho A (1992) A fundamental parameters approach to X-ray line profile fitting. J Appl Crystallogr 25:109–121CrossRefGoogle Scholar
  5. Chen SF, Yu SH, Jiang J, Li FQ, Liu YK (2006) Polymorph discrimination of CaCO3 mineral in an ethanol/water solution: formation of complex vaterite superstructures and aragonite rods. Chem Mater 18:115–122CrossRefGoogle Scholar
  6. Chen HS, Chang JH, Wu JSB (2008) Calcium bioavailability of nanonized pearl powder for adults. J Food Sci 73:H246–H251CrossRefGoogle Scholar
  7. Chou L, Garrels RM, Wollast R (1989) Comparative study of the kinetics and mechanisms of dissolution of carbonate minerals. Chem Geol 78:269–282CrossRefGoogle Scholar
  8. European Commission (1998) Report on osteoporosis in the European Community: action for prevention. Office for official publications for the European Commission, LuxembourgGoogle Scholar
  9. Davis KJ, Dove PM, de Yoreo JJ (2000) The role of Mg2+ as an impurity in calcite growth. Science 290:1134–1137CrossRefGoogle Scholar
  10. de Leeuw NH (2002) Molecular dynamics simulations of the growth inhibiting effect of Fe2+, Mg2+, Cd2+, and Sr2+ on calcite crystal growth. J Phys Chem B 106:5241–5249CrossRefGoogle Scholar
  11. Dheilly RM, Tudo J, Queneudec M (1998) Influence of climatic conditions on the carbonation of quicklime. J Mater Eng Perform 7:789–795CrossRefGoogle Scholar
  12. Dickmann RS, Strasburg GM, Romsos DR, Wilson LA, Lai GH, Huang H (2016) Particle size, surface area, and amorphous content as predictors of solubility and bioavailability for five commercial sources of ferric orthophosphate in ready-to-eat cereal. Nutrients 8:14 ppGoogle Scholar
  13. Doman RC, Barr JB, McNally RN, Alper AM (1963) Phase equilibria in the system CaO-MgO. J Am Ceram Soc 46:313–316CrossRefGoogle Scholar
  14. Dorozhkin SV (2007) Calcium orthophosphates. J Mater Sci 42:1061–1095CrossRefGoogle Scholar
  15. Economou ED, Evmiridis NP, Vlessidis AG (1996) Dissolution kinetics of CaCO3 in powder form and influence of particle size and pretreatment on the course of dissolution. Ind Eng Chem Res 35:465–474CrossRefGoogle Scholar
  16. Frear GL, Deese EF, Lefforge JW (1944) Calcium metaphosphate—effect of impurities on fusibility, citrate solubility, and hygroscopicity. Ind Eng Chem 36:835–840CrossRefGoogle Scholar
  17. Goldsmith JR, Heard HC (1961) Subsolidus phase relations in the system CaCO3-MgCO3. J Geol 69:45–74CrossRefGoogle Scholar
  18. Gomez-Villalba LS, Lopez-Arce P, Alvarez de Buergo M, Fort R (2011) Structural stability of a colloidal solution of Ca(OH)2 nanocrystals exposed to high relative humidity conditions. Appl Phys A-Mater Sci Process 104:1249–1254CrossRefGoogle Scholar
  19. Gueguen L, Pointillart A (2000) The bioavailability of dietary calcium. J Am Coll Nutr 19:119S–136SCrossRefGoogle Scholar
  20. Hansen C, Werner E, Erbes HJ, Larrat V, Kaltwasser JP (1996) Intestinal calcium absorption from different calcium preparations: influence of anion and solubility. Osteoporos Int 6:386–393CrossRefGoogle Scholar
  21. Hausner DB, Reeder RJ, Strongin DR (2007) Humidity-induced restructuring of the calcite surface and the effect of divalent heavy metals. J Colloid Interface Sci 305:101–110CrossRefGoogle Scholar
  22. Haynes WM (2015–2016) CRC Handbook of Chemistry and PhysicsGoogle Scholar
  23. Heaney RP, Recker RR, Weaver CM (1990) Absorbability of calcium sources—the limited role of solubility. Calcif Tissue Int 46:300–304CrossRefGoogle Scholar
  24. Heaney RP, Dowell MS, Barger-Lux MJ (1999) Absorption of calcium as the carbonate and citrate salts, with some observations on method. Osteoporos Int 9:19–23CrossRefGoogle Scholar
  25. Hilty FM, Teleki A, Krumeich F, Buchel R, Hurrell RF, Pratsinis SE, Zimmermann MB (2009) Development and optimization of iron- and zinc-containing nanostructured powders for nutritional applications. Nanotechnol 20:475101CrossRefGoogle Scholar
  26. Hilty FM, Arnold M, Hilbe M, Teleki A, Knijnenburg JTN, Ehrensperger F, Hurrell RF, Pratsinis SE, Langhans W, Zimmermann MB (2010) Iron from nanocompounds containing iron and zinc is highly bioavailable in rats without tissue accumulation. Nat Nanotechnol 5:374–380CrossRefGoogle Scholar
  27. Hilty FM, Knijnenburg JTN, Teleki A, Krumeich F, Hurrell RF, Pratsinis SE, Zimmermann MB (2011) Incorporation of Mg and Ca into nanostructured Fe2O3 improves Fe solubility in dilute acid and sensory characteristics in foods. J Food Sci 76:N2–N10CrossRefGoogle Scholar
  28. Huang S, Chen JC, Hsu CW, Chang WH (2009) Effects of nano calcium carbonate and nano calcium citrate on toxicity in ICR mice and on bone mineral density in an ovariectomized mice model. Nanotechnol 20:375102CrossRefGoogle Scholar
  29. Huber M, Stark WJ, Loher S, Maciejewski M, Krumeich F, Baiker A (2005) Flame synthesis of calcium carbonate nanoparticles. Chem Commun. doi: 10.1039/B411725E
  30. Imel EA, DiMeglio LA, Burr DB (2014) Chapter 16—Metabolic bone diseases. In: Burr DB, Allen MR (eds) Basic and applied bone biology. Academic Press, San Diego, pp 317–344CrossRefGoogle Scholar
  31. Institute of Medicine (1997) Dietary reference intake for calcium, phosphorus, magnesium, vitamin D and fluoride. National Academy Press, WashingtonGoogle Scholar
  32. Jossen R, Pratsinis SE, Stark WJ, Madler L (2005) Criteria for flame-spray synthesis of hollow, shell-like, or inhomogeneous oxides. J Am Ceram Soc 88:1388–1393CrossRefGoogle Scholar
  33. Knijnenburg JTN, Hilty FM, Krumeich F, Zimmermann MB, Pratsinis SE (2013) Multimineral nutritional supplements in a nano-CaO matrix. J Mater Res 28:1129–1138CrossRefGoogle Scholar
  34. Knijnenburg JTN, Seristatidou E, Hilty FM, Krumeich F, Deligiannakis Y (2014) Proton-promoted iron dissolution from nanoparticles and the influence by the local iron environment. J Phys Chem C 118:24072–24080CrossRefGoogle Scholar
  35. Loher S, Stark WJ, Maciejewski M, Baiker A, Pratsinis SE, Reichardt D, Maspero F, Krumeich F, Gunther D (2005) Fluoro-apatite and calcium phosphate nanoparticles by flame synthesis. Chem Mater 17:36–42CrossRefGoogle Scholar
  36. Loste E, Wilson RM, Seshadri R, Meldrum FC (2003) The role of magnesium in stabilising amorphous calcium carbonate and controlling calcite morphologies. J Cryst Growth 254:206–218CrossRefGoogle Scholar
  37. Lu H, Smirniotis PG, Ernst FO, Pratsinis SE (2009) Nanostructured Ca-based sorbents with high CO2 uptake efficiency. Chem Eng Sci 64:1936–1943CrossRefGoogle Scholar
  38. Madler L, Kammler HK, Mueller R, Pratsinis SE (2002) Controlled synthesis of nanostructured particles by flame spray pyrolysis. J Aerosol Sci 33:369–389CrossRefGoogle Scholar
  39. Mao ZQ, Maeno Y, Fukazawa H (2000) Crystal growth of Sr2RuO4. Mater Res Bull 35:1813–1824CrossRefGoogle Scholar
  40. Margolis HC, Moreno EC (1992) Kinetics of hydroxyapatite dissolution in acetic, lactic, and phosphoric acid solutions. Calcif Tissue Int 50:137–143CrossRefGoogle Scholar
  41. Marie PJ, Ammann P, Boivin G, Rey C (2001) Mechanisms of action and therapeutic potential of strontium in bone. Calcif Tissue Int 69:121–129CrossRefGoogle Scholar
  42. Meiron OE, Bar-David E, Aflalo ED, Shechter A, Stepensky D, Berman A, Sagi A (2011) Solubility and bioavailability of stabilized amorphous calcium carbonate. J Bone Miner Res 26:364–372CrossRefGoogle Scholar
  43. Meyer K (1998) Characterisation of the structure of binary calcium ultraphosphate glasses by infrared and Raman spectroscopy. Phys Chem Glasses 39:108–117Google Scholar
  44. Morse JW, Arvidson RS, Luttge A (2007) Calcium carbonate formation and dissolution. Chem Rev 107:342–381CrossRefGoogle Scholar
  45. Mueller R, Madler L, Pratsinis SE (2003) Nanoparticle synthesis at high production rates by flame spray pyrolysis. Chem Eng Sci 58:1969–1976CrossRefGoogle Scholar
  46. Nordin BEC (1997) Calcium and osteoporosis. Nutrition 13:664–686CrossRefGoogle Scholar
  47. Orchard TS, Larson JC, Alghothani N, Bout-Tabaku S, Cauley JA, Chen Z, LaCroix AZ, Wactawski-Wende J, Jackson RD (2014) Magnesium intake, bone mineral density, and fractures: results from the Women’s Health Initiative Observational Study. Am J Clin Nutr 99:926–933CrossRefGoogle Scholar
  48. Pak CYC, Avioli LV (1988) Factors affecting absorbability of calcium from calcium salts and food. Calcif Tissue Int 43:55–60CrossRefGoogle Scholar
  49. Pak CYC, Poindexter J, Finlayson B (1989) A model system for assessing physicochemical factors affecting calcium absorbability from the intestinal tract. J Bone Miner Res 4:119–127CrossRefGoogle Scholar
  50. Pemberton JE, Latifzadeh L, Fletcher JP, Risbud SH (1991) Raman spectroscopy of calcium phosphate glasses with varying CaO modifier concentrations. Chem Mater 3:195–200CrossRefGoogle Scholar
  51. Puech J, Heughebaert JC, Montel G (1982) A new mode of growing apatite crystallites. J Cryst Growth 56:20–24CrossRefGoogle Scholar
  52. Recker RR (1985) Calcium absorption and achlorhydria. N Engl J Med 313:70–73CrossRefGoogle Scholar
  53. Rohner F, Ernst FO, Arnold M, Hilbe M, Biebinger R, Ehrensperger F, Pratsinis SE, Langhans W, Hurrell RF, Zimmermann MB (2007) Synthesis, characterization, and bioavailability in rats of ferric phosphate nanoparticles. J Nutr 137:614–619Google Scholar
  54. Rudin T, Pratsinis SE (2012) Homogeneous iron phosphate nanoparticles by combustion of sprays. Ind Eng Chem Res 51:7891–7900CrossRefGoogle Scholar
  55. Rudin T, Wegner K, Pratsinis SE (2011) Uniform nanoparticles by flame-assisted spray pyrolysis (FASP) of low cost precursors. J Nanopart Res 13:2715–2725CrossRefGoogle Scholar
  56. Shih SM, Ho CS, Song YS, Lin JP (1999) Kinetics of the reaction of Ca(OH)2 with CO2 at low temperature. Ind Eng Chem Res 38:1316–1322CrossRefGoogle Scholar
  57. Silaban A, Harrison DP (1995) High temperature capture of carbon dioxide: Characteristics of the reversible reaction between CaO(s) and CO2(g). Chem Eng Commun 137:177–190CrossRefGoogle Scholar
  58. Sipponen P, Harkonen M (2010) Hypochlorhydric stomach: a risk condition for calcium malabsorption and osteoporosis? Scand J Gastroenterol 45:133–138CrossRefGoogle Scholar
  59. Strobel R, Pratsinis SE (2007) Flame aerosol synthesis of smart nanostructured materials. J Mater Chem 17:4743–4756CrossRefGoogle Scholar
  60. Stumm W, Morgan JJ (1996) Aquatic chemistry: chemical equilibria and rates in natural waters. Wiley, New YorkGoogle Scholar
  61. Sun LM, Chow LC, Frukhtbeyn SA, Bonevich JE (2010) Preparation and properties of nanoparticles of calcium phosphates with various Ca/P ratios. J Res Natl Inst Stand Technol 115:243–255CrossRefGoogle Scholar
  62. Tsugawa N, Yamabe T, Takeuchi A, Kamao M, Nakagawa K, Nishijima K, Okano T (1999) Intestinal absorption of calcium from calcium ascorbate in rats. J Bone Miner Metab 17:30–36CrossRefGoogle Scholar
  63. Vaisman N, Shaltiel G, Daniely M, Meiron OE, Shechter A, Abrams SA, Niv E, Shapira Y, Sagi A (2014) Increased calcium absorption from synthetic stable amorphous calcium carbonate: double-blind randomized crossover clinical trial in postmenopausal women. J Bone Miner Res 29:2203–2209CrossRefGoogle Scholar
  64. Weaver CM, Gallant KMH (2014) Chapter 14—Nutrition. In: Burr DB, Allen MR (eds) Basic and applied bone biology. Academic Press, San Diego, pp 283–297CrossRefGoogle Scholar
  65. Willis RB, Allen PR (1999) Measurement of amorphous ferric phosphate to assess iron bioavailability in diets and diet ingredients. Analyst 124:425–430CrossRefGoogle Scholar
  66. Wopenka B, Pasteris JD (2005) A mineralogical perspective on the apatite in bone. Mater Sci Eng C 25:131–143CrossRefGoogle Scholar
  67. Yang LC, Kim P, Meyer HM, Agnihotri S (2009) Aging of nanocarbons in ambient conditions: Probable metastability of carbon nanotubes. J Colloid Interface Sci 338:128–134CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Lidija Posavec
    • 1
  • Jesper T. N. Knijnenburg
    • 1
    Email author
  • Florentine M. Hilty
    • 1
  • Frank Krumeich
    • 2
  • Sotiris E. Pratsinis
    • 2
  • Michael B. Zimmermann
    • 1
  1. 1.Human Nutrition Laboratory, Institute of Food, Nutrition and Health, Department of Health Sciences and TechnologyETH ZurichZurichSwitzerland
  2. 2.Particle Technology Laboratory, Institute of Process Engineering, Department of Mechanical and Process EngineeringETH ZurichZurichSwitzerland

Personalised recommendations