Synthesis of hollow vaterite CaCO(3) microspheres in supercritical carbon dioxide medium

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Synthesis of hollow vaterite CaCO

₃

microspheres in supercritical carbon dioxide medium

Thomas Beuvier,

^a

Brice Calvignac,

^b

Ga€ etan Jean-Robert Delcroix,

^b

My Kien Tran,

^b

St ephanie Kodjikian,

^c

Nicolas Delorme,

^a

Jean-Franc¸ois Bardeau,

^a

Alain Gibaud

^a

and Frank Boury*

^b

Received 21st February 2011, Accepted 4th May 2011 DOI: 10.1039/c1jm10770d

We here describe a rapid method for synthesizing hollow core, porous crystalline calcium carbonate microspheres composed of vaterite using supercritical carbon dioxide in aqueous media, without surfactants. We show that the reaction in alkaline media rapidly conducts to the formation of microspheres with an average diameter of 5mm. SEM, TEM and AFM observations reveal that the microspheres have a hollow core of around 0.7mm width and are composed of nanograins with an average diameter of 40 nm. These nanograins are responsible for the high specific surface area of 16 m² g¹deduced from nitrogen absorption/desorption isotherms, which moreover confers an important porosity to the microspheres. We believe this work may pave the way for the elaboration of a biomaterial with a large potential for therapeutic as well as diagnostic applications.

Introduction

Hollow calcium carbonate particles have attracted considerable attention owing to their excellent properties such as low density, high specific surface areas and drugs, inks or pigments micro- encapsulation. Colloidosomes were for example extensively studied to generate hollow structure.^1,2 Organic templates or matrices can notably mimic the biomineralized architectures and control growth, morphology and polymorph of calcium carbonate crystals. In this way, hollow CaCO₃microspheres of calcite were successively formed in mild conditions by reaction of Na2CO3with CaCl2 in the presence of polyacrylic acid (PAA) and sodium dodecyl sulfonate (SDS),³ sodium dodecyl sulfate and a Pluronic F127 copolymer⁴ or double-hydrophilic block copolymer–surfactant mixtures.⁵ Magnesium chloride was also sometimes added to promote the growth of aragonite CaCO₃ polymorph.⁶ Vaterite, the least thermodynamically stable variety, can also be kinetically stabilized by different biomole- cules such as poly(glutamic) acid,⁷ glycine,^8,9 L-alanine⁹ or aspartic acid.^10,11

Precipitation of vaterite-type calcium carbonate particles is typically obtained either by mixing calcium salt and carbonate solution,^12,13or by passing carbon dioxide (CO2) gas into calcium salt solution (emulsion template method or ‘‘bubble template’’

method).^14,15In the bubble template precipitation method, the kinetics of the aqueous solution carbonation is relatively slow due to the low CO2dissolution. Recently Hou and Feng reported the precipitation of vaterite by diffusion of NH4HCO3vapor into CaCl2 solutions for 24 h.⁸ To accelerate the efficiency of carbonation, supercritical CO₂ (Sc-CO₂) can be used (critical pressure: 73.8 bar, critical temperature: 31.1 C) as already described for the production of precipitated calcium carbonate.^16,17 Sc-CO2 is an attractive solvent because of its tunable physical properties with small variations in pressure and temperature. Sc-CO₂ also has excellent transport properties (with gas-like viscosity and diffusivity) and solvent power (with liquid-like density).^18,19 Hence, Sc-CO₂ reveals to be a unique synthesis and processing medium.²⁰In addition, it is a naturally, non-toxic, non-flammable and environmentally benign solvent.²¹ The solubility of Sc-CO2in water is around 30 times higher than at ambient temperature and pressure.²²According to Hanet al.,²³ the higher is the concentration of CO₃², the higher will be the tendency for the formation of vaterite rather than its dissolution and subsequent transformation into calcite. Thus, Sc-CO2seems to be favorable for the formation and the stability of the meta- stable vaterite phase.

However, only few research groups have made use of Sc-CO₂ for the preparation of CaCO3 particles. Formation of calcium carbonate particles by direct contact of Ca(OH)2powders with Sc-CO2has been reported by Guet al.¹⁶and leads to non-porous rhombohedral calcite particles. In aqueous media, preparation of CaCO₃/polyacrylamide composites has also been reported using

aLunam Universite du Maine, Laboratoire de Physique de l’Etat Condens e UMR CNRS 6087, Universite du Maine, 72085 Le Mans, France. E-mail:

thomas.beuvier@univ-lemans.fr; nicolas.delorme@univ-lemans.fr;

jean-francois.bardeau@univ-lemans.fr; alain.gibaud@univ-lemans.fr

bLunam Universite du Maine, INSERM U646 ‘Ingenierie de la Vectorisation Particulaire’ IBS-CHU ANGERS, batiment IRIS, 4 rue^ Larrey, 49933 Angers Cedex 9, France. E-mail: frank.boury@

univ-angers.fr; brice.calvignac@univ-angers.fr; delcroix.gaetan@gmail.

com; mykiend2002@yahoo.com; Fax: +33 (0)2.44.68.85.46; Tel: +33 (0)2.44.68.85.28

cLunam Universite du Maine, Laboratoire Des Oxydes et Fluorures UMR CNRS 6010, Universite du Maine, 72085 Le Mans, France. E-mail:

stephanie.kodjikian@univ-lemans.fr

Materials Chemistry

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supercritical carbon dioxide at 60C and 28 bar.²⁴In this study, formed particles are either inhomogeneous with spherical and rhombohedral shapes, or porous spheres with large diameters of around 50mm depending on the content of FC4430, a commer- cial surfactant. No information on the polymorph was given.

Finally Wakayamaet al.²⁵reported films formation of vaterite CaCO3particles of around 12mm width on glass or organic slides at 50C and 75 bar. Thus, vaterite particles can be obtained in Sc-CO₂ media but no details were provided about their morphology and porosity.

In the present paper, calcium carbonate microparticles were prepared by using a rapid water/Sc-CO2 emulsion technique without any surfactant or solid substrate. XRD, SEM, AFM, TEM and nitrogen adsorption/desorption analyses were performed to precisely characterize the crystallinity, the morphology including the porosity of the calcium carbonate microspheres formed during this process.

Results and discussion

Structural analysis by XRD

Fig. 1 shows the X-ray diffraction pattern of our CaCO₃ microspheres. The peaks observed are characteristic of the vaterite polymorph of CaCO3. The presence of the peak at 29.3 is attributed to the most intense peak of calcite and according to the works of Dickinson and McGrath,²⁶ we estimate that the molar content of calcite is about 2%. According to the Debye–

Scherrer equation, coherence lengths derived from XRD line width analysis were approximately 305 nm. Thus, depending on the peak considered, the size of a vaterite crystal that composed the microspheres varied between 25 and 35 nm in diameter.

Surface morphology by SEM and AFM

SEM observations indicate that the CaCO₃microspheres were around 5 mm in diameter, with a relatively narrow size distribution (mean diameter ¼4.91.0mm) (inset of Fig. 2(a)). A detail of an isolated microsphere (Fig. 2(b)) is depicted in Fig. 2 (c). Its surface is composed of agglomerated vaterite nanograins.

Similar micrographs of the surface of vaterite particles prepared by mixing calcium salt and carbonate solution^13,27or by bubbling method²³are observed in the literature. An analysis of the top of a microsphere obtained by AFM shows that the nanograins are around 40 nm width (Fig. 2(d)), which is close to the vaterite crystal size determined by XRD. According to Hanet al.,²³the nano-sized vaterite crystals seem to be stabilized by their important agglomeration, which firstly reduces the solubility of fine particles and secondly limits the transformation into calcite.

Internal morphology by TEM and SEM

To go further in the understanding of the crystallization phenomena, we investigated the inner structure of the microspheres. Fig. 3(a) represents TEM observations of a microsphere.

Fig. 1 Representative X-ray diffractogram of the vaterite CaCO3

microspheres. Bragg reflexions of vaterite (ICSD 15879) are indicated with vertical markers below the profile. *Calcite.

Fig. 2 (a) SEM image of CaCO3microspheres synthesized in Sc-CO2. The inset shows the particle diameter distribution. (b) SEM image of an isolated particle and (c) a zoom of its surface showing external rugosity/

porosity. (d) AFM topography image on the centre of another particle.

The grey bar refers to the height of the sample from 0 nm (in black) to 80 nm (in white).

Fig. 3 Inner structure of the CaCO3microspheres. (a) TEM image of a particle with its diameter brightness profile suggesting the presence of a hollow core. (b) SEM image of the broken particle.

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In opposition to a homogeneous sphere model, we observed that the brightness of the core is higher than the one of the shell. The brightness profile is plotted below the TEM image. This obser- vation suggests that the centre of the particle is less dense than its surface.

To confirm this assumption, powder was slightly grinded in a mortar and dispersed on a carbon scotch. A broken particle is shown in Fig. 3(b). SEM analysis shows that the interior of a microsphere is not homogeneous. Holes are present and their concentration seems to gradually increase from the surface to the centre, with even a hollow core of 0.7mm width. Noteworthy, the ratio of the hollow core diameter on wall thickness is around 0.3.

Moreover, we observe radial fibrous units of around 1mm length.

Hence, it is supposed that growth of the CaCO₃microparticles is radial, as already observed by Weiet al.who used a soft chemical process.²⁸

Porosity by nitrogen adsorption

To investigate the porosity of the CaCO3 microspheres, N2

adsorption–desorption at 77 K was carried out. The isotherms are reported in Fig. 5. The gas adsorption in theP/P₀¼0.1–0.3 range gives a specific surface area of 16 m²g¹calculated by the BET equation (Fig. 4, inset), similar to the one reported by Yu et al.²⁹on smaller (1–2mm) particles. This value is high compared to the 5mm particle diameter and may be explained by the high specific surface area of nanograins agglomerated on the surface and by the accessible internal porosity. The adsorption and desorption isotherms show a pronounced hysteresis at P/P0>

0.43 due to the N2capillary condensation which takes place into mesopores. This hysteresis loop belongs to the type H₃according to the IUPAC classification (i.e.with no limiting absorption at highP/P₀). It is characteristic of an assemblage of particles which are loosely coherent.³⁰Thus, the nanograins which compose the microspheres may be not strongly joined together and are probably responsible for this typical H3hysteresis loop. More- over, atP/P₀¼0.43, the desorption curve exhibits a strong drop in the N₂adsorbed volume. This sudden transformation of liquid nitrogen to gaseous nitrogen is often referred to as the Tensile Strength Effect (TSE). According to Groen et al.,³¹ this

phenomenon may become even more pronounced when pore networks are present and when interconnected larger pores have to empty through pores with a smaller diameter, which connect larger pores to the outer surface of the particles. Thus, we can suggest that microspheres of vaterite exhibit macropores and mesopores inside the particles, which are connected from the outer surface only by smaller pores located in the more compact shell. This assumption is supported by the previous observations where a packing of nanograins was gradually lower from the shell to the core.

Experimental

Carbonation reaction media

The synthesis method used in this study was patented by Boury et al.³²and developed in our laboratory. The method is based on the formation of an emulsion of water in Sc-CO2(W/C) for which microdroplets act as microreactors where several reactions succeed.

Here, Sc-CO2acts as a continuous (or external) phase and as reactant for the synthesis of CaCO3particles. The fast diffusion of CO2 molecules into a basic aqueous solution leads to the formation of ionic species such as HCO₃and CO₃²(eq (1)–(3)).

Then, the CO₃² ions react with Ca²⁺ ions to form calcium carbonate (eq (4)) which may crystallize under different polymorphs.

CO2+ H2O4H2CO34HCO3+ H⁺ (1)

CO2+ HO4HCO3 (2)

HCO₃+ HO4CO₃²+ H₂O (3) CO₃²+ Ca²⁺4CaCO₃ (4)

Preparation of aqueous solution

This solution contains 0.62 M NaCl (VWR international, Fontenay-sous-bois, France) and 0.62 M glycine (Sigma-Aldrich, Saint-Quentin-Fallavier, France) buffer at pH 10. Then, calcium hydroxide Ca(OH)₂(Sigma-Aldrich) is added (0.8% w/v) before adjustment of the pH to 10 and filtration (0.45 mm). Lastly, hyaluronic acid obtained from Streptococcus equi. (Sigma- Aldrich, Mw: 1630 kDa) is added (0.1% w/v) to behave as a template molecule directing the polymorphism of CaCO₃ particles.

Experimental setup and procedure

A schematic diagram of the device used for CaCO₃synthesis is shown in Fig. 5. The stainless autoclave (1) with a capacity of 500 mL (Separex, Champigneulles, France) is heated at 40.0 0.1C and pressurized with CO2at 2001 bar. Liquid CO2is pumped by a high pressure membrane pump (Milton Roy Europe, Pont Saint Pierre, France) (2) and preheated by a heat exchanger (Separex, Champigneulles, France) (3) before feeding the autoclave equipped with a stirring mechanical device (Top- industrie, Vaux le Penil, France). The axis of the magnetic stirrer Fig. 4 Nitrogen adsorption–desorption isotherms of the CaCO3

microspheres. The inset refers to the BET specific surface area analysis.

Open and filled circles refer to adsorption and desorption isotherms.

TSE: tensile strength effect.

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is equipped with an anchor stirrer and the stirring speed is 1200 rpm. Once, the equilibrium is reached (temperature and pressure constant), 25 mL of aqueous solution previously prepared are injected by means of an HPLC pump (Model 307, Gilson, Villiers le bel, France) (4). Injection flow is fixed to 10 mL min¹. Once addition is achieved, the final pressure is 2405 bar and stirring is maintained at 1200 rpm for 5 min. Thereafter, stirring is stopped and the autoclave depressurized at a rate of 40–50 bar min¹.

Suspension of CaCO₃ microparticles is collected and centrifuged at 2400gfor 10 min. Lastly, microparticles are washed with 50 mL of ultrapure water (Millipore, Molsheim, France), centrifuged and lyophilised (Model Lyovax GT2, Steris, Mentor, USA) to obtain a dry powder of CaCO₃.

Characterization techniques

Microsphere size measurements were performed with both dynamic light scattering (Beckman Coulter LS13320, Brea, CA, USA) and SEM measurement techniques. However, preparation of the samples for DLS led to a small degradation of the samples so that only results obtained with microscopic observations are presented in the Results section. X-Ray diffraction (XRD) patterns were collected in reflection mode on powder spread out on a glass substrate. The measurement was performed with an X-pert diffractometer using Cu-Karadiation (l ¼ 1.54056A) from 2q¼10 to 70in continuous mode with a step size of 0.07. Scanning electron microscopy images (SEM; JEOL 6310F, Croissy sur Seine, France) were obtained with a tungsten cathode field emission gun operating at 3 kV on powder dispersed on a carbon scotch substrate. Atomic force microscopy measurements were performed with an Agilent 5500 AFM. All the topography images were realized in intermittent contact mode using the same PPP-NCHR-W tip (Nanosensors, Neuchatel, Switzerland). Image processing and grain size analysis were performed with the Gwyddion freeware. Transmission electron microscopy (TEM) studies were carried out (JEOL 2010, Croissy sur Seine, France) with a LaB₆ thermo-ionic emission source operating at 200 kV. The sample was dispersed in absolute ethanol and one droplet was deposited on a carbon-coated holey

film supported by a copper grid before drying. The isothermal adsorption/desorption curves were recorded with an ASAP 2010 (Micrometrics, Norcross, GA, USA) system by using nitrogen gas. Prior to the determination of the isotherms, the physisorbed species are removed from the surface of the absorbent by exposing the sample to a high vacuum (5mm Hg) at 100C for 8 h.

Conclusion

In the present work, we described a method for synthesizing spherical calcium carbonate particles with an average diameter of 5mm using Sc-CO2in aqueous media. Due to the fast dissolution of CO₂in aqueous solution, the reaction rapidly conducts to the formation of calcium carbonate microspheres crystallized in vaterite polymorph, the least thermodynamically stable CaCO3

variety. AFM observations reveal that microparticles were composed of nanograins of 40 nm diameter which are less and less packed from the shell to the hollow core. This core is around 0.7mm width as shown by SEM and TEM analysis. N₂adsorption–desorption isotherms show a specific surface area of 16 m² g¹and an important tensile strength effect, which reflects that large pores inside the particles are connected from the outer surface by smaller pores located in the more compact shell. It is noteworthy that several parameters can influence the formation of such hollow particles. Recently we started to investigate the effects of various formulation parameters belonging either to the nature of the solution (concentration of calcium precursor, volume and pH of the solution, nature and concentration of the template molecule,.) or the process conditions (pressure, temperature, agitation, time of reaction,.) using an experimental design. These studies should help us to better understand which parameters are critical to tune the structure and the morphology of the microspheres. Nonetheless, the present work shows promising results for the elaboration of a biocompatible material composed of inorganic and/or organic compounds, which may have (i) therapeutic applications with encapsulation of bioactive molecules and (ii) diagnostic applications with the incorporation of contrast agents.

Acknowledgements

The authors thank the financial support of ANR (France—

Project ANR-09-PIRI-0004-01), Regional research program (Pays de Loire, France—Bioregos program) and CNRS (France). The authors thank the Institut des Materiaux Jean Rouxel (Nantes, France) for nitrogen adsorption/desorption measurements and the SCIAM laboratory (Angers, France) for SEM analysis.

References

1 Y. Pan, J. Gao, B. Zhang, X. Zhang and B. Xu,Langmuir, 2011,26, 4184–4187.

2 S. Hyuk Im, U. Jeong and Y. Xia,Nat. Mater., 2005,4, 671–675.

3 Y. Pan, X. Zhao, Y. Guo, X. Lv, S. Ren, M. Yuan and Z. Wang, Mater. Lett., 2007,61, 2810–2813.

4 G. W. Yan, J. H. Huang, J. F. Zhang and C. J. Qian,Mater. Res.

Bull., 2008,43, 2069–2077.

5 L. Qi, J. Li and J. Ma,Adv. Mater., 2002,14, 300–303.

6 D. Walsh and S. Mann,Nature, 1995,377, 320–323.

7 T. Kato, T. Sakamoto and T. Nishimura,MRS Bull., 2010,35, 127.

8 W. Hou and Q. Feng,J. Cryst. Growth, 2005,282, 214–219.

Fig. 5 Scheme of the experimental setup.

(5)

9 C. Shivkumara, P. Singh, A. Gupta and M. S. Hegde,Mater. Res.

Bull., 2006,41, 1455–1460.

10 H. Tong, W. Ma, L. Wang, P. Wan, J. Hu and L. Cao,Biomaterials, 2004,25, 3923–3929.

11 T. Kato, T. Suzuki, T. Amamiya, T. Irie, M. Komiyama and H. Yui, Supramol. Sci., 1998,5, 411–415.

12 C. G. Kontoyannis and N. V. Vagenas,Analyst, 2000,125, 251–255.

13 M. Kitamura,J. Colloid Interface Sci., 2001,236, 318–327.

14 Y. S. Han, G. Hadiko, M. Fuji and M. Takahashi,J. Cryst. Growth, 2005,276, 541–548.

15 H. Watanabe, Y. Mizuno, T. Endo, X. Wang, M. Fuji and M. Takahashi,Adv. Powder Technol., 2009,20, 89–93.

16 W. Gu, D. W. Bousfield and C. P. Tripp,J. Mater. Chem., 2006,16, 3312–3317.

17 C. Domingo, J. Garcıa-Carmona, E. Loste, A. Fanovich, J. Fraile and J. Gomez-Morales, J. Cryst. Growth, 2004,271, 268–273.

18 A. Fenghour and W. A. Wakeham,J. Phys. Chem., 1998,27, 31–44.

19 R. Span and W. Wagner, J. Phys. Chem. Ref. Data, 1996, 25, 1509.

20 J. A. Darr and M. Poliakoff,Chem. Rev., 1999,99, 495–542.

21 A. I. Cooper,J. Mater. Chem., 2000,10, 207–234.

22 G. Ferrentino, D. Barletta, M. O. Balaban, G. Ferrari and M. Poletto, J. Supercrit. Fluids, 2010,52, 142–150.

23 Y. Han, G. Hadiko, M. Fuji and M. Takahashi,J. Mater. Sci., 2006, 41, 4663–4667.

24 Z. Bing, J. Y. Lee, S. W. Choi and J. H. Kim,Eur. Polym. J., 2007,43, 4814–4820.

25 H. Wakayama, S. R. Hall and S. Mann,J. Mater. Chem., 2005,15, 1134–1136.

26 S. R. Dickinson and K. M. McGrath,Analyst, 2001,126, 1118–1121.

27 C. Peng, Q. Zhao and C. Gao,Colloids Surf., A, 2010,353, 132–139.

28 W. Wei, G. H. Ma, G. Hu, D. Yu, T. McLeish, Z. G. Su and Z. Y. Shen,J. Am. Chem. Soc., 2008,130, 15808–15810.

29 J. Yu, H. Guo, S. A. Davis and S. Mann,Adv. Funct. Mater., 2006,16, 2035–2041.

30 K. S. W. Sing, D. H. Everett, R. A. W. Haul, L. Moscou, R. A. Pierotti, J. Rouquerol and T. Siemeniewska, Pure Appl.

Chem., 1985,57, 603–619.

31 J. C. Groen, L. A. A. Peffer and J. Perez-Ramırez, Microporous Mesoporous Mater., 2003,60, 1–17.

32 F. Boury, J. P. Benoit, O. Thomas and F. Tewes,Method for preparing particles from an emulsion in supercritical or liquid CO2, 2007.