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Preparation and characterization of hollow hydroxyapatite microspheres by spray drying method
Materials Science and Engineering C 29 (2009) 1088–1092
Contents lists available at ScienceDirect
Materials Science and Engineering C j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / m s e c
Short communication
Preparation and characterization of hollow hydroxyapatite microspheres by spray drying method Ruixue Sun a, Yupeng Lu b,⁎, Kezheng Chen a a b
College of Materials Science and Engineering, Qingdao University of Science and Technology, Qingdao 266042, China School of Materials Science and Engineering, Shandong University, Jinan 250061, China
a r t i c l e
i n f o
Article history: Received 5 November 2007 Received in revised form 30 July 2008 Accepted 7 August 2008 Available online 22 August 2008 Keywords: Hydroxyapatite Hollow microspheres Spray drying Characterization
a b s t r a c t Hollow hydroxyapatite (Ca10(PO4)6(OH)2) microspheres were prepared using a simple spray drying method. The incorporation of ammonium bicarbonate could produce carbon dioxide and ammonia gas bubbles during the spraying, and thus created a hollow inner structure in the resultant microspheres. The hollow microspheres prepared using different amounts of ammonium bicarbonate were also characterized. These microspheres were composed of nanoparticles with an average crystallite size of 15 nm. A high surface area (80 m2/g) and porosity of the microspheres could be achieved when the concentration of ammonium bicarbonate was about 5 wt.%. Fourier transform infrared results showed that CO2− 3 was incorporated into the HA microspheres. These hollow microspheres have many potential uses such as injectable drug-delivery carriers. © 2008 Published by Elsevier B.V.
1. Introduction Hydroxyapatite (HA) is widely used in areas of orthopaedic and dental surgery, separation and purification because of its unique properties related to good biocompatibility, osteoconduction and excellent adsorption properties [1]. There are many reports about HA coatings and HA composite bioceramic materials [2–4]. However, there are few reports about HA microspheres, especially hollow HA microspheres [5,6]. HA microspheres have many unusual properties such as large specific surface area, good flowability and so on. HA microspheres have received much attention owing to its special structure, changeable properties and wide range of applications. Recently, several methods have been developed to prepare HA microspheres with dimensions ranging from submicron to micron size for use in sustained-release drug-delivery systems [6–9]. The spray drying method is particularly attractive because of its widespread use and relative ease of operation. P. Luo et al. prepared HA powders with controlled morphology including doughnut shapes, solid spheres or hollow spheres by using this spray drying method [10,11]; Y. Mizushima et al. fabricated spherical porous HA microparticles as an injectable drug carrier by the spray drying method [1]. And the in vivo experiment results suggest the possibility of the HA microspheres used as an excellent drug carrier for sustained-release. Compared with the simple spherical HA particles, the HA microspheres with porous and hollow structure have more excellent
⁎ Corresponding author. Tel./fax: +86 531 88395966. E-mail address: [email protected] (Y. Lu). 0928-4931/$ – see front matter © 2008 Published by Elsevier B.V. doi:10.1016/j.msec.2008.08.010
properties such as low density and large encapsulation capacity. However, there have been few reports of the hollow HA microspheres prepared by spray drying method, which incorporate an adequate amount of drugs and can release them slowly [12,13]. In this study, we fabricated hollow HA microspheres by the spray drying method and ammonium bicarbonate was used as a gas foaming agent, which can generate carbon dioxide and ammonia gas bubbles during the spraying. The resultant hollow microspheres prepared with different amounts of ammonium bicarbonate were also characterized. 2. Materials and methods 2.1. Preparation of the HA microspheres The feedstock HA precipitates were prepared by using a wet method according to the following reaction: 10Ca(NO 3 ) 2 + 6 (NH4)2HPO4 +8NH4OH→Ca10(PO4)6(OH)2 +20NH4NO3 +6H2O. Briefly, aqueous solutions of Ca(NO3)2·4H2O and (NH4)2HPO4 with Ca/P ratio of 1.67 were prepared, respectively. The pH of the two solutions was adjusted to 10–11 by using NH4OH. Under vigorous stirring, the (NH4)2HPO4 solution was added to the Ca(NO3)2·4H2O solution and the resultant HA precipitate was aged at room temperature. Then the precipitates were washed with distilled water several times to remove nitrate ions and ammonium ions. After removing the supernatant from the aged precipitates, distilled water was added to dilute the precipitates to some extent. Ammonium bicarbonate (NH4HCO3) was dissolved in distilled water at different concentrations ranging from 1– 7 wt.% and was added to the HA slurry under magnetic stirring. Then they were spray dried using a GPW120-II small-type spray dryer. In
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Fig. 1. SEM micrographs of hollow HA microspheres with 3 wt.% NH4HCO3.
brief, the mixture was atomized at a pressure of 15 L/min and a flow rate of 400 ml/h, while the inlet and outlet temperatures of the nozzle were adjusted to 170 °C and 100 °C, respectively. The product was dried at 180 °C for 1 d, or calcined at 500 °C and 800 °C for 1 h, respectively. 2.2. Characterization The morphology of the spray dried HA microspheres was examined by scanning electron microscope (SEM) (a Hitachi S-570, Japan) and field emission SEM (a JEOL JSM6700F microscope, Japan). The phase analysis was carried out using a Japan Rigaku D/max-γB X-
ray diffractometer (XRD), with a scan speed of 4°/min between 10 and 60 °2θ angle, operated at 40 kV and 100 mA. A Nicolet Nexus-470 Fourier transform infrared (FTIR) spectroscope was used to characterize the functional groups of the microspheres. The particle size distribution and mean particle size were measured using a LS13320 Laser Diffraction Particle Size Analyzer (Beckman-Coulter, America) and distilled water was employed as the dispersion medium. The diameter measurement error of this equipment is equal to about 3%. The specific surface area and pore size distribution were determined by the Brunauer–Emmett–Teller (BET) method using a Coulter SA3100 Surface Area Analyzer after being degassed at 200 °C for 2 h and
Fig. 2. FE-SEM micrographs of HA microspheres.
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Fig. 3. Schematic illustration of the formation of hollow microspheres.
using nitrogen as the absorbent. The surface area measurement error of this equipment is equal to about 3%. 3. Results and discussion 3.1. Microstructure of the hollow HA microspheres Fig. 1 shows the SEM micrographs of hollow HA microspheres prepared by spray drying. It can be seen from Fig. 1a that the spray dried microparticles are spherical and there are “black” points on the surface of almost all microspheres. At higher magnification (Fig. 1a, b and c), we can see that the “black” points are open pores on the surface of the microspheres and the pore diameter ranges from approximately 0.2–1.5 µm. The hollow structure of the microspheres can be clearly observed from Fig. 1c and d. The hollow region appeared as regular sphere located at the center of a porous microsphere shell. In addition, Fig. 1 shows that most of the microparticles kept their spherical morphology after spray drying, which indicates that the hollow microspheres have sufficient strength for further handling and processing. The FE-SEM micrographs of HA microspheres are shown in Fig. 2. It can be seen that the shell of the hollow HA microsphere is composed of homogeneous HA crystallites. In fact, spray dried HA microspheres have already been reported by some researchers [1,10], but there have been no reports about hollow HA microsphere fabricated using NH4HCO3 as a gas foaming agent. In the present study, different amounts of NH4HCO3 were added into the HA slurry before spray drying to optimize hollow HA microparticle formation. Under continuous stirring, NH4HCO3 included in the slurry spontaneously produced ammonia and carbon dioxide gas bubbles during spray drying. These gases can gather in the center of the particle due to the surface tension, resulting in the formation of hollow HA microspheres. At the same time, internal pressure is built up in the droplet by the gas bubbles. If the shell is porous, this pressure would be released and a hollow sphere would be formed. The formation process of hollow microspheres can be schematically illustrated in Fig. 3 [11,14]. However, with increasing amount of
NH4HCO3, the structure of hollow HA microspheres became less uniform. Fig. 4 shows the SEM micrographs of hollow HA microspheres prepared by incorporating 7 wt.% NH4HCO3 into the slurry. It can be seen clearly that a hollow microsphere has a porous shell and the pore size is widely distributed. This may be attributed to the generation of gases from the decomposition of NH4HCO3 that are released through the shell of the microsphere. Although microspheres prepared with 7 wt.% NH4HCO3 have a high porosity and surface area, they exhibited low strength and deviated from spherical morphology during spray drying. 3.2. Phase composition of hollow microspheres The XRD patterns of the spray dried hollow microspheres are shown in Fig. 5. It can be seen that the microspheres have a low crystallinity, which is expected since the synthesis is performed at a low temperature (less than 200 °C) and no impurity phases are detected. This indicates that the hollow microspheres prepared by this method have a high purity. After sintering at 800 °C for 1 h, there are no significant changes in phase composition of hollow microspheres except that its degree of crystalline order increases a little. The crystallite size of the microspheres is about 30 nm calculated by using Scherrer formula. While XRD results show no major differences between the spray dried microspheres and pure HA (PDF #9-432), FTIR analysis (Fig. 6) showed slight compositional changes for HA microspheres before and after thermal treatment. FTIR spectra shown in Fig. 6 were carried out in order to further study the composition of HA microspheres before and after sintering. The existence of some NH4HCO3 peaks at 3131.15 cm− 1 (Fig. 6a) shows that there is some residual NH4HCO3 in the microspheres after drying at 180 °C for 1 d. However, these peaks disappear in Fig. 6b, which indicates that NH4HCO3 can be removed from the HA microspheres through sintering at 500 °C for 1 h. In addition, the band at 1384.01 cm− 1 ascribed to a carbonate vibrational mode indicates that carbonate was incorporated into the HA crystal [15]. It can be seen clearly from structure by replacing OH− or PO3− 4
Fig. 4. SEM micrographs of hollow HA microspheres with 7 wt.% NH4HCO3.
R. Sun et al. / Materials Science and Engineering C 29 (2009) 1088–1092
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Table 1 Particle sizes and specific surface area (ST) of the samples.
Fig. 5. X-ray diffraction patterns of HA microspheres after (a) drying at 180 °C for 1 d and (b) sintering at 800 °C for 1 h.
Sample
d10 (µm)
d50 (µm)
d90 (µm)
Mean (µm)
ST (m2/g)
3% NH4HCO3 3% NH4HCO3 of sintering 5% NH4HCO3 5% NH4HCO3 of sintering
1.77 1.94 1.66 2.22
3.89 4.53 3.72 4.87
6.99 8.38 6.99 9.04
4.14 4.85 4.05 5.27
47.4 59.4 80.0 68.6
when HA is used as a bone substitute [15,19]. Therefore, carbonated HA has attracted much attention in recent years [20,21]. 3.3. Size distribution and surface area of hollow microspheres
Fig. 6. FTIR spectra for HA microspheres after (a) drying at 180 °C for 1 d and (b) sintering at 500 °C for 1 h.
Fig. 6b that the CO2− cannot be removed completely even after 3 sintering at 500 °C. The carbonate might come from the carbon dioxide decomposed from NH4HCO3 and dissolved in the HA slurry. Besides, the carbon dioxide in atmosphere may also favor the formation of carbonate while stirring and reaction processes. In fact, biological apatites have multiple substitutions and deficiencies at all ionic sites [16]. Among them, carbonate substituted apatite is of particular importance, because biological apatites contain 4–6% carbonate by weight [17,18]. Some researchers think that substitution of carbonate into the apatite may lead to a higher solubility, which is important
In order to measure the particle size distribution of the produced microspheres, a particle size analyzer was employed. Particle size distribution data for the HA microspheres prepared with different ammonium bicarbonate concentrations are shown in Fig. 7. The results indicate that most of the particles range in size from 1–10 µm. Furthermore, we can see from Table 1 that the mean particle sizes of the microspheres with the addition of 3 wt.% and 5 wt.% NH4HCO3 before and after sintering are 4.14 and 4.05 µm, respectively, which shows that the content of NH4HCO3 has a low influence on the particle size of the produced microspheres. However, the particle size of the microspheres increased slightly after sintering. This may be due to the expansion of the microspheres induced by the release of gases such as CO2, NH3 and H2O. As is shown in Table 1, the specific surface areas of the hollow microspheres with the addition of 5 wt.% NH4HCO3 are higher than that of 3 wt.% NH4HCO3 both before and after thermal treatment. This may be due to the higher NH4HCO3 content that produces higher levels of porosity. The specific surface area of the hollow microspheres with the addition of 5 wt.% NH4HCO3 decreased a little after sintering at 500 °C due to coarsening and grain growth of the HA crystallites. However, the specific surface area of HA microspheres with 3 wt.% NH4HCO3 increased slightly after sintering. This is because the porosity of the microspheres increased somewhat due to the further release of the gases, while this had little influence on the microspheres of 5 wt.% NH4HCO3 which already had a high porosity before sintering. These hollow HA microspheres with high surface area can be used as drug carriers because they can have a high drug loading.
Fig. 7. Particle size distributions of the produced microspheres.
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Fig. 8. N2 adsorption–desorption isotherm and BJH (Barrett–Joyner–Halenda) pore size distribution of the sample.
It is known that different materials have different adsorption– desorption isotherms and different shape of hysteresis loops, which shows the difference of the pore structure of porous solid materials. As shown in Fig. 8, the nitrogen adsorption–desorption isotherm of the hollow microspheres with the addition of 5 wt.% NH4HCO3 after sintering shows type II isotherm behavior with a hysteresis loop at a high relative pressure (PS / P0). This indicates that the prepared microspheres have various pore sizes distribution and multilayer adsorption occurs. We also note that the adsorption capacity increases significantly when the PS / P0 is higher than 0.8, which is interrelated with the middle and large pores of the hollow microspheres. From the pore size distribution (Fig. 8), we can see that the prepared hollow HA microspheres are mainly composed of mesopores (2–50 nm) with the maximum centered on about 20 nm. In addition, the total volume of the microspheres is about 0.411 ml/g. From the above analysis, we can see that the HA microspheres prepared in this study not only have a hollow inner structure but also have high surface area and porosity. The microspheres with high surface area and porosity may have high adsorption ability and bioactivity. Therefore, these hollow HA microspheres will have wide applications in many fields such as drug carriers and separation and purification. 4. Conclusions In this study, we produced hollow HA microspheres with open pores on their surface by using a simple spray drying method and ammonium bicarbonate was employed as a gas foaming agent. The hollow HA microspheres have a high porosity and surface area when
the concentration of ammonium bicarbonate is about 3 wt.%–5 wt.% and the mean particle size is around 5 µm. These hollow HA microspheres can be potentially used in drug delivery and separation and purification fields. References [1] Y. Mizushima, T. Ikoma, J. Tanaka, K. Hoshi, T. Ishihara, Y. Ogawa, A. Ueno, J. Control. Release 110 (2006) 260. [2] L.M. Sun, C.C. Berndt, K.A. Khor, H.N. Cheang, K.A. Gross, J. Biomed. Mater. Res. 62 (2002) 228. [3] C.C. Chen, T.H. Huang, C.T. Kao, S.J. Ding, J. Biomed. Materi. Res. Part B: Appl. Biomater. 78B (2006) 146. [4] W. Suchanek, M. Yoshimura, J. Mater. Res. 13 (1998) 94. [5] N.Y. Mostafa, Mater. Chem. Phys. 94 (2005) 333. [6] W. Paul, C.P. Sharma, J. Mater. Sci., Mater. Med. 10 (1999) 383. [7] V.S. Komlev, S.M. Barinov, E.V. Koplik, Biomaterials 23 (2002) 3449. [8] W. Paul, J. Nesamony, C.P. Sharma, J. Biomed. Mater. Res. 61 (2002) 660. [9] M. Sivakumar, K. Panduranga Rao, J. Biomed. Mater. Res. 65A (2003) 222. [10] P. Luo, T.G. Nieh, Biomaterials 17 (1996) 1959. [11] P. Luo, T.G. Nieh, S, Mater. Sci. Eng., C 3 (1995) 75. [12] A.J. Wang, Y.P. Lu, R.X. Sun, Mater. Sci. Eng., A 460–461 (2007) 1. [13] J. Bertling, J. Blomer, R. Kummel, Chem. Eng. Technol. 27 (2004) 829. [14] T.K. Kim, J.J. Yoon, D.S. Lee, T.G. Park, Biomaterials 27 (2006) 152. [15] R. Murugan, S. Ramakrishma, Acta Biomater. 2 (2006) 201. [16] M.E. Fleet, X.Y. Liu, Biomaterials 26 (2005) 7548. [17] T.h. Leventouri, Biomaterials 27 (2006) 3339. [18] E. Landi, G. Celotti, G. Logroscino, A. Tampieri, J. Eur. Ceram. Soc. 23 (2003) 2931. [19] S. Cai, Y.W. Wang, H. Lv, Z.Z. Peng, K.D. Yao, Ceram. Int. 31 (2005) 135. [20] R.K. Tang, Z.J. Henneman, G.H. Nancollas, J. Cryst. Growth 249 (2003) 614. [21] A. Slosarczyk, Z. Paszkiewicz, C. Paluszkiewicz, J. Mol. Struct. 744–747 (2005) 657–661.
Contents lists available at ScienceDirect
Materials Science and Engineering C j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / m s e c
Short communication
Preparation and characterization of hollow hydroxyapatite microspheres by spray drying method Ruixue Sun a, Yupeng Lu b,⁎, Kezheng Chen a a b
College of Materials Science and Engineering, Qingdao University of Science and Technology, Qingdao 266042, China School of Materials Science and Engineering, Shandong University, Jinan 250061, China
a r t i c l e
i n f o
Article history: Received 5 November 2007 Received in revised form 30 July 2008 Accepted 7 August 2008 Available online 22 August 2008 Keywords: Hydroxyapatite Hollow microspheres Spray drying Characterization
a b s t r a c t Hollow hydroxyapatite (Ca10(PO4)6(OH)2) microspheres were prepared using a simple spray drying method. The incorporation of ammonium bicarbonate could produce carbon dioxide and ammonia gas bubbles during the spraying, and thus created a hollow inner structure in the resultant microspheres. The hollow microspheres prepared using different amounts of ammonium bicarbonate were also characterized. These microspheres were composed of nanoparticles with an average crystallite size of 15 nm. A high surface area (80 m2/g) and porosity of the microspheres could be achieved when the concentration of ammonium bicarbonate was about 5 wt.%. Fourier transform infrared results showed that CO2− 3 was incorporated into the HA microspheres. These hollow microspheres have many potential uses such as injectable drug-delivery carriers. © 2008 Published by Elsevier B.V.
1. Introduction Hydroxyapatite (HA) is widely used in areas of orthopaedic and dental surgery, separation and purification because of its unique properties related to good biocompatibility, osteoconduction and excellent adsorption properties [1]. There are many reports about HA coatings and HA composite bioceramic materials [2–4]. However, there are few reports about HA microspheres, especially hollow HA microspheres [5,6]. HA microspheres have many unusual properties such as large specific surface area, good flowability and so on. HA microspheres have received much attention owing to its special structure, changeable properties and wide range of applications. Recently, several methods have been developed to prepare HA microspheres with dimensions ranging from submicron to micron size for use in sustained-release drug-delivery systems [6–9]. The spray drying method is particularly attractive because of its widespread use and relative ease of operation. P. Luo et al. prepared HA powders with controlled morphology including doughnut shapes, solid spheres or hollow spheres by using this spray drying method [10,11]; Y. Mizushima et al. fabricated spherical porous HA microparticles as an injectable drug carrier by the spray drying method [1]. And the in vivo experiment results suggest the possibility of the HA microspheres used as an excellent drug carrier for sustained-release. Compared with the simple spherical HA particles, the HA microspheres with porous and hollow structure have more excellent
⁎ Corresponding author. Tel./fax: +86 531 88395966. E-mail address: [email protected] (Y. Lu). 0928-4931/$ – see front matter © 2008 Published by Elsevier B.V. doi:10.1016/j.msec.2008.08.010
properties such as low density and large encapsulation capacity. However, there have been few reports of the hollow HA microspheres prepared by spray drying method, which incorporate an adequate amount of drugs and can release them slowly [12,13]. In this study, we fabricated hollow HA microspheres by the spray drying method and ammonium bicarbonate was used as a gas foaming agent, which can generate carbon dioxide and ammonia gas bubbles during the spraying. The resultant hollow microspheres prepared with different amounts of ammonium bicarbonate were also characterized. 2. Materials and methods 2.1. Preparation of the HA microspheres The feedstock HA precipitates were prepared by using a wet method according to the following reaction: 10Ca(NO 3 ) 2 + 6 (NH4)2HPO4 +8NH4OH→Ca10(PO4)6(OH)2 +20NH4NO3 +6H2O. Briefly, aqueous solutions of Ca(NO3)2·4H2O and (NH4)2HPO4 with Ca/P ratio of 1.67 were prepared, respectively. The pH of the two solutions was adjusted to 10–11 by using NH4OH. Under vigorous stirring, the (NH4)2HPO4 solution was added to the Ca(NO3)2·4H2O solution and the resultant HA precipitate was aged at room temperature. Then the precipitates were washed with distilled water several times to remove nitrate ions and ammonium ions. After removing the supernatant from the aged precipitates, distilled water was added to dilute the precipitates to some extent. Ammonium bicarbonate (NH4HCO3) was dissolved in distilled water at different concentrations ranging from 1– 7 wt.% and was added to the HA slurry under magnetic stirring. Then they were spray dried using a GPW120-II small-type spray dryer. In
R. Sun et al. / Materials Science and Engineering C 29 (2009) 1088–1092
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Fig. 1. SEM micrographs of hollow HA microspheres with 3 wt.% NH4HCO3.
brief, the mixture was atomized at a pressure of 15 L/min and a flow rate of 400 ml/h, while the inlet and outlet temperatures of the nozzle were adjusted to 170 °C and 100 °C, respectively. The product was dried at 180 °C for 1 d, or calcined at 500 °C and 800 °C for 1 h, respectively. 2.2. Characterization The morphology of the spray dried HA microspheres was examined by scanning electron microscope (SEM) (a Hitachi S-570, Japan) and field emission SEM (a JEOL JSM6700F microscope, Japan). The phase analysis was carried out using a Japan Rigaku D/max-γB X-
ray diffractometer (XRD), with a scan speed of 4°/min between 10 and 60 °2θ angle, operated at 40 kV and 100 mA. A Nicolet Nexus-470 Fourier transform infrared (FTIR) spectroscope was used to characterize the functional groups of the microspheres. The particle size distribution and mean particle size were measured using a LS13320 Laser Diffraction Particle Size Analyzer (Beckman-Coulter, America) and distilled water was employed as the dispersion medium. The diameter measurement error of this equipment is equal to about 3%. The specific surface area and pore size distribution were determined by the Brunauer–Emmett–Teller (BET) method using a Coulter SA3100 Surface Area Analyzer after being degassed at 200 °C for 2 h and
Fig. 2. FE-SEM micrographs of HA microspheres.
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Fig. 3. Schematic illustration of the formation of hollow microspheres.
using nitrogen as the absorbent. The surface area measurement error of this equipment is equal to about 3%. 3. Results and discussion 3.1. Microstructure of the hollow HA microspheres Fig. 1 shows the SEM micrographs of hollow HA microspheres prepared by spray drying. It can be seen from Fig. 1a that the spray dried microparticles are spherical and there are “black” points on the surface of almost all microspheres. At higher magnification (Fig. 1a, b and c), we can see that the “black” points are open pores on the surface of the microspheres and the pore diameter ranges from approximately 0.2–1.5 µm. The hollow structure of the microspheres can be clearly observed from Fig. 1c and d. The hollow region appeared as regular sphere located at the center of a porous microsphere shell. In addition, Fig. 1 shows that most of the microparticles kept their spherical morphology after spray drying, which indicates that the hollow microspheres have sufficient strength for further handling and processing. The FE-SEM micrographs of HA microspheres are shown in Fig. 2. It can be seen that the shell of the hollow HA microsphere is composed of homogeneous HA crystallites. In fact, spray dried HA microspheres have already been reported by some researchers [1,10], but there have been no reports about hollow HA microsphere fabricated using NH4HCO3 as a gas foaming agent. In the present study, different amounts of NH4HCO3 were added into the HA slurry before spray drying to optimize hollow HA microparticle formation. Under continuous stirring, NH4HCO3 included in the slurry spontaneously produced ammonia and carbon dioxide gas bubbles during spray drying. These gases can gather in the center of the particle due to the surface tension, resulting in the formation of hollow HA microspheres. At the same time, internal pressure is built up in the droplet by the gas bubbles. If the shell is porous, this pressure would be released and a hollow sphere would be formed. The formation process of hollow microspheres can be schematically illustrated in Fig. 3 [11,14]. However, with increasing amount of
NH4HCO3, the structure of hollow HA microspheres became less uniform. Fig. 4 shows the SEM micrographs of hollow HA microspheres prepared by incorporating 7 wt.% NH4HCO3 into the slurry. It can be seen clearly that a hollow microsphere has a porous shell and the pore size is widely distributed. This may be attributed to the generation of gases from the decomposition of NH4HCO3 that are released through the shell of the microsphere. Although microspheres prepared with 7 wt.% NH4HCO3 have a high porosity and surface area, they exhibited low strength and deviated from spherical morphology during spray drying. 3.2. Phase composition of hollow microspheres The XRD patterns of the spray dried hollow microspheres are shown in Fig. 5. It can be seen that the microspheres have a low crystallinity, which is expected since the synthesis is performed at a low temperature (less than 200 °C) and no impurity phases are detected. This indicates that the hollow microspheres prepared by this method have a high purity. After sintering at 800 °C for 1 h, there are no significant changes in phase composition of hollow microspheres except that its degree of crystalline order increases a little. The crystallite size of the microspheres is about 30 nm calculated by using Scherrer formula. While XRD results show no major differences between the spray dried microspheres and pure HA (PDF #9-432), FTIR analysis (Fig. 6) showed slight compositional changes for HA microspheres before and after thermal treatment. FTIR spectra shown in Fig. 6 were carried out in order to further study the composition of HA microspheres before and after sintering. The existence of some NH4HCO3 peaks at 3131.15 cm− 1 (Fig. 6a) shows that there is some residual NH4HCO3 in the microspheres after drying at 180 °C for 1 d. However, these peaks disappear in Fig. 6b, which indicates that NH4HCO3 can be removed from the HA microspheres through sintering at 500 °C for 1 h. In addition, the band at 1384.01 cm− 1 ascribed to a carbonate vibrational mode indicates that carbonate was incorporated into the HA crystal [15]. It can be seen clearly from structure by replacing OH− or PO3− 4
Fig. 4. SEM micrographs of hollow HA microspheres with 7 wt.% NH4HCO3.
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Table 1 Particle sizes and specific surface area (ST) of the samples.
Fig. 5. X-ray diffraction patterns of HA microspheres after (a) drying at 180 °C for 1 d and (b) sintering at 800 °C for 1 h.
Sample
d10 (µm)
d50 (µm)
d90 (µm)
Mean (µm)
ST (m2/g)
3% NH4HCO3 3% NH4HCO3 of sintering 5% NH4HCO3 5% NH4HCO3 of sintering
1.77 1.94 1.66 2.22
3.89 4.53 3.72 4.87
6.99 8.38 6.99 9.04
4.14 4.85 4.05 5.27
47.4 59.4 80.0 68.6
when HA is used as a bone substitute [15,19]. Therefore, carbonated HA has attracted much attention in recent years [20,21]. 3.3. Size distribution and surface area of hollow microspheres
Fig. 6. FTIR spectra for HA microspheres after (a) drying at 180 °C for 1 d and (b) sintering at 500 °C for 1 h.
Fig. 6b that the CO2− cannot be removed completely even after 3 sintering at 500 °C. The carbonate might come from the carbon dioxide decomposed from NH4HCO3 and dissolved in the HA slurry. Besides, the carbon dioxide in atmosphere may also favor the formation of carbonate while stirring and reaction processes. In fact, biological apatites have multiple substitutions and deficiencies at all ionic sites [16]. Among them, carbonate substituted apatite is of particular importance, because biological apatites contain 4–6% carbonate by weight [17,18]. Some researchers think that substitution of carbonate into the apatite may lead to a higher solubility, which is important
In order to measure the particle size distribution of the produced microspheres, a particle size analyzer was employed. Particle size distribution data for the HA microspheres prepared with different ammonium bicarbonate concentrations are shown in Fig. 7. The results indicate that most of the particles range in size from 1–10 µm. Furthermore, we can see from Table 1 that the mean particle sizes of the microspheres with the addition of 3 wt.% and 5 wt.% NH4HCO3 before and after sintering are 4.14 and 4.05 µm, respectively, which shows that the content of NH4HCO3 has a low influence on the particle size of the produced microspheres. However, the particle size of the microspheres increased slightly after sintering. This may be due to the expansion of the microspheres induced by the release of gases such as CO2, NH3 and H2O. As is shown in Table 1, the specific surface areas of the hollow microspheres with the addition of 5 wt.% NH4HCO3 are higher than that of 3 wt.% NH4HCO3 both before and after thermal treatment. This may be due to the higher NH4HCO3 content that produces higher levels of porosity. The specific surface area of the hollow microspheres with the addition of 5 wt.% NH4HCO3 decreased a little after sintering at 500 °C due to coarsening and grain growth of the HA crystallites. However, the specific surface area of HA microspheres with 3 wt.% NH4HCO3 increased slightly after sintering. This is because the porosity of the microspheres increased somewhat due to the further release of the gases, while this had little influence on the microspheres of 5 wt.% NH4HCO3 which already had a high porosity before sintering. These hollow HA microspheres with high surface area can be used as drug carriers because they can have a high drug loading.
Fig. 7. Particle size distributions of the produced microspheres.
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Fig. 8. N2 adsorption–desorption isotherm and BJH (Barrett–Joyner–Halenda) pore size distribution of the sample.
It is known that different materials have different adsorption– desorption isotherms and different shape of hysteresis loops, which shows the difference of the pore structure of porous solid materials. As shown in Fig. 8, the nitrogen adsorption–desorption isotherm of the hollow microspheres with the addition of 5 wt.% NH4HCO3 after sintering shows type II isotherm behavior with a hysteresis loop at a high relative pressure (PS / P0). This indicates that the prepared microspheres have various pore sizes distribution and multilayer adsorption occurs. We also note that the adsorption capacity increases significantly when the PS / P0 is higher than 0.8, which is interrelated with the middle and large pores of the hollow microspheres. From the pore size distribution (Fig. 8), we can see that the prepared hollow HA microspheres are mainly composed of mesopores (2–50 nm) with the maximum centered on about 20 nm. In addition, the total volume of the microspheres is about 0.411 ml/g. From the above analysis, we can see that the HA microspheres prepared in this study not only have a hollow inner structure but also have high surface area and porosity. The microspheres with high surface area and porosity may have high adsorption ability and bioactivity. Therefore, these hollow HA microspheres will have wide applications in many fields such as drug carriers and separation and purification. 4. Conclusions In this study, we produced hollow HA microspheres with open pores on their surface by using a simple spray drying method and ammonium bicarbonate was employed as a gas foaming agent. The hollow HA microspheres have a high porosity and surface area when
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