Solution synthesis of hydroxyapatite designer particulates
Richard E. Riman a,*, Wojciech L. Suchanek a,1, Kullaiah Byrappa a,b, Chun-Wei Chen a,Pavel Shuk a,2, Charles S. Oakes a
aDepartment of Ceramic and Materials Engineering, Rutgers, The State University of New Jersey, 607 Taylor Road, Piscataway,
NJ 08854-8065, USAbDepartment of Geology, University of Mysore, P.B. No. 21, Mysore 570 006, India
Received 30 January 2001; accepted 12 October 2001
Abstract
This paper reviews our research program for intelligent synthesis of hydroxyapatite (HAp) designer particulates by low-
temperature hydrothermal and mechanochemical–hydrothermal methods. Our common starting point for hydrothermal
crystallization is the generation and validation of equilibrium diagrams to derive the relationship between initial reaction
conditions and desired phase assemblage(s). Experimental conditions were planned based on calculated phase boundaries in the
system CaO–P2O5–NH4NO3–H2O at 25–200 jC. HAp powders were then hydrothermally synthesized in stirred autoclaves at
50–200 jC and by the mechanochemical–hydrothermal method in a multi-ring media mill at room temperature. The
synthesized powders were characterized using X-ray diffraction, infrared spectroscopy, thermogravimetry, chemical analysis
and electron microscopy. Hydrothermally synthesized HAp particle morphologies and sizes were controlled through
thermodynamic and non-thermodynamic processing variables, e.g. synthesis temperature, additives and stirring speed.
Hydrothermal synthesis yielded well-crystallized needle-like HAp powders (size range 20–300 nm) with minimal levels of
aggregation. Conversely, room-temperature mechanochemical–hydrothermal synthesis resulted in agglomerated, nanosized
(f 20 nm), mostly equiaxed particles regardless of whether the HAp was stoichiometric, carbonate-substituted, or contained
both sodium and carbonate. The thermodynamic model appears to be applicable for both stoichiometric and nonstoichiometric
compositions. The mechanochemical–hydrothermal technique was particularly well suited for controlling carbonate
substitution in HAp powders in the range of 0.8–12 wt.%. The use of organic surfactants, pH or nonaqueous solvents
facilitated the preparation of stable colloidal dispersions of these mechanochemical–hydrothermal-derived HAp nanopowders.
D 2002 Elsevier Science B.V. All rights reserved.
Keywords: Hydrothermal technique; Mechanochemical synthesis; Phase diagram; Thermodynamic modeling; Hydroxyapatite; Solution
processing
1. Introduction
Hydroxyapatite (HAp) with the chemical formula
Ca10(PO4)6(OH)2 has been extensively used in med-
icine for implant fabrication owing to its similarity
with mineral constituents found in hard tissue (i.e.
teeth and bones) [1,2]. Because of its high level of
biocompatibility, it is commonly the material of
0167-2738/02/$ - see front matter D 2002 Elsevier Science B.V. All rights reserved.
PII: S0167 -2738 (02 )00545 -3
* Corresponding author. Tel.: +1-732-445-4946; fax: +1-732-
445-6264.
E-mail address: [email protected] (R.E. Riman).1 Present address: Sawyer Research Products, Incorporated,
35400 Lakeland Boulevard, Eastlake, OH 44095, USA.2 Present address: Rosemount Analytical Incorporated, 1201
North Main Street, P.O. Box 901, Orrville, OH 4467-0901, USA.
www.elsevier.com/locate/ssi
Solid State Ionics 151 (2002) 393–402
choice for fabrication of dense and porous bioceram-
ics [3]. Unfortunately, due to low mechanical reliabil-
ity, especially in aqueous environments [4], HAp
bioceramics cannot be used for heavy load-bearing
applications. Thus, general usages include biocompat-
ible phase reinforcement in composites, coatings on
metal implants and granular fill for direct incorpora-
tion into human tissues [1–3]. Non-medical applica-
tions of HAp include packing media for column
chromatography, gas sensors, catalysts and host mate-
rial for lasers [5]. Properties of HAp, including bio-
activity, biocompatibility, solubility, sinterability,
castability, fracture toughness and adsorption can be
tailored over wide ranges by control of particle
composition (e.g. lattice substitution), particle size
and morphology [1–3,6]. For these reasons, it is of
great importance to develop inexpensive HAp syn-
thesis methods focused on the precise control of
particle size, morphology and chemical composition.
Low-temperature solution techniques appear to be
particularly well suited to achieve this goal. Aqueous
slurries, solutions, or gels can be transformed into the
desired crystalline phases via hydrothermal methods
in a single process step under mild reaction condi-
tions, typically at < 350 jC and < 150 atm [7].
Because the reactions are solution-mediated, particle
size and morphology can be controlled by experimen-
tal strategies that regulate nucleation, growth and
aging processes. Conversely, mechanochemical syn-
thesis is a solid-state method that takes advantage of
the perturbation of surface-bonded species by pressure
to enhance thermodynamic and kinetic reactions [8].
Pressure can be applied at room temperature by mill-
ing equipment ranging from low-energy ball mills to
high-energy stirred mills (e.g. attrition, planetary and
vibratory). The main advantages of mechanochemical
ceramic powder synthesis are simplicity and low cost.
A variety of ceramic materials can be prepared by this
technique, viz. CaSiO3 [9], PbTiO3 [10] and
0.9Pb(Mg1/3Nb2/3)O3–0.1PbTiO3 [11]. HAp has also
been produced by this method; however, previous
studies produced poorly crystalline, highly nonstoi-
chiometric and thermally unstable HAp [12,13].
Wet mechanochemical synthesis, referred to as
mechanochemical–hydrothermal synthesis, utilizes
an aqueous solution as a reaction medium. Mechano-
chemical activation of slurries can generate local
zones of high temperatures (up to 450–700 jC) and
high pressures due to friction effects and adiabatic
heating of gas bubbles (if present in the slurry), while
the bulk system is close to room temperature [14].
Consequently, the thermodynamics of the local reac-
tion environment favor reactions which may other-
wise be kinetically inhibited at the bulk system
temperature and pressure [15]. Low-cost raw materials
can be used for most hydrothermal and mechano-
chemical – hydrothermal processes which, when
coupled with the use of conventional autoclaves and
mills, can lead toward the development of low-cost
powder synthesis processes.
Several commercial hydrothermal technologies
have been developed for producing ceramic powders
such as alumina, stabilized zirconia, dicalcium silicate
and barium titanate [16]. Nanosized particulates of
ceria, zirconia, alumina, tin oxide, zinc oxide and
ferrites with a variety of morphologies have been
synthesized via commercial mechanochemical meth-
ods [17]; however, we are not aware of any commer-
cial mechanochemical–hydrothermal processes.
Our research at Rutgers University has focused on
mild solution conditions (less than 350 jC) for the
synthesis of HAp and other particulates. Reactions
above this temperature are seldom used mainly due to
limitations introduced by the material construction of
the reactor vessels, such as product contamination due
to reactor corrosion and safety issues related to reactor
fatigue.
2. Overall goals
Our goal is to develop hydrothermal and mecha-
nochemical–hydrothermal synthesis methods suitable
for the commercial production of HAp designer par-
ticulates whose composition, size and morphology are
controlled under mild reaction conditions. From the
scientific perspective, we wish to develop hydrother-
mal and mechanochemical–hydrothermal synthesis
methods through the application of fundamental prin-
ciples as opposed to time-consuming trial and error
empiricism. Our rational approach is to calculate
equilibrium phase assemblages as a function of typical
hydrothermal processing variables using theoretical or
semi-theoretical thermodynamic models. Hydrother-
mal and mechanochemical–hydrothermal tests are
then designed to validate the computed equilibrium
R.E. Riman et al. / Solid State Ionics 151 (2002) 393–402394
diagrams with a focus on finding the optimum reac-
tion conditions for the phase of interest. From the
validated diagrams, we utilize a range of processing
variables such as heating rate, stirring rates, ionic
strength and system composition to explore opportu-
nities to control reaction kinetics and crystal size and
morphology. This methodology enables us to design
experiments with a significantly reduced level of risk
and expenditure in time, personnel and materials.
3. Experimental methods
3.1. Hydrothermal synthesis of HAp powders
Aqueous solutions of calcium nitrate (Ca(NO3)2),
diammonium hydrogen phosphate ((NH4)2HPO4),
ammonium dihydrogen phosphate (NH4H2PO4),
ammonium hydroxide (NH4OH, 29%) and nitric acid
(HNO3, fuming, 90%) (all analytical grade, Fisher
Scientific) were used as reactants. Aliquots of f 3 M
Ca(NO3)2 and f 2 M (NH4)2HPO4 or f 2 M
NH4H2PO4 stock solutions were diluted with distilled
water and subsequently mixed to yield slurries with
Ca/P molar ratios between 1.25 and 1.67 and P
concentrations of 0.05–0.28 mol/(kg of H2O). The
room temperature pH was adjusted in the range from 2
to 10 using HNO3 and NH4OH. pH was measured at
25 jC using a glass electrode (Model 261S, Orion
Research).
In experiments aimed at phase diagram validation,
mixtures of the above precursor solutions were trans-
ferred to unstirred, 125-ml Teflon-lined hydrothermal
reactors (Model 4748, Parr Instrument). Each reaction
was placed in a laboratory oven for 24 h at a temper-
ature between 50 and 200 jC. In hydrothermal experi-
ments designed to assess effects of stirring on the
physicochemical properties of HAp powders, mix-
tures of precursor solutions were transferred to 1-l
Teflon-lined stirred hydrothermal reactors (Model
4531, Parr Instrument). Each reactor was heated for
24 h at a temperature between 50 and 200 jC. Stirringrates were set between 100 and 1500 rpm.
To assess the effects of additional salts and mixed
solvents on powder size and morphology, three types
of experiments were conducted. The first and simplest
consisted of reacting aqueous solutions to form amor-
phous calcium phosphate (ACP) as described above.
For the second, 1 wt.% KCl (certified ACS, Fisher
Scientific) was also added. The third type of experi-
ment was centrifugally separated and dispersed in 50
vol.% 2-propanol (certified ACS, Fisher Scientific) in
water. In each of these experiments, the Ca/P molar
ratio in the mixture was 1.67, total phosphorus was
0.05 mol/(kg of H2O) and the room temperature pH of
the initial mixture was fixed at 10.0F 0.1 using
NH4OH. Subsequently, for these size and morphology
control studies, precursor mixtures were transferred to
Teflon liners containing a magnetic stirrer bar and
placed in general purpose 125 ml Parr autoclaves.
Each autoclave was then placed in a mantle heater on
a heating–stirring plate and heated using both the
mantle heater and heating plate at 200 jC for 15 h.
The autoclave temperature was monitored using a
thermocouple inserted into a thermowell. Stirring rate
was set to a value sufficient to prevent sedimentation;
however, the stirring rate could not be quantified.
Following all experiments, the synthesized HAp
powders were washed three to six times using deion-
ized water. Washed HAp powders were either dried in
a laboratory oven at 70 jC for 24 h or freeze-dried
using a Dura Dry AP freeze drier (FTS Kinetics).
3.2. Mechanochemical–hydrothermal synthesis of
HAp powders
Calcium hydroxide (Ca(OH)2), calcium carbonate
(CaCO3) and (NH4)2HPO4 (all analytical grade pow-
ders, Alfa Aesar) were used as reactants for mecha-
nochemical–hydrothermal synthesis of stoichiometric
HAp and CO3-substituted HAp. Sodium carbonate
(Na2CO3) (analytical grade powder, Alfa Aesar) was
used instead of CaCO3 for synthesis of HAp with
coupled CO3- and Na-substitution. Targeted chemical
compositions corresponded to x = 0, 1, 2, or 3 in
Ca10 � x + y(CO3)x(PO4)6 � x(OH)2 � x + 2y (hereafter
denoted as CO3HAp) and x = 0, 1, 2, 3 and 4 in
Ca10 � xNa2x/3(PO4)6 � x(CO3)x(H2O)x(OH)2 � x/3
(hereafter denoted as NaCO3HAp). Both CO3HAp
and NaCO3HAp powders were synthesized according
to the following procedure. First, 350 ml of an
aqueous suspension of 26–32 g of Ca(OH)2 and
CaCO3 (or Na2CO3) as required by stoichiometry
was prepared in a 500-ml glass beaker. Subsequently,
a stoichiometric amount of (NH4)2HPO4 (20–27 g)
was added slowly to the same beaker while stirring
R.E. Riman et al. / Solid State Ionics 151 (2002) 393–402 395
vigorously for about 10 min. Each slurry contained
about 13 wt.% solids and the initial pH ranged
between 10.0 and 11.3. The slurries were then poured
into a laboratory-scale multi-ring media mill (model
MIC-0, NARA Machinery) equipped with a zirconia
liner and zirconia ring grinding media. Grinding was
carried out under air at a rotation speed of 1500 rpm
for 1 h and then at 800 rpm for 4 h. The temperature
during grinding ranged between 29–35 jC at 1500
rpm and 25–32 jC at 800 rpm. The solid products
were then put through two to six washing cycles, each
of which consisted of shaking the solid with deionized
water followed by centrifuging at 4500 rpm for 30
min. The washed powders were either dried in an
oven at 70 jC for 24 h or freeze-dried.
3.3. Characterization of the materials
X-ray diffraction (XRD) characterization of all
prepared powders was conducted using a Kristalloflex
D-500 diffractometer (Siemens Analytical X-ray
Instrument) with Ni-filtered Cu Ka radiation over
the 2h range of 10–70j at a scan rate of 2.4j/min.
The sampling interval was 0.05j. Infrared spectra
(FTIR) of the HAp powders were obtained using a
Perkin Elmer model 1720-X spectrometer. Pellets for
FTIR analysis were prepared from 1:150 HAp–KBr
mixtures (by weight), which were ground in a mortar
and pestle for 15 min and pressed into pellets using a
hand press. Thermogravimetric analyses (TGA) of as-
prepared HAp powders were conducted at 5j/min in
flowing air (30 ml/min.) over a temperature range of
25–1000 jC using a Perkin Elmer model TGA-7.
Chemical analyses for calcium and phosphorus of
selected batches of the as-prepared powders were
conducted by X-ray fluorescence (XRF, by Oneida
Research Services). Carbonate was determined by
carbon coulometry at Pennsylvania State University,
University Park, PA (see Acknowledgement). Specific
surface area measurements were made using the BET
method utilizing adsorption of N2 gas (purity 99.99%,
Matheson) at � 196 jC (Coulter Surface Area Ana-
lyzer SA 3100, Coulter). Equivalent spherical diame-
ters, also called BET particle diameters (dBET), were
estimated from the nitrogen adsorption isotherms
using the equation: dBET = 6/(q�Sw), where q is the
density of stoichiometric HAp (3.156 g/cm3) and Sw is
specific surface area. The degree of agglomeration
and HAp particle sizes were determined using a field-
emission scanning electron microscope at 1–5 kV
with a working distance of 2–12 mm (FESEM, Model
DSM 962, Gemini, Carl Zeiss) and a transmission
electron microscope (TEM, Model EM-002B, Interna-
tional Scientific Instruments) at 100–200 kV. Particle
size distributions were determined by dynamic light
scattering at a wavelength of 632.8 nm (DLS, model
DLS-700, Otsuka Electronics). For the DLS measure-
ments, the powders were dispersed either in pure
water or in ethanol. The stoichiometric HAp powders
were additionally dispersed either in aqueous solu-
tions of organic surfactants, such as sodium dodecyl-
benzenesulphonate (SDBS, C18H29SO3Na) (Aldrich),
hexadecyltrimethyl-ammonium bromide (HTAB,
C16H33 N(CH3)3Br) (Fluka), or in aqueous ammonia
(Fisher Scientific) at pH’s ranging between 9 and 11.
4. Thermodynamic modeling and model validation
Experimental conditions for hydrothermal synthe-
sis of HAp were based upon calculated phase boun-
daries in the system CaO–P2O5–NH4NO3–H2O
between 25 and 200 jC. Phase diagrams were calcu-
lated at each experimental temperature using commer-
cial thermochemical process simulation software [18].
The thermodynamic foundation for the algorithms in
the software has been presented elsewhere [19].
Briefly, standard state chemical potentials at the
temperature of interest are calculated either from
temperature-dependent equilibrium constant functions
for the relevant equilibria (Table 1) or through temper-
ature-dependent functions for each species’ standard
state heat capacities—both used in conjunction with
solute and solvent activity coefficients. The equations
used to calculate the latter quantities were documented
by Lencka and Riman [19].
The standard state quantities (DGfj, DHfj, Sfj) forthe solute species were generally taken from Shock et
al. [20–22]; however, in some cases the values are
proprietary to OLI (e.g. for CaPO4� , CaH2PO4
+ and
CaNO3� ). Changes in solute free energies were
calculated as functions of temperature and pressure
using the modified Helgeson–Kirkham–Flowers
(HKF) model [23]. Solid phase standard state proper-
ties were obtained from thermodynamically consistent
sources: Zhu and Sverjensky [24] for HAp and h-
R.E. Riman et al. / Solid State Ionics 151 (2002) 393–402396
TCP, Wagman et al. [25] or Veillard and Tardy [26]
for all others. Temperature-dependent functions were
fit to the heat capacity data for HAp, monetite (Mt,
CaHPO4) and brushite (CaHPO4�2H2O) [27–31];
parameters for the other solids were taken from
Veillard and Tardy [26]. Note that some standard
sources [32] of thermodynamic quantities have used
red phosphorus as the reference state for phosphorus,
whereas this study and most others have used white
phosphorus. In addition, published values of DHfj for
many calcium phosphates are highly variable [24].
While in this case, inconsistent Sfj values contributed
relatively minor errors to the calculated phase equi-
libria, the imprecision in DHfj values for HAp had a
significant effect on calculated phase boundaries.
Computed phase diagrams for hydrothermal and
mechanochemical–hydrothermal synthesis of HAp at
selected temperatures, with results from experimental
validation studies, are shown in Fig. 1. Experimental
Fig. 1. Calculated phase equilibria in the CaO–P2O5–NH4NO3–
H2O system at (a) 25 jC and (b) 200 jC as a function of precursor
concentration and pH. pH values are calculated from the model for
the temperatures shown in the figures. Initial room temperature pH
of the starting slurries have been recalculated to pH’s at the
experimental temperatures. Both diagrams show stability fields for
HAp and monetite (Mt). Experimental points represent phase
assemblages according to the legends.
Table 1
Relevant equilibria for thermodynamic computations
Solid dissolution
reactions
Solution phase
reactions
Ca(OH)2 =Ca2 + + 2OH� CaPO4
� =Ca2 + + PO43�
Ca5OH(PO4)3 = 5Ca2 + +
OH� + 3PO43�
CaH2PO4+ =Ca2 + +H2PO4
�
h-Ca3(PO4)2 = 3Ca2 + + 2PO4
3� CaNO3+ =Ca2 + +NO3
�
CaHPO4�2H2O=Ca2 + +
HPO42� + 2H2O
CaOH + =Ca2 + +OH�
CaHPO4 =Ca2 + +HPO4
2� H2O=H + +OH�
Ca(H2PO4)2�H2O=Ca2 + +
2H2PO4� +H2O
H3PO4,aq =H+ +H2PO4
�
Ca(H2PO4)2 =Ca2 + + 2H2PO4
� H2PO4� =H + +HPO4
2�
HPO42� =H + + PO4
3�
H4P2O7,aq =H+ +H3P2O7
�
H3P2O7� =H + +H2P2O7
2�
H2P2O72� =H + +HP2O7
3�
HP2O73� =H + + P2O7
4�
HNO3,aq =H+ +NO3
�
NH3,aq +H2O=NH4+ +OH�
NH4NO3,aq =NH4+ +NO3
�
P2O74� +H2O= 2PO4
3� + 2H +
R.E. Riman et al. / Solid State Ionics 151 (2002) 393–402 397
phase assemblages from the syntheses agreed well
with those predicted by the thermochemical calcula-
tions. At the phosphorus concentrations used in this
study, we have found that at 25 jC the HAp stability
field exists at equilibrium pH>4.8, whereas at 200 jCthe HAp stability field extends to an equilibrium pH
as low as 2.9. The latter pH corresponds to a room
temperature pH of about 3.8. Powders run at 200 jCand which were prepared from slurries with room
temperature pH’s lower than about 3.8 yielded only
monetite.
In addition to our experimental work, the calcu-
lated phase diagrams at elevated temperatures are also
validated by a variety of work reviewed in the
literature [3,33]. Our model confirms the well-estab-
lished stability of HAp in alkaline solutions. It can
also explain several reports on hydrothermal synthesis
of well-crystallized HAp at 200 jC at pHf 4 (as
measured at room temperature) [33].
5. Exploring processing variable space
5.1. Hydrothermal synthesis of HAp with controlled
size and morphology
Experiments were carried out at 50, 100 and 200
jC for 24 h under autogenous pressure, and starting
reaction medium pH range of 2.6–10.2, as measured
at room temperature, which corresponds to a pH range
of 1.9–7.1, as calculated at temperature. Concentra-
tion of phosphorus ranged between 0.05 and 0.28
mol/(kg of H2O). The experiments were focused on
size and morphology control of the HAp powders by
adjusting temperature, additives and non-thermody-
namic variables, such as stirring speed.
All powders prepared in alkaline solutions were
well-crystallized and phase-pure HAp, as revealed by
XRD, FTIR and TGA. Specific surface areas of HAp
powders ranged between 44 and 136 m2/g, corre-
sponding to an estimated equivalent spherical diame-
ter (dBET) of 14–44 nm. HAp crystal size increased
from 14 nm at 50 jC to 44 nm at 200 jC in the
absence of stirring, and from 15 nm at 50 jC to 38 nm
at 200 jC at the stirring rate of about 1500 rpm. The
corresponding decrease of the specific surface area
was from 136 to 44 m2/g without stirring and from
129 to 50 m2/g with stirring at 50 and 200 jC,
respectively. The aspect ratio of HAp crystals formed
in unstirred reactions was comparable to those in
stirred reactions and ranged between 2 and 5.
FESEM photographs of selected batches of HAp
crystals synthesized at 200 jC in 1 wt.% KCl (aq) and
50 vol.% 2-propanol (aq) are shown in Fig. 2. HAp
crystals synthesized in 50 vol.% 2-propanol (aq) had
low aspect ratios ranging between 2 and 3 and
diameters between 20 and 40 nm (Fig. 2a). Con-
versely, uniform, nanosized needles (dimensions of
about 20� 100–160 nm, aspect ratio of 5–8) (Fig.
2b) were formed when 1 wt.% KCl additive was used.
HAp crystals prepared under similar conditions but
Fig. 2. HAp crystals prepared hydrothermally at 200 jC for 24 h
using moderate stirring. Room temperature pH of precursor slurries
was 10. (a) Powders crystallized in 50 vol.% 2-propanol in H2O
(aq). (b) Powders crystallized with 1 wt.% KCl (aq).
R.E. Riman et al. / Solid State Ionics 151 (2002) 393–402398
without additives were f 20� 50–100 nm in size,
yielding aspect ratios between 3 and 5.
Formation of ACP prior to hydrothermal reaction
may explain why we obtained either equiaxed nano-
particles or anisotropic needles over the range of
experimental conditions. All experiments with initial
room temperature pH’s of 5 or higher precipitated ACP
upon mixing of the reactants. Since ACP has a
sufficiently low solubility such that the initial precip-
itate did not completely dissolve under the conditions
of our experiments, it is likely that the ACP particles
acted as templates for HAp crystallization via interface
reaction rate control. The formation of anisotropic
particles may be due to reaction conditions that pro-
mote a greater degree of dissolution–precipitation that
competes with interface reaction rate control. Greater
flexibility in tailoring HAp crystal size and morphol-
ogy by the hydrothermal technique could be achieved
through precipitation from homogeneous solutions
containing both Ca and P. Use of chelating agents
for Ca, such as lactic acid or EDTA, prevents forma-
tion of ACP upon mixing sources of Ca and P at room
temperature. However, published work with these
chelating agents shows that anisotropic fibers also
form. [33,34]. Thus, future work will need to identify
additions that inhibit anisotropic particle growth.
5.2. Mechanochemical–hydrothermal synthesis of
HAp with controlled chemical composition
Mechanochemical–hydrothermal synthesis was
performed at room temperature utilizing system com-
positions that the model calculations indicated would
yield phase-pure HAp powders. These conditions
were effective for synthesis of phase-pure undoped
HAp, carbonate-substituted HAp (CO3HAp), or
coupled sodium and carbonate substituted-HAp
(NaCO3HAp), as indicated by XRD, FTIR, TG and
chemical analysis. The powders contained 0.8–12
wt.% carbonate in the lattice. XRD patterns of the
as-prepared HAp and CO3HAp powders (Fig. 3)
Fig. 4. FTIR spectra of CO3HAp powders synthesized by the
mechanochemical–hydrothermal technique at room temperature
[35]. Targeted chemical compositions corresponded to x values of 0,
1, 2 and 3 in Ca10 � x + y(CO3)x(PO4)6� x(OH)2� x + 2y. (a) x= 0,
corresponding to stoichiometric HAp; (b) x= 1; (c) x= 2.
Fig. 3. XRD patterns of the CO3HAp powders synthesized by the
mechanochemical–hydrothermal technique at room temperature
[35]. Targeted chemical compositions corresponded to x values of 0,
1, 2 and 3 in Ca10� x + y(CO3)x(PO4)6� x(OH)2� x + 2y. (a) x= 0,
corresponding to stoichiometric HAp; (b) x= 1; (c) x = 2; (d) x= 3.
R.E. Riman et al. / Solid State Ionics 151 (2002) 393–402 399
indicated that most of these materials were phase-pure
HAp. FTIR and TG traces (Fig. 3a–c) generally do
not support the presence of any impurity phases.
However, at high carbonate concentrations, unreacted
calcite was detected in the as-prepared powders (Fig.
3d) indicating an upper limit of about 5 wt.% carbo-
nate incorporation in HAp by the mechanochemical–
hydrothermal technique. This upper bound can be
increased to at least 12 wt.% by coupling sodium
and carbonate substitution.
Increasing structural disorder related to increasing
carbonate substitution in the as-prepared CO3HAp
and NaCO3HAp powders was manifested by broad-
ening of the PO4-derived bands in the FTIR spectra
shown in Fig. 4. The intensity of the CO3-derived
bands in the FTIR spectra increased proportionally
with the carbonate concentration in the initial slurry
serving as evidence that the carbonate concentration
in the HAp lattice can be controlled by varying the
carbonate concentration in the precursor mixture.
Fig. 5. Electron photomicrographs of HAp powders synthesized by the mechanochemical–hydrothermal technique. (a) and (b) TEM
photomicrographs of as-prepared stoichiometric HAp; (c) TEM photomicrographs of stoichiometric HAp powder calcined in air at 900 jC for 1
h; (d) FESEM photomicrographs of a typical as-prepared NaCO3HAp powder with a carbonate concentration of 12 wt.%. Inserts in (b) and (c)
show corresponding electron diffraction patterns.
R.E. Riman et al. / Solid State Ionics 151 (2002) 393–402400
Chemical analysis confirmed the later observation.
The carbonate-bearing HAp powders contained 0.8–
12 wt.% of carbonate in the lattice.
DLS and nitrogen adsorption isotherm measure-
ments revealed that the median particle size of the
room temperature powders was in the range of 0.35–
1.6 Am with a specific surface area between 82 and
121 m2/g. FESEM and TEM confirmed that the
carbonated HAp powders consisted of mostly submi-
cron aggregates of nanosized, f 20-nm crystals (Fig.
5). Dispersing the powders in pure water (neutral pH)
resulted in micron-range average particle sizes and
broad particle size distributions. Conversely, the pow-
ders could be very well dispersed in a variety of
aqueous mixtures or pure ethanol to yield average
particle sizes of 87–130 nm. The aqueous solutions
contained organic surfactants (e.g. SDBS, HTAB) or
NH4OH sufficient to produce pH’s between 9.7 and
11.0 (Fig. 6a). A representative particle size distribu-
tion of a well-dispersed stoichiometric HAp powder is
shown in Fig. 6b.
Milling of the HAp precursor apparently acceler-
ates crystallization kinetics and enables preparation of
highly crystalline HAp within a few hours as opposed
to days or weeks as is frequently necessary for other
room-temperature processing techniques. Mechano-
chemical–hydrothermal synthesis of HAp is particu-
larly useful in accelerating the crystallization kinetics
in systems, which utilize reactant(s) with relatively
high water solubilities at 25 jC [35,36]. Thus, in
addition to facilitating HAp syntheses, the mechano-
chemical–hydrothermal method is a good means by
which to validate phase diagrams at 25 jC as opposed
to other methods that exhibit sluggish reaction
kinetics.
6. Conclusions
Thermodynamic calculations facilitate the process
engineering for hydrothermal and mechanochemical–
hydrothermal production of HAp designer particulates.
In addition, our model based upon the relatively simple
CaO–P2O5–NH4NO3–H2O system appears to apply
for both pure and doped HAp powders, encompassing
a wide range of nonstoichiometric compositions. Due
to kinetic factors, the hydrothermal technique is appro-
priate for validation of phase diagrams at elevated
temperatures, while the mechanochemical–hydrother-
mal technique is well suited for validation of phase
equilibria at room temperature. Our ability to use
equilibrium diagrams to explore processing variable
space creates a new library of technologies for the
design of commercial particulates. Our results empha-
size that the hydrothermal technique is particularly
well suited to control of HAp size and morphology
through variation of both thermodynamic and non-
thermodynamic processing variables. Conversely, the
room-temperature mechanochemical–hydrothermal
Fig. 6. (a) Average particle size (measured by DLS) of
stoichiometric HAp powders synthesized by the mechanochemi-
cal–hydrothermal technique as a function of dispersion medium.
Concentrations of SDBS and HTAB in their aqueous solutions were
2.0 and 1.0 mM, respectively. pH was adjusted by ammonium
hydroxide. Ethanol was used as a pure solvent. (b) A representative
particle size distribution of well-dispersed stoichiometric HAp
powder synthesized by the mechanochemical–hydrothermal tech-
nique at room temperature (dispersed in 1.0 mM HTAB aqueous
solution).
R.E. Riman et al. / Solid State Ionics 151 (2002) 393–402 401
technique allows precise control of HAp composition
while having a lower degree of control over particle
morphology and aggregation.
Acknowledgements
We gratefully acknowledge the research support by
National Institute of Health, Johnson and Johnson
Corporate Biomaterials Center and New Jersey Center
for Biomaterials. The authors wish to thank Yunda
Liu, Kevor S. TenHuisen, Victor F. Janas and Mamoru
Senna for fruitful discussion, Eric Gulliver for
obtaining FESEM images and Scott Atkinson for
providing carbonate analysis.
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