Solution synthesis of hydroxyapatite designer particulates

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-


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 +


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).


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.


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.


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).


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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Solution synthesis of hydroxyapatite designer particulates