Calcium Phosphate Bioceramics with Improved Properties: Chemical Synthesis

Kevin Thorne, Ph.D., Philippe D. Saint-Pierre, Ph.D. and Brad Hepler

University of Illinois at Chicago
Department of Restorative Dentistry
Division of Biomaterials and Technology
801 S. Paulina Street
Chicago, IL 60612-7212 USA

-
ABSTRACT As compared to metallic skeletal restorations,
calcium phosphate ceramics offer superior properties,
including: strong chemical resistance to environmental and
microbial corrosion, compositionally controllable in vivo
biological performance (bioactivity, solubility), high wear
resistances, and excellent mechanical properties.
Unfortunately, these ideal properties have not been obtained
because commercial calcium phosphate ceramics vary notably
in purity, crystal structure, and particle size.
As a novel processing solution, a two-step processing
technique was developed to result in a wide compositional
range of pure, stoichiometric calcium phosphates [xCaO*P,O,;
x=3.0-3.31. The first step involved the low temperature (SOC)
reaction between CaO and high purity phosphoric acid
[H,PO,, Na-2 ppb]. After eliminating soluble reactants and
impurity calcium phosphate phases by filtration with
deionized, distilled water, a crystalline calcium
orthophosphate [CaHPO,] powder was obtained in 61.1%
yields. The precipitate had an average particle size of 2.0 pn
with a homogeneous particle size distribution (1-14 pm).
Thermal analysis (TGA, DTA), x-ray diffraction (XRD) and
optical pyncnometry indicated that this product
endothermically transforms at 460°C [92.7% yield] into a
highly pure, crystalline calcium pyrophosphate (2CaO*P,O,)
with an average particle size of 3.3 pm (2-15 Fm).
In the second step, 2CaO*P,O, was intimately blended with
low alkali impurity CaCO, (lJ.3 mole%) and calcined in pure
oxygen atmospheres to result in controlled composition
calcium phosphate ceramics (xCaO*P,O,). To demonstrate the
potential of this technique, crystalline oxyapatite ceramics
(3.33Ca0*P20,) were obtained in high yields (85.8%) a t
temperatures exceeding 1000°C [lO"C/min., 50cdmin O,, 2hr]
with average crystalline particle sizes of 3.8 p (2-20~m).
Petrographic, refractive index characterization of the ceramic
precursor powders indicate that in all stages of processing,
high purity, spherical powders of uniform crystallinity and
particle size were obtained.
In contrast to conventional calcium phosphate ceramics, this
novel processing technique results in crystalline precursor
powders of high purity, controlled composition, uniform
crystal structure, and homogeneous particle size distribution.
These ceramic precursor powders can be used with
conventional ceramic processing techniques to result in
products with the improved properties required for clinical
success.
I. INTRODUCTION:
The anticipated lifetime of skeletal restorations is inadequate
due to a variety of material limitations, including: poor
adhesion to surrounding tissues, mechanical property
differences with natural tissues and poor wear resistance. The
subsequent medical procedures required for the repair or
replacement of failed restorations cause both patient trauma
and financial burden on the health care system. Since the
recipients of these restorations are increasingly younger and
more active persons, it is imperative that improved
technologies be developed to better satisfy the physical,
chemical, and biological requirements necessary for long-term
clinical success [ 11.
Currently, the preferred material for skeletal restorations are
metals because they satisfy the mechanical support
requirements of the body. Unfortunately, these materials often
fail due to stress shielding or metal allergies [2]. These
limitations have prompted efforts to design implants of
greater similarity to natural bone.
The use of calcium phosphate ceramics for skeletal
restorations can remedy the limitations of current materials.
Due to their compositional similarities with natural bone,
calcium phosphate ceramics offer improved biocompatibility
and "bioactivity" to reduce the problems of implant rejection,
and poor adhesion. Theoretically, the mechanical properties
(strength, elastic moduli) of fully sintered calcium phosphate
ceramics are very similar to natural bone. Therefore, their use
can eliminate stress shielding and subsequent peri-implant
osteoporosis which ultimately lead to weakened anchorage
and implant failure.
Unfortunately, these ideal properties have not been obtained
because commercial calcium phosphate ceramics vary notably
in purity, crystal structure, and particle size. As a novel
processing solution, a two-step processing technique was
developed to result in a wide compositional range of pure,
stoichiometric calcium phosphates [xCaO*P,O,; x=3.0-3.31.
In this paper, the synthetic technique is described and
characterized.
11. METHODS AND MATERIALS:
A two-step processing technique was developed to result in a
wide compositional range of pure, stoichiometric calcium
phosphates [xCaO*P,O,; x=3.0-3.31. The first step involved
the low temperature (25°C) reaction of freshly calcium oxide

0-7803-3869-3/97 10.0001997IEEE 260

 2CuO*P205+1.33CuC03 -3 33CuO*P,,O5+1.33C0,
Thermal analysis (TGA, DTA) reveal that reactants
endothermically transform at 760°C with a corresponding
weight loss of 14.5% [Figs. 4, 51. This initial reaction is
characteristic of calcium carbonate decomposition, according
to the following equation:
cuco, = Cu0+CO2(g)
This reaction mechanism is confirmed in the FTIR
spectroscopic results (Fig. 6 ) . After heat treatment at
temperatures exceeding 800°C, the characteristic carbonate
bonding vibrations at 1560 cm-' are eliminated. The remainder
Fig. 2. Thermai gravimetric analysis (TGA) of 2Ca0*P2O, preparation
of the spectrum is similar to that of C2P suggesting the
formation of a mixture of CaO and 2Ca0*P:2OS.Diffraction
1.74 0.40
peaks characteristic of crystalline CaO and C2P were
0.41
0.60
simultaneously observed in the XRD results (Fig. 7).
0.33

om 0.25 With further heat treatment, thermal analysis indicates that no

further weight losses occur. An endotheimic peak was
4aQ
.".....".."....."..
.*..(..+.*..l..Q..
.dr..<..J..O..C..Q..
o.,,
observed at 1160°C. At temperatures exceeding 110O0C, the
0.08

0.01
spectroscopic results simultaneously indicate the
-1.74
crystallization of (Fig. 6, 7). Particle size analysis measured
4.07
the average particle size to be 3.8 pm varying from 2-20 pm.
-l.M .o.t5
150 210 as0 a0 65a a60 m as0 (50 1cm 1150 $250
T~mperatunr C ] Although the infrared and x-ray diffraction studies indicate
Fig 3. Differential thermal analysis (DTA) of 2CaO-P,05 preparation the formation of the desired ceramic phases, these techniques
do not possess the resolution to detect presence of impurity
phases. It is extremely important that highly pure products be
lw.o
synthesized to optimize the mechanical property performance
of calcium phosphate ceramics. According to calcium
phosphate phase diagrams, oxyapatite compositions fall in a
E
binary phase region of tetracalcium phosphate [4CaO*P,O,]
-
U
and tricalcium phosphate [3CaO*P,0s]. The presence of
F
w.0
tricalcium crystal phases is devastating to the mechanical
property performance of calcium phosphate bioceramics as this
phase is water soluble.
6S.O
0 200 100 IW MO 1wa 1200 To detect the presence of impurity phases, optical petrography
Temperalure pC]
was used to identify impurity ceramic phases by determining
Fig. 4. Thermal gravimetric analysis (TGA) of 3.33CaO*P,05 preparation small lattice changes or perturbations through sensitive
refractive index measurements. Refractive index (RI) values
are measured on a petrographic microscope by matching
powder mounts to the RI of certified Shillaber oils (Cargille
Labs, Cedar Grove, NJ). Samples were illluminated with
sodium D line light to avoid color dispersion problems and
successively mounted in different RI oils until one is found
where the outlines of the particles can no longer be seen.
Using this simple technique, it was determined that in all
stages of processing, high purity, spherical powders of
.Y)- o
..
:
.;
.
;
.:
.:
.-
.
;
.:
.:
.;
.:
.:
.:
.;
.:
.:
.:
.~
.:
.
uniform crystallinity and particle size were obtained. The
1w Iw IW 700 m ltW tlm
Tempmlur. ['C] powders all exhibited uniform refractive indices characteristic
of the crystal structure described in the tlhermal reaction
Fig. 5. Differential thermal analysis (TGA) of 3.33Ca0*P2O,preparation
kinetics, [2CaO*P20,- 1.624, 3.33Ca0.P,0s- 1.6331

26 1
(CaO) [CaCo,, Na-Sppb, Aldrich] with high purity
phosphoric acid (H3P0,) [Albright & Wilson -Virginia,
Na-2ppbI. The calcium oxide was mixed into a [ lM] sucrosc
solution forming a calcium sucrate solution. This solution
was added incrementally to the phosphoric acid temperatures
below 5°C. With stoichiometrk P-aO addition, a white
precipitate was obtained at pH-3.95. After filtration cleaning
and drying, a pure calcium orthophosphate (CaHPO,) was
obtained in 61.1% yields. The powder was heated to 1000°C
(2hrs, 50 cc/min. 0,) to yield (92.7%) calcium pyrophosphate
(2CaO*P,O,). In the second step, the calcjum pyrophosphate
was intimately blended with low alkali impurity calcium
carbonate (CaCO,) and heated to temperatures exceeding
1000°C (50 d m i n . 0,) to produce calcium phosphate
ceramics of controlled composition. (xCaO*P,O,),.
Thermogravimehic (TGA) and differential thermal analysis
(DTA) were obtained using a TA Instruments thermal
analysis station [51 TGA, 1600 DTA]. Powdered samples
were respectively heated at 10"C/min to maximum
temperatures of 1200°C and 1600°C in pure 0, [50 cdmin.].
A controlled atmosphere (02, 99.998%) Carbolitea alumina
tube furnace was used to heat the products to various
temperatures (500°C- 1600°C) at a rate of 10"CYmin. Fourier
transform infrared analysis was performed [Perkin-Elmer
Paragon 10001 during thermal transformation by dispersing
powdered samples in KBr for analysis. X-ray diffraction
spectra were obtained using with a Siemens Diffraktometer
5000 at 0.40' 2Wmin. using CuKu.,radiation.
111. RESULTS AND DISCUSSION
Commercially available calcium phosphate compounds vary
notably in purity and stoichiometry. To obtain improved
products, a two-step method to prepare a wide compositional
range of pure, stoichiometric calcium phosphates was
developed. The first step involves the preparation of a
stoichiometric calcium pyrophosphate, [Ca,P,O,], according
to the following mechanism:
tMSucrmc(T<IoW tCuHP04 * x H ~ O
coo+~ ~ p+xH,o
o ,
~ C U H P Ox~H ~ O 'Iooc f CuO P 2 0 s + (I + x)H,O
9
To eliminate chemical impurities, it is essential that the initial
reactants be pure. To make a pure calcium sucrate solution, i t
is only necessary to add freshly calcined calcium oxide [ex:
CaCO,-+ CaO + CO2 (lOOO"C)] to a 1M sucrose solution.
Obtaining pure phosphoric acid is more difficult as
commercial USP grade precursors usually contain a
substantial quantity of sodium impurities. These impurities
are due to the fact that sodium chlorate is added to eliminate
carbon impurities from the natural "black acid" source.
Fortunately, developments in recent years have obviated the
"black acid" and a carbon and sodium free semi-conductor
grade is now available [Albright &Wilson - Virginia].
By gradually adding the chilled calcium sucrate solution to
dilute phosphoric acid (H,PO,), the reaction yields
stoichiometric calcium hydrogen phosphate dihydrate
(CaHPO,*xH,O) [CHPD] through the displacement of the
second hydrogen from the acid. In Fig. 1, the pH change was
observed as a function of CaO addition. With a slight
stoichiometric CaO addition, an insoluble white precipitate
was obtained at pH-3.95. By maintaining the reactant
solution at temperatures below 5"C, the precipitation of
impurity calcium phosphate phases was prevented. Under
these conditions, the reactants and their impurity products are
soluble. After filtration cleaning and drying (125"C),
spectroscopic and thermal evidence confirmed the production
of a pure, crystalline calcium orthophosphate
(CaHPO,, x=O.O) in 61.1% yields.
To obtain a pure, stoichiometric calcium pyrophosphate
(Ca,P,O,) [C2P], the washed and dried CHPD is simply
calcined at 900°C in air or oxygen. Thermal gravimetric
analysis (TGA) and differential thermal analysis (DTA)
reveal that CHPD endothermically transforms at 460°C with a
corresponding theoretical weight loss of 7.3% [Figs. 2, 31.
The DTA suggests the formation of pure C2P based on the
endothermic melting point at 1260°C. Field transmission
infrared spectroscopy (FTIR), x-ray diffraction (XRD) and
optical pyncnometry c o n f m that the product is crystalline,
high purity calcium pyrophosphate after pyrolysis at 1OOO"C.
Particle size analysis measured the average particle size to be
3.3 pm varying from 2-15 pm.
In the second processing step, the calcium pyrophosphate
[C2P] compound was reacted with controled compositions of
calcium carbonate [CaCO,] at high temperatures to result in
stoichiometric calcium phosphates [xCaO*P,O,]. To
demonstrate the potential of this technique, crystalline
oxyapatite ceramics (3.33Ca0*P205) prepared according to
the following equation:
CaO [Mole %]
Fig. 1. pH change during CaO addition to H,PO,
262
 l l 1lOO~C

1300°C

J ,
4WO
,
M O
,
3000
,
M O
,
2000 I500 IO00 0.. sa
Wavenumber [cm-I]
Fig. 6 . FTIR spectroscopic analysis during pyrolysis I.. e., - -1 . a.. .. E T .. 0. n, .
IV. CONCLUSIONS TWO - THETA [DEGREES ]
The novel processing technique results in crystalline calcium
X-ray diffraction analysis during pyrolysis
phosphate [xCaO*P,O,] ceramic powders of high purity,
controlled composition, uniform crystal structure, and
homogeneous particle size distribution. These ceramic
precursor powders can be used with conventional ceramic REFERENCES
processing techniques to result in products with the improved
properties required for clinical success. [ll Ducheyne, Bioceramics: Muteriul Charucteristics Versus In Vivo
Behavior. vol. 523, p.1. P. Ducheyne and J. Lemons, eds. Annals of
New York Academy of Sciences, New York, 1988.
ACKNOWLEDGMENTS
PI Brown and P. A. Ring, “Osteolytic Changes in the [Jpper Femoral
Shaft Following Porous Coated Hip Replacement,”J.Bone Joint Surg.,
The authors gratefully acknowledge the financial support of 67B,218, 1985.
the Whitaker Foundation, under contract Grant 5-2-085- 1.

263