Influence of processing and sterilisation on PCL Polymers, Rubber, Composites, 2003

Influence of processing and sterilisation on
properties of poly-e-caprolactone
N. A. Weir, F. J. Buchanan, J. F. Orr and D. F. Farrar
Poly-e-caprolactone (PCL) is a significant member of a group of polymers
regarded as bioabsorbable, having been the focus of extensive research for use
as a diffusion controlled drug delivery system. Degradation of PCL proceeds
through hydrolysis of the ester bonds in the polymer chains and is influenced
significantly by the polymer’s initial molecular weight and crystallinity. To
evaluate the effects of processing and sterilisation on these properties, PCL
pellets (CAPA 6400) were either injection moulded or extruded and sterilised
by ethylene oxide gas (EtO). Procedures were used to evaluate mechanical
properties, molecular weight and crystallinity. Upon processing and sterilisation
the molecular weights of the injection moulded and extruded materials did
not differ significantly from that of the PCL pellets, suggesting processing and
sterilisation did not initiate chain scission of the polymer’s ester bonds. However,
the crystallinity of PCL proved to be sensitive to injection moulding with an
increase of approximately 5% observed after processing, with sterilisation
by EtO gas causing annealing of the PCL pellets, injection moulded and
extruded material. After sterilisation the crystallinity of the PCL pellets
and extruded material increased by approximately 10% with a 4% increase
observed for the injection moulded material. The mechanical properties of
both the injection moulded and extruded material where not influenced by
sterilisation. The results from this investigation suggest that PCL’s molecular
weight is insensitive to processing and sterilisation. However, sterilisation by
EtO gas in the temperature range of 38–48°C used in this study does result
in annealing of the polymer. PRC/2034
© 2003 IoM Communications Ltd. Published by Maney for the Institute of
Materials, Minerals and Mining. Dr Weir (n.weir@qub.ac.uk), Dr Buchanan
and Professor Orr are in the School of Mechanical and Manufacturing
Engineering, Queen’s University Belfast, Ashby Building, Stranmillis Road,
Belfast, BT9 5AH, UK. Dr Farrar is at Smith & Nephew Group Research
Centre, York Science Park, Heslington, York, YO10 5DF, UK. Manuscript
received 23 May 2003. Accepted 25 August 2003.
INTRODUCTION is mainly due to their high level of biocompatibility,
acceptable degradation rates and versatility regardingPolymers have been employed in medical applications
physical and chemical properties 8. These polymersfor many years, first with the introduction of physio-
degrade in vivo by hydrolysis of their ester bonds. Duelogically inert biostable polymers, designed to retain
to this unstable nature they are sensitive to increasedtheir properties for years in vivo. Such materials have
temperature and exposure to moisture during pro-found applications in permanent joint prostheses.1
cessing and sterilisation.4,9 Some of the factors whichIn many cases only the temporary presence of a bio-
influence the absorption rate of these polymersmaterial is required, for support and to guide tissue
relate to their microstructural properties and includeregrowth. This has led to the development of bio-
chemical composition, molecular weight and degreeabsorbable polymeric materials, which are not physio-
of crystallinity.3,6logically inert, and will absorb over time, through the
Undoubtedly, three of the most significant membersnatural mechanisms of the human body.2 Synthetic
of the aliphatic polyester family are the poly(a-hydroxybioabsorbable polymers first came into commercial
acids), polyglycolide (PGA) and polylactide (PLA)medical use in 1970 with the introduction of a bio-
and the poly(v-hydroxy acid) poly-e-caprolactoneabsorbable suture material Dexon.3 Such polymers
(PCL)2,10 (Fig. 1). PCL is a semicrystalline polymer,have seen a steady progression in their development,
which melts in the range 59–64°C, depending onleading, in more recent years, to a growth in experi-
crystallite size, with a glass transition temperaturemental and clinical use in the field of orthopaedics
T
g
of −60°C,11 resulting in the polymer being in aand traumatology as fracture fixation devices, and in
rubbery state at room temperature. The crystallinitythe pharmaceutical industry as drug delivery devices.
of PCL tends to decrease with increasing molecularRecent advances have focused on developing bio-
weight.2 The crystallinity of PCL is reported to beabsorbable polymers as scaffolds in the field of tissue
engineering.4–7
Bioabsorbable polymers belonging to the aliphatic
polyester family currently represent the most attractive
group of polymers which meet the various medical and
1 PCL moleculephysical demands for safe clinical applications.8 This
Plastics, Rubber and Composites 2003 Vol. 32 No. 6 1DOI 10.1179/146580103225010264
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The Charlesworth Group, Huddersfield 01484 517077

2 Weir et al. Influence of processing and sterilisation on properties of poly-e-caprolactone
about 40% for molecular weights in excess of 100 000,
rising to 80% as the molecular weight decreases to
5000.11
PCL was initially evaluated for use as a bio-
degradable packaging material due to its ability to
be degraded by microorganisms,12–14 before it was
discovered that PCL could also be degraded by
hydrolysis under physiological conditions. PCL is
more hydrophobic and degrades much slower than
both PLA and PGA with the hydrolysis of PLLA,
an optical isomer of PLA, reported to be much faster
than that of PCL, even when the molecular weight of
PLLA was greater than that of PCL.14 While PLA
and PGA have found many applications in the field
2 Injection moulded test specimens: a tensile,of orthopaedics with various rods, screws, plates and
b flexural, c impactpins developed,15–17 orthopaedic applications for pure
PCL are rare owing to its long degradation time and
low strength.18,19 However, PCL has stimulated signi-
MATERIALS AND METHODSficant research into its potential use as a biomaterial,
mainly due to its good biocompatibility and exceptional Materials
ability to form compatible blends and copolymers with The polymer studied in this investigation, poly-e-
a wide range of other polymers, producing materials caprolactone (PCL) CAPA 6400, was manufactured
with unique elastomeric properties.20 For example, by Solvay Caprolactones and supplied by Brian Jones
the monofilament suture Monocryl.21,22 is reported and Associates (Hertford, UK) in pellet form. It was
to be the most pliable monofilament suture on the processed by injection moulding into ASTM standard
market. Significant research has also been focussed tensile, flexural and impact specimens and also by
on developing PCL for use as a long term diffusion extrusion into 2 mm diameter rod. The supplied poly-
controlled pharmaceutical drug delivery system due mer’s melting range was given as 58–60°C, glass
to its good permeability,8,11 reported to be 104 times transition temperature as −60°C and mean molecular
greater than pure poly-DL-lactide.23 Capronor, a one weight as 37 000. The crystallinity of the supplied
year implantable contraceptive delivery system based PCL was determined by DSC as approximately 40%.
on PCL is commercially available.11
Methods
Processing and sterilisation of PCL The material was injection moulded into ASTM
The degradation rate and mechanical properties of standard tensile, flexural and impact test specimens
aliphatic polyesters are known to be highly dependent (Fig. 2) on an Arburg Allrounder 320S 500–150
on a number of their material properties with crystal- machine, with the mould at approximately 25°C
linity, orientation, molecular weight and molecular (Table 1). Smaller tensile test specimens were then
weight distribution, the presence of impurities and prepared conforming to ASTM D 638–99 type V by
unreacted monomer all playing a significant role.3,24,25 cutting samples from the flexural test specimen using
Studies on both PGA and PLA have demonstrated a cutting die. These small tensile test specimens were
that processing and sterilisation can have a significant approximately 3 mm thick with an overall length of
effect on the polymers’ properties of crystallinity and 63·5 mm and a gauge length of 7·62 mm and were
molecular weight.26 Due to the unstable nature of used for characterisation of the injection moulded
PCL, properties critical to determining its degradation material. These small tensile test specimens were
profile may also be influenced by processing and manufactured and investigated in preparation for
sterilisation conditions. Generally, bioabsorbable poly- future long-term in vitro degradation studies.
mers are processed using conventional techniques Extrusion was conducted using a Killion KTS-100
suitable for all thermoplastics.4,9 The present work extruder with 25 mm screw (Table 1). The supplied
sets out to develop an understanding of how different PCL was extruded into lengths of 2 mm diameter rod
processes and sterilisation conditions will affect the and quenched in a water bath at 12°C (Fig. 3).
properties of PCL. Sterilisation was conducted by Griffith Microscience
This study investigates the processing of PCL by (Derbyshire, UK) on the standard ‘Cycle 33’ EtO
injection moulding and extrusion. It also quantifies cycle for medical polymers (Table 2).
the effects of sterilisation by EtO gas on mechanical
properties, crystallinity and molecular weight. Test
techniques utilised include tensile and shear testing for Table 1 Injection moulding and extrusion
mechanical strength, differential scanning calorimetry temperatures
(DSC) and gel permeation chromatography (GPC)
Injection moulding Extrusion
for investigating crystallinity and molecular weight
respectively. The aim is to develop processing con- Feed 30°C Zone 1 43°C
ditions that ensure consistent and predictable bio- Zone 2 50°C Zone 2 61°C
Zone 3 55°C Zone 3 65°Cabsorption behaviour, with future work aimed at
Zone 4 65°C Zone 4 65°Cdeveloping accelerated in vitro testing procedures
Nozzle 65°C Die 65°C
for PCL.
Plastics, Rubber and Composites 2003 Vol. 32 No. 6
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Weir et al. Influence of processing and sterilisation on properties of poly-e-caprolactone 3
3 Small tensile test specimen and extruded PCL
5 DSC thermograms of PCL in given forms
DSC curves was used to determine the material’s
melting point and enthalpy of fusion. The enthalpy
of fusion was then used to calculate the polymer’s
4 Shear test set-up crystallinity relative to a 100% crystalline sample
reported27 to be 139·5 J g−1. Three specimens were
tested at each condition.Tensile testing was conducted on the ASTM D
The weight and number average molecular weights638–99 type V tensile specimens using a JJ Lloyd EZ
of each sample were determined by GPC conducted50 testing machine, with 1 kN load cell and a cross-
by Rapra Technology Ltd (Shropshire, UK). Sampleshead speed of 100mmmin−1. Young’s modulus, tensile
were prepared by adding 10 mL of chloroform solventstrength and extension at maximum load were calcu-
to 20 mg of sample. A Plgel mixed bed columnlated from the load v extension curves. A minimum
with refractive index response detector was used. Theof five specimens was tested for each condition.
GPC system was calibrated with polystyrene and allShear tests were conducted on 30 mm lengths of
results are expressed as the ‘polystyrene equivalent’the 2 mm diameter extruded rod. The shear test
molecular weights. Each material sample was testedemployed was adapted from BS 2782 : Part 3 : Method
in duplicate.340B : 1978, ‘Determination of shear strength of sheet
material’ and was similar to the method used by
Suuronen et al.16 The PCL rod was slotted into a RESULTS AND DISCUSSION
hole aligned between two halves of a shear bracket
DSC(Fig. 4) and sheared simultaneously at both ends
under constant strain rate control. Testing was carried Before sterilisation
out using a Minimat materials testing machine at Figure 5 shows the DSC thermograms for the sup-
a strain rate of 1mm min−1. Five specimens were plied PCL pellets, injection moulded and extruded
tested for each condition. Shear strength (MPa) was material before sterilisation. A similar profile is
calculated as observed for each material with one distinct thermal
transition relating to the melting of the polymer’sF/2A=F/2pr2 . . . . . . . . . . . (1)
closely packed crystalline structure at approximately
where F is the load at maximum (N) and r the 63°C. The area under this peak was used to calculate
average specimen radius (mm). The overall shear the enthalpy of fusion and resulting crystallinity of
strength is divided by 2 in equation (1) to account the PCL pellets, injection moulded and extruded
for the double shearing action taking place. material as approximately 39%, 44% and 39%
The thermal properties of both the injection moulded respectively, relative to a 100% crystalline sample
and extruded PCL samples were analysed using (Table 3). It is evident that processing by extrusion
a Perkin Elmer DSC6 machine. Samples weighing did not significantly alter the crystallinity of PCL,
5–10 mg were heated at 10 K min−1 from −80°C to while a 5% increase in crystallinity is observed upon
80°C under nitrogen purge. The information from the injection moulding. With similar temperatures used
for each process (Table 1) this variation in crystallinity
Table 2 Ethylene oxide sterilisation conditions is attributed to the different cooling rates employed.
The extruded material was quenched in a water bathRelative
at approximately 12°C in comparison to the injectionConditions Temp, °C Time, h humidity, %
moulded material which was cooled in the mould at
Preconditioning 38–48 20–40 60–80 25°C and then subsequently in air, this slower cooling
Gas dwell chamber 36–46 7–7·5 NA rate providing the opportunity for a more crystalline
Degassing 38–48 16 NA
structure to develop. The reported glass transition
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7 Weight and number average molecular weights
of PCL in given forms
and extruded material increased by approximately
10% to 49% and by approximately 4% to 48% for
the injection moulded material. An increase in the
peak melting temperatures for each material of approxi-
mately 2 K was also observed (Table 3). The increases
in crystallinity and peak melting temperature after
sterilisation are attributed to annealing of the polymer
at the EtO sterilisation temperatures of between 38
and 48°C held for a duration of between 43 and 63·5 h
(Table 2), allowing further crystallisation, with a
possible increase in the crystallite size explaining the
increase in the peak melting temperatures.
Annealing of the polymer was confirmed as the
most probable reason for the increased crystallinity of
the sterilised PCL when comparing to PCL sterilised
by EtO on Griffith Microscience’s ‘Cycle 11’. Cycle 11
operated at the lower temperatures of 28–35°C and
for a significantly shorter period of between 5–9 h.
Results indicated no significant change in the profile
of the DSC thermograms or in the crystallinity or
peak melting temperature for both the extruded and
injection moulded material sterilised using Cycle 11,
confirming that the increased temperature used to
sterilise the PCL for this study on EtO Cycle 336 DSC thermograms of PCL before and after
was responsible for the increased crystallinity of thesterilisation: a pellets, b extruded, c injection
polymer.moulded
Molecular weight
of the supplied PCL pellets at −60°C is not visible
Figure 7 presents the change in molecular weight for
on the DSC thermograms, possibly due to its being
the PCL pellets through processing. It is evident that
masked by the material’s relatively high crystallinity.
neither injection moulding nor extrusion had a signi-
ficant effect on PCL’s weight average M
w
or numberAfter sterilisation
Sterilisation by EtO gas slightly altered each of the average M
n
molecular weights, with the supplied pellets,
injection moulded and extruded material having anmaterials’ DSC thermogram profiles. The onset of
the melting peak became more distinct with a slight M
w
of approximately 94 000 and an M
n
of approxi-
mately 61 000, giving a polydispersity (M
w
/M
n
) ofshift to higher temperatures also observed (Fig. 6),
evidence of an increase in the polymer’s crystallinity. 1·55. Figure 8 shows the molecular weight distri-
butions, with the PCL pellets, injection moulded andAfter sterilisation the crystallinity of the PCL pellets
Table 3 Thermal properties of PCL before and after sterilisation
Before EtO sterilisation After EtO sterilisation
Melting Enthalpy of Crystallinity, Melting Enthalpy of Crystallinity,
Material point, °C fusion, J g−1 % point, °C fusion, J g−1 %
Pellets 63·4 54·9 39·4 64·7 68·5 49·1
Injection moulded 63·2 61·4 44·0 65·1 66·9 47·9
Extruded 63·2 54·2 38·9 65·2 67·8 48·6
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Weir et al. Influence of processing and sterilisation on properties of poly-e-caprolactone 5
8 Molecular weight distributions of PCL in given
forms
10 Tensile test curve for large injection mouldedextruded materials distributions being superimposed
PCL specimens
on top of each other, confirming processing did not
alter PCL’s molecular weight. Sterilisation also had
no significant effect on the materials molecular weight.
ductile polymer, with testing conducted at room tem-
perature well above its glass transition temperature
of −60°C. Considering each region labelled on Fig. 9:
Mechanical properties (i) first, an initial peak appears, associated with
the formation of a neck, followed by a plateauTensile testing of injection moulded PCL
of constant force as more material is drawnIt is evident from Figure 9 that the injection moulded
into the neck from the sample’s gauge lengthPCL exhibits a unique tensile behaviour, initially
(ii) the force then gradually begins to increase.behaving like a typical viscoelastic polymer up to the
With PCL being very ductile, necking is notyield point s
y
followed by solid state deformation as
simply confined to the short gauge length,the molecular chains align.28 The load then increases
even at the high strain rate of 100 mm min−1.slightly before a sharp drop is noted followed by a
Rather, necking reaches the wide end of thedistinctive period where the load oscillates. Finally,
dumbbell (generally the top end first) andthere is a constant increase in load followed by a
material starts to get drawn from there, withsmall plateau before failure. The oscillating load
its greater cross-sectional area resulting inbehaviour is even more evident on the large tensile
an increased load required to maintain thespecimens tested at 50mm min−1 (Fig. 10). The picture
constant strain rateshows a close-up of a large PCL tensile sample in
(iii) a sharp drop in load is then noted as materialthe region of the oscillating load behaviour. Equally
begins to draw from the lower end of the neck,spaced ridges can clearly be seen across the width
resulting in a plateau as the necking continues;of the sample. This behaviour is very visible during
generally at this point the distinctive oscillatingthe test and consistent between samples prepared in
behaviour is observed.different injection moulding batches. It is speculated
(iv) finally, again, there is an increase in load asthat the material must be undergoing some sort of
necking grows into the wide end of the lowerstrain hardening effect, at stress concentrations associ-
end of the dumbbell, followed soon after byated with the reduction in section, apparent in some
failure.metals, as a localised area of the polymer strain
A similar profile is also observed for the sterilisedhardens before releasing, followed by subsequent
injection moulded PCL. Table 4 presents the data forlocalised areas up until failure.
the tensile tests conducted on PCL before and afterThe tensile behaviour of the small specimens can
sterilisation, indicating that although the crystallinitybe explained considering the geometry of the dumb-
of the sterilised material increased by approximatelybell sample under test and the fact that PCL is a very
4% this had no significant effect on PCL’s tensile
properties with a Young’s modulus of 90 MPa and a
tensile strength of 21 MPa observed both before and
after sterilisation.
Table 4 Tensile properties of injection moulded
PCL
Before After
Property sterilisation sterilisation
Young’s modulus, MPa 90·85 90·80
Tensile strength, MPa 21·31 21·329 Tensile test curve for small injection moulded
Extension at maximum load, mm 3·74 3·75
PCL specimens
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26. . . , . . , . . , . 
ACKNOWLEDGEMENTS and . . : Proc. 17th European Conf. on
The authors would like to thank Brian Jones and ‘Biomaterials’, Barcelona, Spain, Paper L7. 2
Associates for supplying the PCL, Griffith Microscience 27. . , . , .  and . :
for the ethylene oxide sterilisation and Rapra Tech- Eur. Polymer J., 1972, 8, 449–463.
nology Ltd for the molecular weight characterisation. 28. . . . ‘Plastics Engineering’, 3rd edn, 18;
1998, London, Butterworth Heinemann.And finally, EPSRC for financial assistance.
prc0002034 09-10-03 10:29:48 Rev 14.05

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Influence of processing and sterilisation on PCL Polymers, Rubber, Composites, 2003

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