Effect of hydrolytic degradation on themicrostructure of quenched, amorphouspoly(glycolic acid): an X-ray scattering studyof hydrated samplesElizabeth King,1 Susan Robinson2 and Ruth E Cameron2*1Pfizer Ltd, Sandwich, Kent, UK2University of Cambridge, Department of Materials Science and Metallurgy, New Museums Site, Pembroke Street, Cambridge, CB2 3QZ,UK

Abstract: The effect of hydrolytic degradation on the microstructure of unoriented, quenched

poly(glycolic acid) (PGA) was investigated using simultaneous small- and wide-angle X-ray scattering

(SAXS/WAXS). Samples were analysed immediately after removal from the degradation media in

order to prevent dehydration. Analysis showed that the material initially contained a small degree of

crystallinity. On degradation, the material rapidly crystallized, developing a broadly similar

morphology to samples crystallized from the melt. The behaviour of these new structures on

degradation was similar to that observed in the precrystallized samples previously reported. The

crystal density remained constant and little change was seen in the lateral extent of the crystal lamellae.

Both the crystallinity and SAXS scattering power (or invariant) increased during the ®rst 30 days

which may be due to the preferential removal of amorphous material and further crystallization of

amorphous chains. The crystallization of amorphous material was facilitated by plasticization due to

the ingress of water and the cleavage of amorphous chains.

In both quenched and precrystallized material, the average lamellar spacing fell and then rose

during degradation. It is not possible to interpret this unambiguously from the SAXS data alone. It

may be partially the consequence of a two-stage removal of amorphous material. Alternatively, the

behaviour may be explained by changes in the osmotic potential of the amorphous layer on

degradation, together with insertion crystallization.

# 1999 Society of Chemical Industry

Keywords: hydrolytic degradation; poly(glycolic acid); plasticisation; crystallinity; small-angle X-ray scattering;wide-angle X-ray scattering

INTRODUCTIONPoly(glycolic acid) (PGA) is a biodegradable polymer

with good biocompatibility and physiologically toler-

able degradation products. It is currently used as a

synthetic material for absorbable sutures, bone-®xa-

tion devices and dental devices.1 PGA is the simplest

aliphatic polyester and is an ideal model polymer to

study the process of degradation of this class of

polymers.

PGA is degraded in the body ¯uids by bulk

hydrolysis of the hydrophilic ester bonds.2,3 In a

previous paper, we reported the effects of hydrolytic

degradation on the microstructure of unoriented,

semicrystalline PGA.4 The samples were studied

immediately after removal from the degradation media

to prevent microstructural damage caused by the

dehydration process5 and information was obtained

from simultaneous small- and wide-angle X-ray

scattering (SAXS/WAXS) and ultraviolet spectro-

photometry (UV) experiments of the partially de-

graded structures.

Following on from the previous work, this paper

considers the effect of changing the initial microstruc-

ture of PGA on the progress of hydrolytic degradation.

Samples were prepared by quenching PGA from the

melt, and the effects of degradation on the micro-

structure were observed using SAXS/WAXS.

The work presented in this paper gives microstruc-

tural information of importance in the prediction and

control of mechanical properties during hydrolytic

degradation of polymers. It also aids the understand-

ing of the diffusion of molecules through degrading

polymers and on how to control the rate of their

release.

Polymer International Polym Int 48:915±920 (1999)

* Correspondence to: Ruth E Cameron, University of Cambridge, Department of Materials Science and Metallurgy, New Museums Site,Pembroke Street, Cambridge, CB2 3QZ, UKContract/grant sponsor: EPSRCContract/grant sponsor: Pfizer Ltd(Received 26 November 1998; revised version received 6 April 1999; accepted 1 June 1999)

# 1999 Society of Chemical Industry. Polym Int 0959±8103/99/$17.50 915

EXPERIMENTALMaterialsPellets of PGA, with an inherent viscosity of 1.33dl

gÿ1, were obtained from Medisorb Technologies,

Cincinnati, Ohio, USA. Plates 1cm�4cm were

formed by melting 0.8g PGA at 230°C in a copper

mould with a polytetra¯uoro-ethylene (PTFE)-coated

aluminium base, then quenching in iced water until

cooled. Precrystallized samples were not quenched

into iced water, but held at 160°C for 5min to allow

crystal structures to form. Phosphate-buffered saline

solution, pH 7.4, from Sigma-Aldrich Co, Dorset,

UK, was made up with distilled water and with 1%

penicillin-streptomycin antibiotic solution, from

Sigma-Aldrich Co. All apparatus was autoclaved for

30min before use.

Small and wide angle X-ray scatteringPlates of PGA were degraded in 50ml of buffer

solution at 37°C. After predetermined periods of time

the plates were removed and immediately analysed by

SAXS/WAXS at the SRS Laboratory, beam line 8.2, at

Daresbury, UK. Short exposure times were possible

due to the high intensity of the synchrotron radiation.

This eliminated any problems arising from changes to

the sample during the exposure. Ryan et al6 have

described the experimental technique of SAXS/WAXS

used to determine polymer structure.

Data were collected on a quadrant SAXS detector

located 3.5m from the sample, and a position-sensitive

curved knife-edge WAXS detector. The WAXS and

SAXS detectors were calibrated using high-density

polyethylene and wet rat-tail collagen, respectively.

The samples were placed directly into the beam and

exposed for 30s. The data were corrected for back-

ground scattering by subtracting the scattering from a

straight-through beam, and for sample thickness and

transmission by dividing by the signal from an

ionization chamber directly behind the sample.

It was not possible to monitor the change in

molecular weight of the polymer during degradation

owing to a lack of suitable solvent for analysis.

RESULTSSAXS resultsFigure 1 shows the SAXS data obtained for the

quenched samples. In the sample degraded for 1h a

small lamellar peak is visible. This implies that the

quenching of the samples did not produce completely

amorphous samples and that some degree of crystal-

linity is present in the starting material. The small

lamellar peak slowly increases in intensity with

degradation. At later stages of degradation, the

intensity of the scattering at very low angles increases.

This additional scattering may be due to the formation

of large water-®lled voids or to a very broad distribu-

tion of lamellar crystals.

An estimate of the average lamellar spacing for each

structure was calculated by application of the Bragg

equation to Lorentz-corrected peak positions. The

Lorentz correction is applied by multiplying the

intensity by the square of the scattering vector, thereby

converting the data from randomly oriented lamellar

stacks to that from a single lamellar stack. These

average lamellar spacings are shown in Fig 2. Initially,

the quenched PGA had an average lamellar spacing of

88AÊ . This is approximately 7AÊ lower than that

previously observed in PGA that had been precrys-

tallized at 100°C and 160°C.4 On degradation, the

average lamellar spacing falls over the ®rst 2±3 weeks

and then rises a little. This behaviour is very similar to

that observed for the precrystallized material, although

the average lamellar spacings were generally smaller.

The scattering power or invariant of a SAXS pro®le7

Q can be calculated using eqn (1). This term is

unaffected by the shape of the scattering entities but is

dependent on the change in electron-density differ-

ences within the structure.8

Q � 1

2�2

Z10

q2Idq �1�

The calculated invariant is shown in Fig 3. The

Figure 1. SAXS intensity profiles for quenched samples after variousstages of degradation. The samples are observed without the removal ofbuffer solution. The peak intensity increases and the position shifts asdegradation proceeds.

Figure 2. Average lamellar spacing plotted against degradation time forquenched samples. The values are obtained by applying the Braggequation to the peak position of the Lorentz-corrected SAXS intensityprofiles.

916 Polym Int 48:915±920 (1999)

E King, S Robinson, RE Cameron

integration was performed within the limits of the data

collection. Because the intensities are in arbitrary

units, the values will differ from the true value by a

constant factor k. On degradation, the invariant

increased.

WAXS resultsFigure 4 shows the WAXS data obtained from

quenched samples after various stages of degradation.

The sample degraded for 1h shows signs of the (110)

and (020) crystalline peaks associated with PGA;

however, the amorphous halo is much larger than that

observed for the samples crystallized from the melt.4

During degradation, the crystalline peaks rapidly

develop.

WAXS pro®les were analysed by ®tting a Gaussian

function to the crystalline peaks and a third-order

polynomial to the amorphous halo. The positions of

the (110) and (020) peaks were used to calculate the

dimensions of the unit cell. Figures 5 and 6 show that

no major changes occurred to the unit cell or crystal

density with degradation. Furthermore, no major

changes occurred to the widths of the peaks (Fig 7).

The degree of crystallinity at each stage of degrada-

tion was determined from the ratio of the area under

the crystalline peaks to the total area under the WAXS

Figure 3. The invariant Q from the SAXS intensity profile, plotted againstdegradation time. Since the intensity is given in arbitrary units, the invariantis also obtained in arbitrary units, related to the standard units by anunknown constant k.

Figure 4. WAXS intensity profiles for quenched samples after variousstages of degradation. The samples are observed without removal of buffersolution.

Figure 5. Unit cell parameters plotted against degradation time forquenched samples. Parameters in the a direction are denoted by circles, inthe b direction by squares, and in the c direction by diamonds.

Figure 6. Crystal density plotted against degradation time for quenchedsamples. These values were calculated from the orthorhombic unit cellparameters shown in Fig 5.

Figure 7. Width of the WAXS peaks plotted against degradation time forquenched samples. Widths of the (110) peak are given by circles andwidths of the (020) peak by squares.

Polym Int 48:915±920 (1999) 917

Hydrolytic degradation of PGA

pattern. An increase in crystallinity was observed over

the ®rst 4 weeks (Fig 8). The values observed are lower

than might be expected, and absolute values should be

treated with caution.

Table 1 presents a comparison between parameters

obtained from the quenched samples and the samples

precrystallized at 160°C.

DISCUSSIONChanges in the crystalline phaseThe quenched sample degraded for 1h exhibited a

fractional crystallinity of approximately 0.03 (Fig 8).

This degree of crystallinity is thought to be present in

the starting material and not to be due to the effects of

hydrolytic degradation. The unit cell parameters (Fig

5) found from the developed crystalline structure were

in reasonable agreement with those reported by

Chatani et al9 (a =5.22AÊ , b =6.19AÊ , c =7.02AÊ ). As

was observed in the precrystallized structures,4 the

effect of degradation on the unit cell parameters and

the crystal density is small.

The degree of crystallinity increases rapidly over the

®rst 4 weeks, from approximately 0.03 after 1h

degradation to 0.20 after 28 days (Fig 8). Two factors

can contribute to the rise in crystallinity. Firstly, the

preferential removal of amorphous material during

degradation will mean than the crystallinity of the

remaining material rises. Secondly, the lowering of

molecular weight on degradation and the plasticizing

effect of water will favour crystallization of amorphous

material. The plasticizing effect of water is illustrated

by the glass transition temperature of PGA found by

DSC. Dry PGA has a glass transition temperature of

41�2°C which falls to 31�2°C and levels off over the

®rst few hours of hydration at 37°C.10 Hydration thus

moves the material into the regime above its glass

transition, facilitating crystallization. It is interesting to

note that if the samples are held at 37°C without

hydration, there is no analogous change, so the effects

are not driven by the increased temperature alone.10

The low initial value of crystallinity in the quenched

material means that crystallization rather than removal

of the amorphous phase must be, at least in part,

responsible for the increased crystallinity in these

samples. Crystallization is also likely to play a role

during degradation of the precrystallized material.

Simple measurement of the crystallinity alone, how-

ever, cannot determine the relative importance of

these two mechanisms.

Overall, the maximum level of crystallinity

measured (0.20) was lower than the value of 0.50

seen in the samples precrystallized from the melt.4

This is to be expected because the precrystallized

material formed many of its crystals at 160°C. While

both materials are likely to crystallize during the

degradation at 37°C, at this temperature crystal

growth is less favoured, chain-scission and plasticiza-

tion notwithstanding. This means that the quenched

material reached a lower overall value.

During degradation, the widths of the WAXS peaks

were largely unchanged (Fig 7). The peak widths were

greater for the quenched material (0.59° for (110)

peak) than the samples precrystallized from the melt

(0.52° for (110) peak) (see Table 1). This was again

due to the lower crystallization temperature of the

quenched material resulting in structures with smaller

or less ordered crystals.11,12 Overall, the changes to the

unit cell and to the lateral extent of the crystals were

very small during the period of degradation studied.

As degradation continued over the ®rst 30 days, the

crystallinity continued to increase together with the

invariant (Figs 3 and 8). After this period both these

terms levelled off. The increase in the invariant is

Figure 8. Crystallinity of the samples calculated from the WAXS intensityprofiles versus degradation time.

Table 1. Comparison between parametersobtained experimentally from the quenchedsamples and samples precrystallized at 160°Cduring in vitro degradation

Parameter Quenched Crystallized at 160°C

Initial lamellar spacing (AÊ ) 87 94

Minimum lamellar spacing (AÊ ) 64 72

Time at which minimum spacing (days) 21 21

Lamellar spacing after 63 days degradation (AÊ ) 70 84

Initial fractional crystallinity 0.03 0.35

Crystallinity after 63 days' degradation 0.18 0.49

Time at which maximum crystallinity occurs (days) 28 42

Average WAXS (110) peak width (deg) 0.59 0.52

Average WAXS (020) peak width (deg) 0.94 0.74

Average crystal density (gcmÿ3) 1.73 1.74

918 Polym Int 48:915±920 (1999)

E King, S Robinson, RE Cameron

dif®cult to interpret, because it is dependent on several

changing parameters. It is likely to be dominated by an

increase in electron-density difference between crys-

talline and amorphous phases when amorphous

material is replaced by buffer solution. However, the

invariant will also change with changing crystallinity,

crystal surface-to-volume ratio, and crystal-interface

thickness. Any water-®lled voids created will also

contribute.

Changes to the lamellar structureThe lamellar structure observed after 1h degradation

(Fig 1) gave a scattering pattern which showed a small

broad peak. The value of 87AÊ was approximately 7AÊ

lower than that of 94AÊ reported for the PGA samples

crystallized from the melt.4 This difference is to be

expected, the lower temperature of crystallization

resulting in a ®ner lamellar structure.

Over the ®rst 3 weeks of degradation, the average

lamellar spacing dropped (Fig 2). This coincided with

the main increase in crystallinity (Fig 8) and invariant

(Fig 3). After 3 weeks, the average lamellar spacing

rose again. A similar pattern was observed in the

behaviour of the lamellae of precrystallized material.4

The minimum in the curve was observed at about the

same time of degradation. However, the increase in

average lamellar spacing at later stages of degradation

was greater in the precrystallized structures.

The behaviour of the average lamellar spacing

cannot unambiguously be explained with the data

presented here. There are three physical mechanisms

which may affect it in both quenched and precrystal-

lized samples.

The ®rst possible mechanism controlling the aver-

age lamellar spacing concerns the fact that the loss of

amorphous material may occur via a two-stage mech-

anism. The tie chains in the amorphous layers will

exhibit a range of conformations from highly coiled

(Gaussian) to more tight (linear). In the ®rst stage,

reactive, highly-coiled chains are degraded, allowing

tight tie chains to relax to more entropically favourable

conformations. This relaxation pulls the crystals closer

together and creates stresses elsewhere in the struc-

tures. The newly coiled tie chains are now progres-

sively degraded, partially releasing the crystals and

allowing the lamellar structure to expand. This mech-

anism requires that coiled chains be more reactive than

extended ones and would result in signi®cant mass loss

of the sample in the early stages of degradation.

The increase in average lamellar spacing in

quenched samples is smaller than that reported for

PGA samples crystallized from the melt.4 Since the

crystals in the quenched samples mostly form during

the degradation step, the internal strain arising from

degradation is likely to be lower than in the pre-

crystallized samples, and this could give less driving

force for expansion.

The second possible mechanism concerns crystal-

lization of amorphous material. This would be

facilitated by an increase in mobility resulting from

both the plasticizing effect of the in®ltrating water and

the cleavage of amorphous chains.2,13 (In this case, no

distinction is made between amorphous material of

different conformations.) If a new crystal is inserted

between two primary lamellae, the average lamellar

spacing in that area of the sample falls by a factor of

about two. Thus the average lamellar spacing of the

whole sample can be signi®cantly reduced by the

insertion of new crystal lamellae between some

existing lamellae. This mechanism does not require

signi®cant mass loss in the early stage of degradation.

The third mechanism takes into account the fact

that the osmotic potential of the amorphous layers

changes as degradation proceeds. This changes the

af®nity for water and the structure swells or contracts

accordingly. (Although, in theory, this should be

reversible and hence the hypothesis testable by

removing water, in practice the partially degraded

structure undergoes large-scale distortion on dehydra-

tion and the test is not useful for this purpose.5) Since

the chemical groups formed on degradation are likely

to make the structure more hydrophilic, this mechan-

ism is most useful for explaining the rise in the average

lamellar spacing at long degradation times rather than

the fall at short times. Thus, the fall and rise in the

average lamellar spacing could be explained by a

combination of insertion secondary crystallization and

changes in osmotic potential of the amorphous layers.

The results presented here cannot distinguish

between these mechanisms. Further experiments are

underway.

CONCLUSIONSThe quenched material had a small degree of crystal-

linity that rapidly increased during degradation,

facilitated by hydrolytic attack and water plasticiza-

tion. This structure is broadly similar (although more

disordered) than that observed in structures precrys-

tallized from the melt. It exhibited a similar behaviour

on further degradation. The crystal density remained

constant and little change was seen in the lateral extent

of the crystal lamellae.

The fall and rise in the average lamellar spacing may

be interpreted as re¯ecting a two-stage loss of amor-

phous material. Alternatively, a mechanism involving

insertion crystallization and changes in the osmotic

potential of the amorphous layers may be responsible.

ACKNOWLEDGEMENTSThis work was funded by an EPSRC studentship with

CASE sponsorship from P®zer. The X-ray experi-

ments were performed on station 8.2 of the CCLRC

Daresbury Laboratory with the advice and assistance

of Dr BU Komanscheck. Software from the CCP13

suite was used in the analysis.

Polym Int 48:915±920 (1999) 919

Hydrolytic degradation of PGA

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E King, S Robinson, RE Cameron