Plasticizing effect of water on poly(lactide-co-glycolide)
Introduction
Amorphous polymers are characterized by glass transition temperature (Tg), which is the transition point between a highly viscous brittle structure called glass and a less viscous, more mobile, rubbery state. The rubbery state (above the Tg), represents a liquid-like structure with high molecular mobility and is thus more prone to physical and chemical changes than the glassy state. The Tg value of a glassy polymer can be modified by blending with a small amount of a low molecular weight substance. Plasticization occurs when a small molecule, called a plasticizer, blended with a glassy polymer results in a decrease of the Tg of the polymer and its elastic modulus [1]. Such plasticization normally increases polymer flexibility or mobility. The reverse phenomenon, i.e. an increase in Tg, such as occurs with the addition of an agent, like a drug substance, has been defined as antiplasticization [2]. Therefore, the performance of a polymer can be modified in the presence of a plasticizer, or another substance, depending on the nature of the association between the various phases.
It has been shown that water molecules absorbed into a polymeric matrix act as an effective plasticizer, causing profound changes in the physicochemical properties of amorphous solids [3], [4]. Water, with a reported Tg of about − 135 °C [3], [4] can act as a very potent plasticizer. In fact, a blend of compatible amorphous materials can exhibit a single Tg that is intermediate to the Tgs of the pure components. Different theoretical equations are also available to predict the Tg of a two amorphous component mixture [3], [4]. Moreover, water may form stable bridges through hydrogen bonding resulting in an antiplasticizing effect [5].
Since the thermodynamic properties of the water sorbed into a polymer undergo change with respect to those of bulk water, the nature of the interaction between water and hydrophilic polymers has been investigated using calorimetric and spectroscopic techniques [6], [7]. Based on these studies, water has been classified into three “species”: (i) non-freezable bound water, (ii) freezable bound water, (iii) freezable free (bulk) water. Non-freezable bound water is defined as the water closely associated with the polymer matrix and does not give rise to observable phase transitions by calorimetric analysis. The freezable bound water is the fraction less closely associated to the matrix that does exhibit a melting/crystallization event remarkably different from that of bulk water. Freezable free (bulk) water shows the melting/crystallization temperature and the relative enthalpy not significantly different from that of bulk water [5], [6].
The behavior of water sorbed into polymers can be ascribed to different reasons, such as the effect of capillary condensation, the confinement of water by polymer structure, the formation of clusters, or the strong interactions between the highly dipolar water molecules and the polymer polar groups [8], [9], [10]. However, there has been rather limited attention given to the effect of water on hydrophobic polymers, especially polyorthoesters [11], [12], [13], [14].
The copolymers of lactic and glycolic acids (PLGA) are among the few polymers approved by the Food and Drug Administration for human clinical applications such as surgical sutures, implantable devices and drug delivery systems [15], [16], [17] because of their excellent biocompatibility, biodegradability and mechanical strength. Release of actives from drug delivery systems is controlled by a complex and not completely known mechanism including the diffusion through the polymer matrix and/or the fluid-filled pores and polymer degradation. In this regard, hydration represents the initial and, consequently, the fundamental step in the drug release process because the presence of water, in terms of biologic fluid or in vitro release media, is necessary for drug dissolution and diffusion through the drug delivery system. Additionally, it is essential for initiating and sustaining the hydrolytic degradation/erosion process of the polymeric matrix.
The aim of this work was to provide an understanding of the effect of water, bulk or vapor, on the Tg of poly(lactide-co-glycolide) in the early stage of hydration, prior to the onset of degradation. The physical state of water within the hydrated polymer and the effect of hygrothermal aging were investigated.
Section snippets
Materials
Poly(d,l-lactide-co-glycolide) (PLGA) RG503H (Mw 30,000 Da) was supplied by Boehringer Ingelheim (Ingelheim, Germany). Polyvinyl alcohol (PVA) (Mw 30,000–70,000 Da) was supplied by Sigma (Aldrich Chemical Company, USA). MgCl2, Mg(NO3)2, NaCl and KNO3 were provided by Fisher Scientific (USA). All the solvents were of analytical grade.
True density determination
The RG503H true density was determined using a helium pycnometer Ultrapycnometer 1000 (Quantachrome Instruments, USA). A 10 cm3 cell was used for the analysis and
Effect of bulk water on polymer Tg
When PLGA was incubated in bulk water for 1 h, the Tg was depressed from 45.5 to about 30 °C independent of the test temperature (Table 1). Surprisingly, after only 30 min of incubation at room temperature, the polymer was in a hydrated state because the Tg was already depressed to a similar value as obtained after 1 h of incubation (data not shown). Prolonging the incubation time until five days, no further changes were discernable, except in the case of the sample incubated at 55 °C since a
Conclusions
PLGA absorbed a small amount of water under high relative humidity and this water acted as a plasticizer lowering the Tg proportional to the amount of water in the matrix. Temperatures of incubation did not influence the plasticizing effect. The larger water content obtained during incubation in bulk water was ascribed to the presence of pure water domains, possibly clusters, which did not affect Tg and behaved as bulk water. It was concluded that water molecules absorbed at high relative
Acknowledgement
The authors would like to thank Professor Erik A. Grulke and Dr. Paul M. Bummer (University of Kentucky) and Dr. Stefano Giovagnoli (University of Perugia) for their helpful suggestions.
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