The objective of this study was to assess the physicochemical effects of hydrating a hydrophobic end-capped poly(lactide-co-glycolide) (PLGA) polymer in the liquid and vapor state. PLGA RG503 polymer was incubated at 37°C in 0.5% polyvinyl alcohol (PVA) solution and at 90% RH. Samples were withdrawn at predetermined intervals and changes to polymer properties like glass transition temperature (Tg), moisture uptake, molecular weight change, and % acid number were determined using differential scanning calorimetry, Karl Fisher titrimetry, gel permeation chromatography, and acid base titrimetry, respectively. Study results showed that Tg was depressed instantaneously upon hydration, indicating that bulk water acted as a plasticizer of hydrophobic end-capped PLGA. Tg values decreased to levels below the incubation temperature when hydrated in 0.5% PVA solution but not in 90% RH. The drop in Tg exhibited a linear relationship ( ) to the amount of water uptake by the polymer; higher moisture uptake was noted with liquid water. Removal of moisture from the polymer matrix resulted in recovery of Tg, only up to a period of 14 days. Presence of water in liquid or vapor form caused a reduction in molecular weight of the polymer and a corresponding increase in % acid number over the duration of the study. 1. Introduction Hydrated polymer systems have been widely investigated owing to the effect of water on the performance of commercial polymers and the critical role played by water-polymer interactions in biological processes. In the presence of water, a polymer may exhibit changes in mechanical, chemical, rheological, and transport properties [1]. Depending on the chemical nature of the polymer, the presence of water may result in certain desirable or undesirable changes, causing a profound impact on the behavior of the polymer. Understandably, the manipulation of the rate and extent of moisture in a polymer has been the subject of much research, notably in the field of dosage form design and drug delivery [2–4]. Amongst other properties, amorphous polymers are often characterized by their glass transition temperature (Tg) that represents the point at which the solid glassy or highly viscous brittle polymer transitions into a less viscous, more mobile, rubbery state. In its solid glassy state, the polymer is practically immobile. Once in a rubbery state, the polymer chains become more flexible resulting in greater molecular mobility. With higher flexibility and molecular mobility at temperatures above the Tg, there is greater propensity for the polymer to undergo
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