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Purpose Ethanol as an excipient is used to enhance the solubility of gemcitabine, but, sometimes, the dose of ethanol a patient may be given is much higher than the dose considered to be toxic. We aimed to assess ethanol-related symptoms and signs in patients receiving two formulations of gemcitabine, with and without ethanol. Methods A randomized double blind cross-over study was conducted. All patients being treated with gemcitabine received two consecutive doses of the drug, one diluted from a concentrate for solution for infusion (CSI) containing ethanol and the other from a lyophilized powder, without ethanol, which was used as control group. After each administration, patients were surveyed in order to assess the appearance of any alcohol consumption symptoms (dizziness, difficulty speaking, unsteady walking, impaired balance, mood swings and slower reactions). Widmark formula and the amount of alcohol measured on the breath (breathalyzer) were used to estimate blood alcohol concentration. Results Twenty-four patients received both formulations and were included in the analysis. Mean administered ethanol dose when prepared from CSI was 15.81 ± 2.25 g (mean ± SD). When using CSI gemcitabine, estimated blood ethanol concentration was 0.033 g/dl according to Widmark formula and 0.02 g/dl according to breathalyzer results. Although overall incidence of symptoms was higher in the study group, the difference was not statistically significant (33% vs. 25%; p = 0.53). Conclusions These findings prove there is no difference in the onset of ethanol related symptoms when using CSI instead of lyophilized powder on the reconstitution of gemcitabine.

The potential of ε-caprolactam (CAP) and trimellitic anhydride (TMA) compounds as novel chain extenders for poly(lactic acid) (PLA) has been assessed; the amounts of 0.01, 0.025, and 0.05 wt% each additive have been added. The chain extension was evidenced by the increase in PLA/CAP and PLA/TMA viscosities in mixing torque measurements and by infrared spectroscopy. PLA reaction with CAP and TMA has also been confirmed from contact angle and surface free energy studies, which have shown that the increase in TMA amount decreased the hydrophilicity of PLA due to the decreased concentration of terminal surface hydroxyl groups. However, the addition of CAP accentuated the PLA hydrophilicity as indicated by the increase in the polar component of the surface energy. On the other hand, the glass transition temperature of PLA/TMA and PLA/CAP decreased as a result of a local plasticizing effect, which favored the chain mobility and the crystallization of PLA due to the concomitant nucleating effect of the chain extenders moieties too. Furthermore, the higher molecular weight of PLA/CAP and PLA/TMA was responsible for their increased thermal stability and higher impact strength with respect to PLA. POLYM. ENG. SCI., 60:944-955, 2020.

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