The impact of triethyl citrate leaching from HPMC-phthalate based isolated films on film permeability and thermal properties

Abstract

The primary objective of this study was to investigate to what extent triethyl citrate (TEC), a commonly used plasticizer, was leached from hydroxypropyl methylcellulose phthalate (HPMC-P)-based isolated films and how this affects the permeability of the film for the model drug acetaminophen. The effect of the plasticizer on the glass transition temperature (Tg) of HPMC-P films was studied using modulated differential scanning calorimetry (mDSC) and utilized to estimate the extent of plasticizer leaching. A linear relationship between the Tg of the film and the weight proportion of the plasticizer was established and applied to develop a calibration curve, which enabled the quantification of plasticizer leaching from the isolated films. The leaching profiles of the plasticizer obtained from mDSC analysis demonstrated a slow migration from the film, 10 % w/w TEC films took nearly 24 h to completely leach out the plasticizer (95.1 ± 10.6 %) from the film, whereas 20 % w/w TEC films had leached out 76.7 ± 12.64 % of plasticizer within the similar exposure time. A concentration-dependent, slow leaching of plasticizer was observed, where films with a higher plasticizer content exhibited a reduced rate of leaching. This finding was consistent with the observed percentage of mass loss and the medium uptake capacity study of the films. Moreover, the addition of plasticizer at a concentration of 10 % w/w provided a permeability coefficient of 1.35 ± 0.19 e-06 (cm/s), while 20 % w/w yielded a coefficient of 1.97 ± 0.40 e-06 (cm/s), which directly contributed to an increase in the film’s permeability compared to the films without plasticizer (1.19 ± 0.11 e-06 cm/s).