Solid dispersions of the penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA): formulation design and optimization studies

Abstract

The penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA), which exists as an oily liquid, was incorporated into a solid dispersion for oral administration by the solvent evaporation method using blends of polyvinylpyrrolidone (PVP), Eudragit® RL PO and α-tocopherol. D-optimal mixture design was used to optimize the formulation. Formulations that had a high concentration of both Eudragit® RL PO and α-tocopherol exhibited low water absorption and enhanced stability of the DTPA prodrug. Physicochemical properties of the optimal formulation were evaluated using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). In vitro release of the prodrug was evaluated using the USP Type II apparatus dissolution method. DSC studies indicated that the matrix had an amorphous structure, while FTIR spectrometry showed that DTPA penta-ethyl ester and excipients did not react with each other during formation of the solid dispersion.. Dissolution testing showed that the optimized solid dispersion exhibited a prolonged release profile, which could potentially result in a sustained delivery of DTPA penta-ethyl to enhance bioavailability. In conclusion, DTPA penta-ethyl ester was successfully incorporated into a solid matrix with high drug loading and improved stability compared to prodrug alone.

Amorphous Solid Dispersions or Prodrugs: Complementary Strategies to Increase Drug Absorption

“…Another example of this approach 68 Eudragit® E100, or Eudragit® S100, 69 selfemulsifying solid dispersion of isradipine with poloxamer 407 which was formulated into hypromellose controlled-release tablet, 70 and penta-ethyl ester prodrug of diethylenetriamine pentaacetic acid with blends of polyvinylpyrrolidone (PVP), Eudragit® RL PO and a-tocopherol. 71 New polymers or new polymer combinations Improve stability or further tailor release kinetics and/or better maintain supersaturation with the goal to improve absorption or bioavailability…”