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Synergetic Role of Hypromellose and Methacrylic Acid Copolymer in the Dissolution Improvement of Amorphous Solid Dispersions.

Synergetic role of polymer blending on dissolution of amorphous solid dispersion was investigated. Dissolution rates of hypromellose (HPMC) and methacrylic acid copolymer (EUD) from the HPMC/EUD spray-dried sample (SPD) were improved compared to those of each single polymer SPD. Differential scanning calorimetry measurements revealed that the structural change in HPMC following heating was inhibited by co-spray-drying with EUD, suggesting an intermolecular interaction between the polymers. 13 C solid-state nuclear magnetic resonance (NMR) spectroscopy detected the change induced in the hydroxyl group of HPMC by co-spray-drying with EUD. Moreover, the carbonyl peak shape of EUD in the 13 C NMR spectra differed between EUD SPD and HPMC/EUD SPD, indicating that the dimer structure of the carboxylic acid of EUD was partially disrupted by the interaction with HPMC. An intermolecular interaction occurred between HPMC and EUD. The hydrogen bond reformation likely improved the dissolution rates of the polymers. The ternary griseofulvin (GRF)/HPMC/EUD SPD showed a significantly higher supersaturation level of GRF than the mixtures containing equal amounts of binary GRF/HPMC and GRF/EUD SPDs. The change of interaction mode between polymers improved the dissolution of solid dispersion. Therefore, polymer blending based on interpolymer interactions could be a practical strategy for designing excellent solid dispersion formulations.

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