Marcin Skotnicki1,2, Barbara Jadach1, Agnieszka Skotnicka1, Bartłomiej Milanowski1, Lidia Tajber2, Marek Pyda3,4, Jacek Kujawski5. 1. Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, 60-780 Poznan, Poland. 2. School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, College Green, 2 Dublin, Ireland. 3. Department of Biophysics, Poznan University of Medical Sciences, 60-780 Poznan, Poland. 4. Department of Chemistry, Rzeszow University of Technology, 35-959 Rzeszow, Poland. 5. Chair and Department of Organic Chemistry, Poznan University of Medical Sciences, 60-780 Poznan, Poland.
Abstract
The aim of this study was to characterize a 1:1 molar ratio of a pharmacologically relevant co-amorphous atorvastatin-irbesartan (ATR-IRB) system obtained by quench cooling of the crystalline ATR/IRB physical mixture for potential use in the fixed-dose combination therapy. The system was characterized by employing standard differential scanning calorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and intrinsic dissolution rate studies. Quantum mechanical calculations were performed to obtain information regarding intermolecular interactions in the studied co-amorphous ATR-IRB system. The co-amorphous formulation showed a significant improvement in the intrinsic dissolution rate (IDR) of IRB over pure crystalline as well as its amorphous counterpart. An unusual behavior was observed for ATR, as the IDR of ATR in the co-amorphous formulation was slightly lower than that of amorphous ATR alone. Short-term physical aging studies of up to 8 h proved that the ATR-IRB co-amorphous system remained in the amorphous form. Furthermore, no physical aging occurred in the co-amorphous system. FT-IR, density functional theory calculations, and analysis of T g value of co-amorphous system using the Couchman-Karasz equation revealed the presence of molecular interactions between APIs, which may contribute to the increased physical stability.
The aim of this study was to characterize a 1:1 molar ratio of a pharmacologically relevant co-amorphous n class="Chemical">atorvastatin-irbesartan (ATR-IRB) system obtained by quench cooling of the crystalline ATR/IRB physical mixture for potential use in the fixed-dose combination therapy. The system was characterized by employing standard differential scanning calorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and intrinsic dissolution rate studies. Quantum mechanical calculations were performed to obtain information regarding intermolecular interactions in the studied co-amorphous ATR-IRB system. The co-amorphous formulation showed a significant improvement in the intrinsic dissolution rate (IDR) of IRB over pure crystalline as well as its amorphous counterpart. An unusual behavior was observed for ATR, as the IDR of ATR in the co-amorphous formulation was slightly lower than that of amorphous ATR alone. Short-term physical aging studies of up to 8 h proved that the ATR-IRBco-amorphous system remained in the amorphous form. Furthermore, no physical aging occurred in the co-amorphous system. FT-IR, density functional theory calculations, and analysis of T g value of co-amorphous system using the Couchman-Karasz equation revealed the presence of molecular interactions between APIs, which may contribute to the increased physical stability.
Authors: Erin R Johnson; Shahar Keinan; Paula Mori-Sánchez; Julia Contreras-García; Aron J Cohen; Weitao Yang Journal: J Am Chem Soc Date: 2010-05-12 Impact factor: 15.419