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Role of Valsartan as an Antiplasticizer in Development of Therapeutically Viable Drug–Drug Coamorphous System

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journal contribution
posted on 02.03.2018, 00:00 by Anurag Lodagekar, Rahul B. Chavan, Naveen Chella, Nalini R. Shastri
In a rapidly growing field of coamorphous systems, selection of an appropriate coformer is a challenging task, especially while developing drug–drug coamorphous system, as one of the components should possess glass forming potential, and the combination generated is required to be therapeutically active. The present study was hence aimed toward exploring the glass forming potential of valsartan for the development of a therapeutically active drug–drug coamorphous system. A coamorphous system of valsartan–cilnidipine in six different weight ratios (4:1, 3:1, 2:1, 1:1, 1:2, and 1:3), along with the therapeutically relevant weight ratio (16:1) was prepared by quench cooling method and evaluated for antiplasticization effect of valsartan using differential scanning calorimetry (DSC)/modulated DSC. Generated coamorphous systems were studied for their dissolution benefits and stability under accelerated conditions (40 °C/75% RH). DSC and Fourier-transform infrared spectroscopy outcomes along with prediction of Tg of the drug–drug mixture using Gordon–Taylor and Couchman–Karasz equation demonstrated that, for the generation of the coamorphous system, antiplasticization activity of valsartan played a dominant role. A coamorphous system with higher valsartan content was found to provide significantly higher dissolution benefits and stability under accelerated conditions for 1 month. This study may pave the path for the development of a valsartan-based coamorphous system in the treatment of cardiovascular diseases.