Novel crystal forms of Entresto: a supramolecular complex of trisodium sacubitril/valsartan hemi-pentahydrate

Shaikh, Tabrez Rafique; George, Christy; Bhukya, Priyanka; Shelke, Nikita; Pawar, Komal Ishwar; Garai, A.; Dandela, Rambabu; Gonnade, Rajesh G.; Nangia, Ashwini

doi:10.1039/d2ce01009g

Cited by 3 publications

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References 24 publications

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“…Usually, therapeutic cocrystals consist of two components, an API and a complementary molecular coformer, although API:API cocrystals are also known [22,23]. For example, this group includes Entresto ® , a cocrystal of the drugs valsartan and sacubitril used to treat heart failure [24]. The basic requirement for a suitable coformer is to be pharmaceutically acceptable, i.e., generally regarded as safe (GRAS) substances [25].…”

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confidence: 99%

Amorphization of Ethenzamide and Ethenzamide Cocrystals—A Case Study of Single and Binary Systems Forming Low-Melting Eutectic Phases Loaded on/in Silica Gel

et al. 2023

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The applicability of different solvent-free approaches leading to the amorphization of active pharmaceutical ingredients (APIs) was tested. Ethenzamide (ET), an analgesic and anti-inflammatory drug, and two ethenzamide cocrystals with glutaric acid (GLU) and ethyl malonic acid (EMA) as coformers were used as pharmaceutical models. Calcinated and thermally untreated silica gel was applied as an amorphous reagent. Three methods were used to prepare the samples: manual physical mixing, melting, and grinding in a ball mill. The ET:GLU and ET:EMA cocrystals forming low-melting eutectic phases were selected as the best candidates for testing amorphization by thermal treatment. The progress and degree of amorphousness were determined using instrumental techniques: solid-state NMR spectroscopy, powder X-ray diffraction, and differential scanning calorimetry. In each case, the API amorphization was complete and the process was irreversible. A comparative analysis of the dissolution profiles showed that the dissolution kinetics for each sample are significantly different. The nature and mechanism of this distinction are discussed.

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