Sacubitril Valsartan is a specialized cardiovascular pharmaceutical active substance belonging to the angiotensin receptor-neprilysin inhibitor (ARNI) class. It combines the pharmacological actions of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker. The pharmaceutical substance is commonly identified as Sacubitril Valsartan Sodium Hydrate or Sacubitril Valsartan Sodium Hemipentahydrate and is associated with CAS Number 936623-90-4 and the development code LCZ696. FDA substance records identify the material as Sacubitril Valsartan Sodium Hydrate, while regulatory documentation describes its characteristic sodium-containing salt complex with water of hydration.
Sacubitril Valsartan is designed as a combination pharmaceutical substance in which the two active components provide complementary mechanisms. Sacubitril is converted in the body to sacubitrilat, the active neprilysin-inhibiting metabolite. Neprilysin inhibition increases the availability of beneficial natriuretic peptides. Valsartan blocks the angiotensin II type-1 receptor and reduces the effects of angiotensin II. Together, these mechanisms help reduce cardiovascular strain and support the management of chronic heart failure.
The European Medicines Agency identifies sacubitril and valsartan as the active substances of Entresto and classifies the medicine under ATC code C09DX04. The medicine is authorized for treatment of symptomatic chronic heart failure with reduced left ventricular systolic function in adults and for specified paediatric heart-failure indications.
Sacubitril Valsartan Sodium Hydrate is a defined salt complex containing sacubitril, valsartan, sodium ions and water. A commonly used molecular representation is C48H55N6Na3O8·2.5H2O, corresponding to a molecular weight of approximately 958.01 g/mol. The anhydrous representation is C48H55N6Na3O8 with a molecular weight of approximately 912.97 g/mol. FDA GSRS records CAS 936623-90-4 and UNII WB8FT61183 for the hydrated substance.
The material is generally described as a fine white to practically white powder. Its salt-complex and hydrate characteristics make control of sodium content, water content and solid-state properties important during pharmaceutical manufacturing.
Sacubitril Valsartan is primarily associated with cardiovascular pharmaceutical manufacturing, particularly products intended for chronic heart failure management. The combination is used because sacubitril and valsartan act through complementary pathways affecting natriuretic-peptide signaling and the renin-angiotensin system.
The pharmaceutical substance is used in the manufacture of oral dosage forms, including film-coated tablets and granules. Current EMA product information identifies sacubitril/valsartan as the active substance combination and provides strengths expressed according to the individual sacubitril and valsartan components.
Quality control of Sacubitril Valsartan requires more than a conventional single-component API assay. Regulatory documentation describes testing for appearance, identity by IR/UV/XRPD, HPLC assay of the individual components and co-crystal/salt-complex material, sodium content, related substances, stereoisomers, residual solvents, water, heavy metals, calcium, chloride, microbial quality and particle size.
Chromatographic methods have also been developed for simultaneous determination of sacubitril and valsartan and for monitoring stereoisomers, degradation products and related impurities. Published stability-indicating methods demonstrate the importance of chromatographic separation and impurity control for this combination.
Sacubitril Valsartan manufacturing requires controlled stoichiometry, solid-state control, moisture management and validated analytical testing. Important quality attributes include assay of both active components, stereochemical purity, related substances, sodium content, water content, residual solvents and elemental impurities.
For pharmaceutical manufacturing and commercial API evaluation, appropriate documentation can include a Certificate of Analysis, specification sheet, analytical reports, HPLC chromatograms, residual-solvent data, safety documentation and technical information supporting quality and regulatory assessment.
Sacubitril Valsartan Sodium Hydrate should be protected from excessive moisture and contamination because its hydrated salt-complex structure makes water content an important quality attribute. Pharmaceutical-grade packaging should provide suitable protection from moisture and environmental exposure. Storage conditions should follow the validated stability data and approved product specification.
The finished medicinal product is also protected from moisture; current EMA product information instructs storage in the original package for moisture protection.
Typical documentation for Sacubitril Valsartan API can include Certificate of Analysis, product specification, batch analytical report, HPLC chromatograms, impurity profile, residual-solvent information, SDS, stability information and applicable regulatory or technical documentation.
Sacubitril Valsartan is an important modern cardiovascular pharmaceutical substance with a well-defined regulatory and analytical framework. Its combination of neprilysin inhibition and angiotensin-II receptor blockade makes it an important component of contemporary heart-failure therapy. Consistent control of assay, stereochemistry, related substances, sodium, water, residual solvents and solid-state characteristics is essential for reliable pharmaceutical manufacturing.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.1% |
| Heavy Metals | NMT 10 ppm |
| Water Content | 4.0–5.9% — |