Zofenopril Calcium is a pharmaceutical active ingredient belonging to the angiotensin-converting enzyme (ACE) inhibitor class. It is the calcium salt of zofenopril and is used in pharmaceutical formulations for the management of hypertension and selected cardiovascular conditions. Zofenopril itself is a prodrug that is converted in the body to the active metabolite zofenoprilat, which inhibits angiotensin-converting enzyme and reduces the formation of angiotensin II.
Zofenopril Calcium is chemically identified as the calcium salt of zofenopril. FDA Global Substance Registration System identifies Zofenopril Calcium under UNII 88ZQ329PU2 and CAS 81938-43-4. PubChem reports the molecular formula as C44H44CaN2O8S4 and molecular weight of approximately 897.2 g/mol.
Zofenopril Calcium is a calcium salt containing two zofenopril moieties associated with one calcium ion. The molecular structure contains a proline-derived core, phenylthio functionality and benzoylthio functionality. Zofenopril is a stereochemically defined compound with three stereogenic centers in the parent structure.
The calcium salt is commonly used as the pharmaceutical form of zofenopril. The approved Zofenil product information states that a 30 mg dose of zofenopril calcium corresponds to 28.7 mg of zofenopril, demonstrating the distinction between the salt mass and the equivalent active moiety.
Zofenopril Calcium belongs to the angiotensin-converting enzyme inhibitor class. ACE inhibitors reduce the conversion of angiotensin I to angiotensin II, an active vasoconstrictor involved in regulation of vascular tone and blood pressure.
Following administration, zofenopril is converted to zofenoprilat, its active sulfhydryl-containing metabolite. Zofenoprilat inhibits ACE and consequently reduces angiotensin II-mediated vasoconstriction and aldosterone-related effects. PubChem identifies zofenopril as an ACE inhibitor and prodrug for zofenoprilat.
Zofenopril Calcium is used in pharmaceutical products intended for cardiovascular therapy. Official product information for Zofenil identifies mild to moderate essential hypertension as an indication. It is also indicated in selected patients following acute myocardial infarction, including patients with or without signs and symptoms of heart failure, according to the applicable product information.
Zofenopril Calcium therefore has applications in pharmaceutical development involving:
The exact therapeutic indications and dosing requirements depend on the approved finished product and jurisdiction.
Zofenopril Calcium is a synthetic small-molecule pharmaceutical API requiring controlled chemical synthesis, purification and crystallization. Manufacturing controls are important because the molecule contains multiple stereochemical centers and sulfur-containing functional groups.
The final API should be subjected to appropriate analytical testing to confirm chemical identity, assay, purity, related substances, water or loss on drying, inorganic residue and physical characteristics.
Published manufacturing literature describes purification and calcium-salt formation processes for Zofenopril Calcium. One process specification describes a white solid with liquid chromatographic purity of at least 99.5%, total related substances not more than 0.5%, and any single related substance not more than 0.15%. These figures are useful as a documented process/reference specification but should not be represented as a universal pharmacopoeial standard.
Assay and chromatographic purity are key quality attributes for Zofenopril Calcium API.
A current Thermo Scientific Chemicals specification for Zofenopril Calcium lists HPLC ≥97.5% and loss on drying ≤0.5%. The same source identifies the material as a white to almost white powder and states that its infrared spectrum conforms.
Another published manufacturing reference reports a substantially tighter purity specification of ≥99.5% by HPLC, with total related substances ≤0.5% and individual related substances ≤0.15%.
Because these values come from specific product/process specifications rather than a single universally applicable current pharmacopoeial monograph available in the reviewed public sources, the SDP CMS should distinguish between a verified reference value and the final manufacturer's approved release specification.
Related-substance testing is particularly important for Zofenopril Calcium because impurities may originate from synthesis, incomplete reactions, degradation or stereochemical processes.
HPLC is an appropriate analytical technique for evaluating chromatographic purity and related substances. A published manufacturing specification reports total related substances ≤0.5% and single related substance ≤0.15%.
For a commercial pharmaceutical API, individual impurity limits should be established through the applicable validated analytical method and regulatory specification. It is preferable not to assign unsupported impurity names or numerical limits where a validated product specification is unavailable.
Identification of Zofenopril Calcium can be established using orthogonal analytical techniques. Infrared spectroscopy is commonly used for identity confirmation, while HPLC can confirm chromatographic identity and purity.
A current Thermo Scientific reference specification reports that the infrared spectrum conforms and specifies HPLC purity of ≥97.5%.
Additional characterization techniques such as LC-MS and NMR can be used during development or investigation to confirm molecular structure and identity.
Zofenopril Calcium is described as a white to almost white powder in a current Thermo Scientific specification.
The material is a calcium salt and its physical characteristics can vary with crystallization conditions, particle-size distribution and solid-state form. For pharmaceutical manufacturing, particle size, bulk density and other physical properties may be controlled when relevant to the intended formulation.
Published process information has reported crystalline Zofenopril Calcium with defined particle-size characteristics, demonstrating that solid-state properties can be important manufacturing considerations.
Loss on drying is an important physical-quality parameter for Zofenopril Calcium. A current commercial reference specification reports NMT 0.5% loss on drying.
A published Zofenopril Calcium manufacturing process also reports drying to a loss-on-drying level of ≤0.5% for the final calcium salt.
For SDP documentation, NMT 0.5% is therefore a well-supported numerical reference value for loss on drying.
Zofenopril Calcium is incorporated into oral solid dosage forms, particularly film-coated tablets.
Official product information identifies Zofenil tablets containing 7.5 mg, 15 mg and 30 mg of zofenopril calcium, depending on the presentation. The 30 mg strength contains 30 mg zofenopril calcium corresponding to 28.7 mg zofenopril.
The calcium salt provides the active pharmaceutical ingredient used in these finished pharmaceutical formulations.
Storage requirements for Zofenopril Calcium API should follow the validated manufacturer's stability data, packaging specification and certificate of analysis.
The API should be maintained in suitable pharmaceutical packaging that protects the material from inappropriate environmental exposure. Finished-product storage conditions should not automatically be applied to bulk API because the approved drug product and bulk drug substance can have different stability requirements.
Zofenopril Calcium is an established cardiovascular API used in ACE inhibitor formulations. Its well-defined chemical structure, calcium-salt form and established pharmaceutical applications make it relevant to manufacturers developing oral antihypertensive and cardiovascular products.
For API procurement, important quality attributes include identity, chromatographic assay, related substances, loss on drying, physical appearance and solid-state characteristics. A suitable certificate of analysis should identify the material specifically as Zofenopril Calcium, CAS 81938-43-4, rather than simply reporting the parent compound Zofenopril.
Zofenopril Calcium is a specialized ACE inhibitor API for pharmaceutical manufacturing and formulation applications. It is supplied as a defined calcium salt of zofenopril and is analytically characterized using chromatographic and spectroscopic methods.
For pharmaceutical manufacturers and formulation companies, appropriate API evaluation should include chemical identity, HPLC assay, related-substance profile, moisture control, physical appearance and applicable regulatory documentation.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | NLT 97.5% |
| Loss on Drying | NMT 0.5% |
| Individual Impurity | NMT 0.15% |
| Total Impurities | NMT 0.5% |