Моногидрат карбидопы

Description

Carbidopa monohydrate is a crystalline hydrate of carbidopa, an inhibitor of peripheral aromatic L-amino acid decarboxylase (DOPA decarboxylase). It is used in combination therapy for Parkinson's disease with levodopa, reducing the peripheral conversion of levodopa to dopamine and thereby increasing the proportion of the dose reaching the central nervous system. Belongs to the class of amides.

Basic Attributes

• CAS No.: 38821-49-7
• Chemical formula: C10H14N2O4 H2O
• Molecular weight: 244.24
• Exact weight: 244.105927
• UNII: MNX7R8C5VO
• NCI Thesaurus Code: C47431
• HS code: 2928000090
• PSA specifications: 117 Å2

Physico-chemical characteristics

• Density: 1.42 g/cm3
• Boiling point: 528.7 °C at 760 mm Hg. Art.
• Flash point: 273.5 °C

Mechanism of action and application

Carbidopa irreversibly inhibits DOPA decarboxylase outside the blood-brain barrier, without penetrating into the central nervous system. This reduces the systemic formation of dopamine from levodopa in the periphery, reduces the severity of side effects (nausea, vomiting, orthostatic hypotension) and allows the use of lower doses of levodopa to achieve a therapeutic effect in the brain. The combination of carbidopa/levodopa is the standard treatment for Parkinson's disease and parkinsonism of various etiologies. The active substance is used in the production of finished dosage forms by pharmaceutical companies.

Toxicity

• Oral LD50 in rats: 4810 mg/kg
• Oral LD50 in mice: 1750 mg/kg

Flammability and Stability Characteristics

When thermally decomposed, it releases toxic fumes of nitrogen oxide. Hazard category: irritant.

Safety Information

• Hazard category: irritant
• Transport codes: NONH for all modes of transport
• WGK Germany: 3
• RTECS number: MW5300000
• Storage features: low-temperature warehouse, ventilated, dry
• Precautions: P305+P351+P338
• Hazard Statements: H319
• GHS classification: H302 (52.22% of notifications) - harmful if swallowed; precautions P261, P264, P270, P271, P273, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501. The data is aggregated for 90 companies from 9 notifications to the ECHA C&L register.

Storage and transportation conditions

Store in a cool, dry, ventilated area, in the original sealed container, away from sources of moisture - the substance forms a crystalline hydrate and is sensitive to changes in air humidity. Formally, it does not apply to dangerous goods during transportation (code NONH), however, when working with the powder, use eye and respiratory protection due to its irritating effect.

Features of the hydrate form

Unlike anhydrous carbidopa, the monohydrate form includes one molecule of water of crystallization per molecule of the active substance, which is reflected in a higher molecular weight (244.24 versus 226.23 for the anhydrous substance) and affects the recalculation of the dosage in the production of finished dosage forms. The choice of a hydrated or anhydrous form is determined by the technology of a particular manufacturer and the requirements for the stability of the finished formulation during storage.

Industrial purpose

The substance is supplied to pharmaceutical companies for inclusion in tablets and capsules of carbidopa/levodopa combination preparations, including long-acting and triple combinations with catechol-O-methyltransferase inhibitors. The circulation of the substance as an active pharmaceutical substance is regulated by the requirements of good manufacturing practice (GMP) and national pharmaceutical legislation.