Карбидопа

Description

Carbidopa is an anhydrous form of a peripheral DOPA decarboxylase inhibitor, an active ingredient in combination antiparkinsonian therapy. Unlike monohydrate, it contains water of crystallization in an amount corresponding to the anhydrous substance. Chemically it is (S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid. Belongs to the class of amides.

Basic Attributes

• CAS No.: 28860-95-9
• Chemical formula: C10H14N2O4
• Molecular weight: 226.23

Physico-chemical characteristics (according to independent sources)

• Appearance: White or off-white crystalline solid
• Melting point: above 181 °C, according to some sources 203–205 °C, with decomposition
• Density: 1.4 ± 0.1 g/cm3

Mechanism of action and application

Carbidopa irreversibly inhibits the enzyme DOPA decarboxylase at the periphery of the body without passing through the blood-brain barrier due to the pronounced polarity of the molecule. Taken together with levodopa, it reduces the destruction of levodopa in the systemic circulation before it enters the central nervous system, where decarboxylation to dopamine is a therapeutically necessary process. This reduces the frequency and severity of peripheral side effects of levodopa therapy - nausea, vomiting, arrhythmias and orthostatic hypotension - and reduces the required dose of levodopa.

Scope of application

The active substance is used exclusively in combined dosage forms together with levodopa (including triple combinations with catechol-O-methyltransferase inhibitors) for the treatment of Parkinson's disease and symptomatic parkinsonism. Carbidopa has no independent clinical use.

Difference from monohydrate form

Along with the anhydrous substance, carbidopa monohydrate (CAS 38821-49-7, molecular weight 244.24), containing one molecule of water of crystallization, is on the market. The choice between forms is determined by the technology of a particular manufacturer of the finished dosage form: an anhydrous substance facilitates precise control of the moisture content in the formulation, while the hydrated form may have other indicators of stability during storage.

Toxicity

Data on acute oral toxicity for the anhydrous form correspond to those for the hydrated form of the substance: the substance is classified as a substance with moderate acute toxicity when taken orally.

Safety Information

As a pharmaceutical substance, it is subject to handling in accordance with GMP rules and national legislation on the circulation of medicines. When working with powder, it is recommended to use personal respiratory and eye protection to avoid inhaling dust from the active substance.

Storage and transportation conditions

Store in an airtight container in a cool, dry place, protected from direct light, since the catechol hydroxyl group of the molecule is sensitive to oxidation in air. Transportation is carried out in accordance with the requirements for the transportation of pharmaceutical substances.

Difference from hydrate form

The monohydrate form of carbidopa (CAS 38821-49-7) with a molecular weight of 244.24, including one molecule of water of crystallization, is on the market in parallel. The anhydrous form with CAS 28860-95-9 and weight 226.23 is preferred where the production technology of the finished dosage form requires precise control of the moisture content in the substance, since the water of crystallization of the hydration form can affect the stability of the formulation during storage and the accuracy of dosing of the active substance.

Regulatory status

Carbidopa as an active pharmaceutical substance is subject to state registration and is included in the pharmacopoeial monographs of the main regulatory jurisdictions. The production and circulation of the substance is controlled by good manufacturing practice (GMP) requirements, batch analysis certificates and traceability requirements for raw materials used by pharmaceutical companies to produce finished forms.