Ambrisentan Production Cost Reports

The report provides a detailed analysis essential for establishing an ambrisentan production plant. It encompasses all critical aspects necessary for ambrisentan production, including the cost of ambrisentan production, ambrisentan plant cost, ambrisentan production costs, and the overall ambrisentan production plant cost. Additionally, the study covers specific expenditures associated with setting up and operating an ambrisentan production plant. These encompass production processes, raw material requirements, utility requirements, infrastructure needs, machinery and technology requirements, manpower requirements, packaging requirements, transportation requirements, and more.

Ambrisentan is a selective endothelin receptor antagonist (ERA) that is used to treat pulmonary arterial hypertension (PAH). It improves exercise capacity, delays clinical worsening like hospitalisation or death, and enhances quality of life in patients. It is administered orally once daily and is used alone or combined with tadalafil to reduce disease progression risks.

It lowers pulmonary vascular resistance and boosts cardiac index via vasodilation of lung vessels. It is also used to treat pulmonary arterial hypertension in teens and kids weighing more than 50 kg. It supports people with PAH linked to repaired heart defects from birth. Its common side effects include swelling from fluid retention, rapid weight gain, nasal congestion, flushing, headaches, sore throat, palpitations, mild anaemia, constipation, and cough.

The market for ambrisentan is driven by rising cases of pulmonary arterial hypertension (PAH). The rise in ageing populations and better diagnostics fuels demand for endothelin receptor antagonists. The usage of combination therapies, awareness campaigns, and healthcare investments contributes to its market. Its utilisation in the treatment of pulmonary arterial hypertension in teens and kids boosts its market.

The industrial ambrisentan procurement is affected by high speciality pricing under REMS programs, restricting distribution to certified pharmacies. The regulatory hurdles (like pregnancy category that needs monitoring), API synthesis reliance on intermediates and supply chain instabilities like tender delays or shortages affect its sourcing strategies.

Raw Material for Ambrisentan Production

According to the ambrisentan production plant project report, the key raw materials used in the production of ambrisentan include benzophenone, methyl chloroacetate, sodium methanolate, methanol, p-toluenesulfonic acid, and (S)-dehydroabietylamine.

Production Process of Ambrisentan

The extensive ambrisentan production cost report consists of the following major industrial production process:

1. From benzophenone and methyl chloroacetate: The production process of ambrisentan starts with the preparation of methyl 3,3-diphenyloxirane-2-carboxylate. It is synthesised by a reaction between benzophenone and methyl chloroacetate in dry THF with sodium methanolate in dry THF. This epoxide goes through acid-catalysed ring opening with methanol (using p-toluenesulfonic acid) to form the corresponding ester. This is followed by base hydrolysis with sodium hydroxide and acidification to produce racemic 2-hydroxy-3-methoxy-3,3-diphenylpropanoic acid. After that, chiral resolution is achieved by dissolving the racemic acid in methyl tertiary butyl ether and refluxing with (S)-dehydroabietylamine to form (S)-acid diastereomeric salt. This is filtered, and the enantiopure (S)-acid is obtained with acid treatment. Finally, (S)-acid is dissolved in DMF with base, which is added to 4,6-dimethyl-2-(methylsulfonyl)pyrimidine in DMF, to get ambrisentan as the final product.

Ambrisentan has the molecular formula of C22H22N2O4 with a molecular weight of 378.43 g/mol. It is a white to off-white crystalline powder with a melting point of 178 degree Celsius. It has a specific rotation of [α]^D +170 to +190 degree (c=0.5, MeOH) or +173 degree with a pKa value of  0.97±0.10. It has a boiling point of 551 degree Celsius with a density of 1.228±0.06 g/cm³. It has low solubility in water but is slightly soluble in DMSO and methanol. It has 7 rotatable bonds, a topological polar surface area of 81.54 Ų, and poor aqueous solubility. Its storage requires sealed, dry, 2-8 degree Celsius conditions as a solid stable under refrigeration.