Rilpivirine Production Cost Reports

The report provides a detailed analysis essential for establishing a rilpivirine production plant. It encompasses all critical aspects necessary for rilpivirine production, including the cost of rilpivirine production, rilpivirine plant cost, rilpivirine production costs, and the overall rilpivirine production plant cost. Additionally, the study covers specific expenditures associated with setting up and operating a rilpivirine 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.

Rilpivirine is a type of HIV medicine that is used alone or in combination with Complera, Odefsey, Juluca, etc. It works as a major component in antiretroviral therapy for HIV-1 infection, mainly for treatment-naïve adults and adolescents weighing at least 35 kg. It is taken daily as a 25 mg oral tablet with food alongside other antiretrovirals like emtricitabine and tenofovir or dolutegravir.

It stops HIV reverse transcriptase to suppress viral replication and maintain long-term virologic control. It is administered monthly or every two months with cabotegravir and supports maintenance therapy in virologically suppressed patients. This improves adherence by reducing daily pill consumption while maintaining efficiency against susceptible strains. It also finds use as a bridge therapy for tolerability assessment before injectables or in post-exposure prophylaxis regimens.

The market for rilpivirine is driven by global demand for HIV treatments because of growing cases. The expansion of antiretroviral therapy access in developing regions through generics and health programs contributes to its market growth. Its superior adherence with long-acting injectables, reducing daily pill burden, favourable tolerability profiles, and growth in fixed-dose combos boost its usage.

Its utilisation as a bridge therapy for tolerability assessment and in post-exposure prophylaxis regimens fuels its market. The price gaps between innovator products and generics, because of high-volume bulk negotiations in low-income countries impacts industrial rilpivirine procurement. The discounts from initiatives like PEPFAR and CHAI, and cost-effectiveness favouring long-acting options over daily orals impacts its sourcing.

Raw Material for Rilpivirine Production

According to the rilpivirine production plant project report, the key raw materials used in the production of rilpivirine include (2E)-3-(4-amino-3,5-dimethylphenyl)prop-2-enenitrile hydrochloride | 2 methyl tetrahydrofuran | di tert butyl dicarbonate.

Production Process of Rilpivirine

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

1. From (2E)-3-(4-amino-3,5-dimethylphenyl)prop-2-enenitrile hydrochloride: The production process of rilpivirine involves first removing (2E)-3-(4-amino-3,5-dimethylphenyl)prop-2-enenitrile from its hydrochloride salt. This is done using aqueous sodium hydroxide in a biphasic 2 methyl tetrahydrofuran system, separating the organic layer and concentrating to give the free aniline. This is directly protected with di tert butyl dicarbonate under reflux in 2 methyl tetrahydrofuran to form the Boc carbamate intermediate that is then transferred into dimethyl sulfoxide. This protected aniline is reacted with 2,4 dichloropyrimidine in the presence of a strong alkoxide base to form the key Boc protected pyrimidinyl intermediate. This is isolated by quenching into warm water and alcohol, filtration, and optional recrystallisation from n butanol. The resulting intermediate is then coupled with 4 aminobenzonitrile, where nucleophilic substitution on the 2 chloro pyrimidine and concomitant (or subsequent) Boc deprotection occur to give rilpivirine as its hydrochloride salt.

Rilpivirine has the molecular formula C22H18N6 and molecular weight of 366.42 g/mol (402.88 g/mol as hydrochloride salt). It appears as a white to light orange to pale yellow-green powder or crystal with a melting point range of 242-246 degree Celsius. It shows poor aqueous solubility but high solubility in DMSO. It has a logP value of around 4.44, which makes it lipophilic. It has a physiological charge of zero, six hydrogen bond acceptors, two donors, a polar surface area of 97.42 Ų, five rotatable bonds, and a refractivity of 111.74. Its storage requires refrigeration under inert gas to avoid air and heat sensitivity.