Clomipramine CAS 303-49-1 — China API Manufacturer | ChP/USP/EP R&D to Production

Product Overview & China Manufacturing Landscape

Clomipramine is a tricyclic antidepressant (TCA) with potent serotonin reuptake inhibition properties, primarily prescribed for obsessive-compulsive disorder (OCD), major depressive disorder, panic disorder, and certain chronic pain conditions. With CAS number 303-49-1 and molecular formula C₁₉H₂₃ClN₂, clomipramine (as the free base) and its hydrochloride salt form are included on the WHO Essential Medicines List. China maintains approximately 8 NMPA-registered manufacturers of clomipramine API, with combined annual production capacity of around 200 metric tons. Our facility in Jiangsu Province specializes in tricyclic compound chemistry, with established production lines for multiple TCA APIs. China’s competitive advantage in clomipramine manufacturing stems from mature dibenzazepine ring synthesis technology and integrated supply chains for chlorinated aromatic intermediates.

Our Manufacturing Process & Facility Standards

Clomipramine synthesis involves construction of the 3-chloro-10,11-dihydro-5H-dibenz[b,f]azepine tricyclic core, followed by N-alkylation with 3-(dimethylamino)propyl chloride to introduce the side chain. The synthesis requires 5-7 steps from commercially available starting materials, with overall yields of 35-45%. Critical process parameters include the chlorination regioselectivity for the 3-position, cyclization conditions for dibenzazepine ring formation, and crystallization solvent system selection for polymorphic control. Our quality-controlled production facility provides 14,000 square meters of manufacturing space with ISO 14644-1 Class 7 cleanroom environments for final processing. Reactor systems include 3,000-8,000 liter glass-lined vessels with automated temperature control and inert atmosphere capability. In-process quality controls encompass HPLC purity checks at each intermediate stage, GC headspace analysis for residual solvents, chlorine content verification by argentometric titration, and final product particle size analysis. Our manufacturing process consistently achieves Cpk values above 1.5 for critical quality attributes, with assay RSD below 0.8% over 80+ commercial batches.

Quality Standards & Multi-Pharmacopeial Compliance

Our clomipramine API (free base) and clomipramine hydrochloride comply with ChP 2020, USP-NF, EP 11.0, and BP specifications. Typical assay values are 99.0-100.5% on a dried basis. Key quality parameters include: related substances by HPLC (each individual impurity ≤0.2%, total ≤0.5%), residual solvents per ICH Q3C with specific attention to toluene and DMF, loss on drying (≤0.5%), heavy metals (≤10 ppm by ICP-MS), sulfated ash (≤0.1%), and chlorine content within theoretical range. For the hydrochloride salt, pH of solution and water content are additionally controlled. Polymorphic form is verified by XRPD with each batch. Genotoxic impurity assessment per ICH M7 has been completed, with all identified mutagenic alerts controlled below TTC-based acceptable intakes. Every shipment includes a complete COA tailored to the customer-specified pharmacopeial standard. Stability data per ICH Q1A confirm 48-month shelf life.

Regulatory Documentation & Registration Support

Our clomipramine regulatory portfolio includes: NMPA drug registration certificate, Chinese DMF, US FDA Type II DMF, European ASMF for customer CEP/MAA referencing, and current quality certificates from Chinese provincial authority. Our facility holds FDA establishment registration. Available regulatory documentation extends to: complete CTD Module 3.2.S dossier, process validation report, analytical method validation per ICH Q2, impurity characterization with structural elucidation data, ICH M7 mutagenic impurity risk assessment, ICH Q3D elemental impurity assessment, and stability data in multiple packaging configurations. Our regulatory team has experience supporting customer registrations across multiple markets and provides dedicated assistance with technical dossier preparation, regulatory strategy for market entry, and coordination of manufacturing site inspections by foreign regulatory authorities.

Packaging, Storage & Global Logistics

Clomipramine API is packaged in double-layer polyethylene bags within aluminum drums, providing protection against moisture and light. Standard packaging sizes include 1 kg, 5 kg, and 25 kg per drum. Storage conditions require controlled room temperature (below 25°C) in a dry, light-protected environment, with a validated shelf life of 48 months. We arrange international shipments through our logistics partnerships to destinations worldwide. Typical transit times include: 28-35 days to European ports by sea freight, 14-18 days by China-Europe rail, 20-25 days to South American ports, and 3-7 days by air freight. Our logistics team provides door-to-door service coordination including customs documentation preparation, certificate of origin and free sale certificate issuance, and temperature monitoring device inclusion for shipments to tropical destinations. Standard and expedited shipping options are available based on customer urgency requirements.

Competitive Pricing & Supply Reliability

Our established tricyclic compound manufacturing platform delivers favorable production economics for clomipramine, reflected in our competitive competitive pricing. Customers benefit from direct manufacturer pricing without trading company intermediaries, typically achieving 30-45% cost savings versus European sources. MOQ is 10 kg for initial evaluation orders, with standard commercial orders from 50 kg. We offer flexible pricing arrangements including quarterly price lists, annual fixed-price contracts for committed volumes, and spot pricing for urgent requirements. Our production capacity supports 5-10 metric tons monthly output. Strategic raw material inventory covers 5 months of production, and we maintain finished API safety stock of 2 metric tons for rapid order fulfillment. Long-term supply agreements with guaranteed allocation and pricing are available for customers seeking supply security for this essential medicine API.

Product Specifications