Tiotropium Bromide is a long-acting muscarinic antagonist (LAMA) used as an active pharmaceutical ingredient in inhalation medicines for the maintenance treatment of airflow obstruction associated with chronic obstructive pulmonary disease (COPD). The pharmaceutical substance is commonly handled as tiotropium bromide monohydrate, which is the form used in marketed inhalation products. PubChem identifies the monohydrate as a quaternary ammonium bromide salt with molecular formula C₁₉H₂₄BrNO₅S₂ and molecular weight 490.40 g/mol.
Tiotropium is a quaternary ammonium derivative with antimuscarinic activity. After inhalation, it binds to muscarinic receptors in airway smooth muscle, with prolonged activity at M3 receptors, helping reduce cholinergic bronchoconstriction and promote sustained bronchodilation. Tiotropium bromide is used primarily in maintenance respiratory therapy rather than for rapid relief of acute bronchospasm.
The API is available in different solid-state forms, including the anhydrous bromide and monohydrate. For pharmaceutical manufacturing, the exact hydrate state should be specified because the molecular weight, water content and assay basis differ. The USP 2025 material identifies both tiotropium bromide and tiotropium bromide monohydrate.
Tiotropium Bromide Monohydrate has the molecular formula C₁₉H₂₂BrNO₄S₂·H₂O and molecular weight approximately 490.43 g/mol. The corresponding anhydrous tiotropium bromide has molecular weight approximately 472.41 g/mol. The monohydrate is the pharmaceutical form commonly referenced for respiratory-grade material.
The compound contains a permanently charged quaternary ammonium center and a bromide counterion. Its stereochemical configuration is important for pharmaceutical activity and is controlled as part of API manufacturing and analytical characterization.
Tiotropium produces prolonged bronchodilation by antagonizing muscarinic acetylcholine receptors in the respiratory tract. Its relatively prolonged interaction with M3 receptors reduces acetylcholine-mediated contraction of airway smooth muscle. This mechanism makes Tiotropium Bromide an important API for long-acting inhaled bronchodilator formulations.
Tiotropium Bromide API is primarily used in the manufacture of inhalation medicines intended for:
FDA materials specifically identify tiotropium bromide monohydrate in inhalation products and describe analytical considerations for tiotropium inhalation dosage forms.
Quality control of Tiotropium Bromide API requires identity, assay, water determination and organic impurity testing. The USP 2025 monograph specifies an assay range of 98.0–102.0% of tiotropium bromide calculated on the anhydrous basis and a water limit of NMT 4.0%. Identification includes infrared spectroscopy, chromatographic retention-time comparison and bromide identification.
The European Pharmacopoeia material additionally describes controls for related substances, heavy metals, water and sulfated ash. The cited monograph specifies water 2.5–4.0%, heavy metals NMT 10 ppm, and sulfated ash NMT 0.1%, with organic impurities controlled chromatographically.
Because pharmacopoeial requirements can change by edition and jurisdiction, the applicable current monograph and customer's registered specification should be used for commercial release testing.
Commercial Tiotropium Bromide API manufacturing requires controlled synthesis, purification, crystallization and solid-state management to obtain the required stereochemical and chemical purity. Particular attention is required for hydrate control because the API may be supplied as the monohydrate. Analytical controls generally include chromatographic purity, assay, water content, identification and inorganic impurity testing.
Tiotropium Bromide Monohydrate is described as a solid pharmaceutical substance with a molecular weight of approximately 490.43 g/mol. PubChem lists the monohydrate under CAS 139404-48-1, while 411207-31-3 is also associated with the hydrate form in regulatory/chemical databases.
The API has limited aqueous solubility characteristics and is handled according to pharmaceutical-grade manufacturing and formulation requirements. A commercial analytical reference lists it as sparingly soluble in methanol; such qualitative solubility information should not be confused with a universal pharmacopoeial release specification.
Tiotropium Bromide API should be packaged in suitable, well-closed/tight pharmaceutical containers that protect the material from moisture, contamination and excessive environmental exposure. USP specifies storage in tight containers.
Storage conditions should follow the approved API specification, stability data and applicable regulatory documentation.
Typical pharmaceutical API documentation may include:
A qualified Tiotropium Bromide API manufacturer should maintain robust controls for stereochemistry, hydrate state, assay, organic impurities, water content and elemental impurities. Manufacturing under appropriate pharmaceutical quality systems, supported by validated analytical procedures and batch-specific documentation, helps ensure consistency for inhalation-product manufacturers.
Tiotropium Bromide is particularly sensitive to correct control of the monohydrate form, so procurement specifications should clearly identify whether the requirement is for anhydrous tiotropium bromide or tiotropium bromide monohydrate.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Residue on Ignition | NMT 0.1% |
| Heavy Metals | NMT 10 ppm |
| Total Impurities | NMT 0.3% |
| Water Content | 2.5–4.0% |