Olanzapine Form I is a crystalline polymorphic form of olanzapine, an atypical antipsychotic active pharmaceutical ingredient belonging to the thienobenzodiazepine class. Olanzapine has the molecular formula C₁₇H₂₀N₄S and a molecular weight of approximately 312.43 g/mol. The CAS number of olanzapine is 132539-06-1.
Olanzapine exists in multiple crystalline and solvated forms. Form I is an anhydrous polymorph and has been identified as the thermodynamically stable neat form, making polymorphic control particularly important during pharmaceutical manufacturing and formulation. Form I was selected for commercial development of olanzapine products.
EMA quality documentation describes olanzapine as a pale yellow to yellow crystalline, odourless powder and states that polymorph I is consistently manufactured in the relevant product process.
Olanzapine Form I is particularly relevant from a pharmaceutical solid-state perspective because olanzapine can occur in numerous polymorphic and solvated forms.
Form I is distinguished from other olanzapine crystal forms by analytical techniques such as:
A Form I preparation has been reported with a DSC endothermic peak around 195°C, while PXRD provides characteristic diffraction patterns for distinguishing Form I from Form II.
The reported characteristic Form I d-spacings include approximately 9.9463, 8.5579, 8.2445, 6.8862, 6.3787, 6.2439 and 5.5895 Å, among other peaks. These values are useful for polymorphic identification but should not be treated as a universal release specification without an approved analytical method.
Olanzapine is an atypical antipsychotic API used in pharmaceutical formulations for the management of schizophrenia and bipolar disorder and for other approved psychiatric indications depending on the finished dosage form and regulatory jurisdiction.
Olanzapine Form I is particularly relevant where polymorphic consistency, solid-state stability and reproducibility are important considerations during API and formulation development.
Olanzapine drug substance is evaluated using multiple analytical tests. USP specifications include assay, identification, residue on ignition, heavy metals, organic impurities and water determination. The USP drug-substance monograph specifies 98.0–102.0% assay on an anhydrous, solvent-free basis.
USP also specifies:
Olanzapine Form I should be stored in a well-closed container under controlled pharmaceutical storage conditions, with appropriate protection from moisture and contamination. USP specifies storage at room temperature in well-closed containers.
For Olanzapine Form I, controlling the crystalline form is important because different polymorphs can exhibit different:
Research on olanzapine crystal chemistry confirms that Form I and other polymorphic/solvated forms can be differentiated by solid-state analytical techniques and that Form I is the thermodynamically stable anhydrous form selected for commercial development.
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.1% |
| Heavy Metals | NMT 10 ppm |
| Individual Impurity | NMT 0.10% |
| Total Impurities | NMT 0.40% |
| Melting Point | Approx. 195°C |