Olanzapine Form II 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 molecular weight 312.43 g/mol, with CAS Number 132539-06-1.
The historically designated Olanzapine Form II is an anhydrous, solvate-free crystalline polymorph. The original polymorph patent describes this form as stable and suitable for pharmaceutical formulations.
Olanzapine exhibits multiple polymorphic and solvated crystal forms. Form II can be distinguished from Form I by powder X-ray diffraction (PXRD/XRPD), FT-IR and other solid-state characterization techniques.
A characteristic PXRD peak reported for the historically designated Form II occurs at approximately:
These values originate from polymorph characterization and should be used as identification/reference data rather than a universal release specification.
FT-IR can also differentiate the polymorphs. Published process literature reports a characteristic Form II region around 886 cm⁻¹, which is absent in Form I, while Form I has a nearby characteristic region around 903 cm⁻¹. The reported FT-IR method could detect Form II contamination in Form I at approximately the 2% level.
Olanzapine is used as an active pharmaceutical ingredient in medicines for approved psychiatric indications including schizophrenia and bipolar disorder, depending on the dosage form and applicable regulatory authorization.
Olanzapine polymorph control is important because crystal form can influence physical and pharmaceutical properties such as:
Olanzapine API quality can be evaluated using chromatographic, spectroscopic and solid-state techniques. The USP monograph provides numerical limits for several conventional API quality attributes.
The USP assay requirement is 98.0%–102.0% on an anhydrous, solvent-free basis. USP also specifies NMT 0.1% residue on ignition, NMT 10 ppm heavy metals, and NMT 1.0% water.
For a product specifically marketed as Olanzapine Form II, polymorphic identity should preferably be established using PXRD/XRPD together with a suitable complementary technique such as FT-IR or DSC.
This is particularly important because historical olanzapine literature contains different naming conventions for Form I and Form II. Modern scientific literature explains that the stable polymorph was ultimately designated Form I in Lilly's regulatory nomenclature, while the metastable form became Form II.
Therefore, the actual PXRD reference pattern and internal approved specification should control the CMS product identity, rather than the form name alone.
| 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% |
| Water Content | NMT 1.0% |