| Condition | Initial | 3 mo | 6 mo | 9 mo | 12 mo | 18 mo | 24 mo | 36 mo |
|---|---|---|---|---|---|---|---|---|
| Long-Term 30°C/65% RH |
XY | X | X | X | X | X | X | (X) |
| Accelerated 40°C/75% RH |
XY | X | X | — | — | — | — | — |
X = Description + Assay + Impurities | Y = Particle Size Distribution | (X) = Optional Testing
| Test | Acceptance Criteria | Initial (CAT1) | Initial (CAT2) | Initial (CAT3) | 36m (CAT1) | 36m (CAT2) | 36m (CAT3) |
|---|---|---|---|---|---|---|---|
| Description | A white to brown powder | Complies | Complies | Complies | Complies | Complies | Complies |
| Assay | 98.0 – 102.0% w/w | 100.1 | 100.2 | 99.9 | 99.8 | 99.7 | 99.9 |
| Total Impurities | ≤ 1.5% w/w | 0.10 | 0.12 | 0.11 | 0.35 | 0.38 | 0.31 |
| Particle Size (d50) | ≤ 200 μm | 145 | 152 | 148 | NT | NT | NT |
| Test | Acceptance Criteria | Initial (CAT1) | Initial (CAT2) | Initial (CAT3) | 6m (CAT1) | 6m (CAT2) | 6m (CAT3) |
|---|---|---|---|---|---|---|---|
| Description | A white to brown powder | Complies | Complies | Complies | Complies | Complies | Complies |
| Assay | 98.0 – 102.0% w/w | 100.1 | 100.2 | 99.9 | 99.5 | 99.4 | 99.6 |
| Total Impurities | ≤ 1.5% w/w | 0.10 | 0.12 | 0.11 | 0.45 | 0.48 | 0.41 |
| Property | Value |
|---|---|
| Appearance | White to slightly yellow powder |
| Solubility (Purified Water, PhEur) | Freely soluble (23 - 27 mg/mL) |
| Solubility (Acetone, PhEur) | Slightly soluble (2 - 3 mg/mL) |
| Solubility (Ethanol, PhEur) | Soluble (15 - 17 mg/mL) |
| pH in aqueous solution | 6.7 - 6.8 (10 mg/ml at 25°C) |
| Hygroscopy | Hygroscopic |
| Stereochemistry | One asymmetric center and one axis of chirality; (S,M) - enantiomer |
| Test Parameter | Method | Acceptance Criteria |
|---|---|---|
| Description | Visual inspection | A white to brown powder |
| Identification | Identification by IR spectroscopy / HPLC | Conforms with reference |
| Assay | Assay by LC | 98% to 102% w/w |
| Drug Substance Related Organic Impurities | Organic impurities by LC | Total impurities ≤ 2.0% w/w |
| Mutagenic Impurities | Impurity 5 content by LC-MS | ≤ 50 ppm |
| Enantiomeric Purity | Enantiomeric purity by LC | ≥ 99.6% |
| Residual Solvents | Residual solvents by headspace GC | Solvent 1 ≤ 0.1% w/w, Solvent 2 ≤ 2.0% w/w |
| Water Content | USP Karl Fischer titration | ≤ 1.0% w/w |
| Particle Size Distribution | Laser diffraction | D(v,0.9) ≤ 319 µm, D(v,0.5) ≤ 145 µm, D(v,0.1) ≤ 20 µm |