Pimecrolimus is a semi-synthetic macrolactam immunomodulatory active pharmaceutical ingredient used primarily in topical dermatological formulations. Pimecrolimus CAS Number 137071-32-0 identifies the active pharmaceutical ingredient, which has the molecular formula C43H68ClNO11 and a molecular weight of 810.46 g/mol according to the USP monograph. PubChem reports a molecular weight of approximately 810.4 g/mol and identifies the FDA GSRS UNII as 7KYV510875.
Pimecrolimus belongs to the calcineurin-inhibitor class of immunomodulatory compounds. It is structurally related to ascomycin-derived macrolide compounds and is formulated primarily as a topical cream. Current U.S. labeling describes pimecrolimus as a white to off-white fine crystalline powder. It is soluble in methanol and ethanol and insoluble in water; another current label provides a more detailed solvent profile, describing it as freely soluble in methyl ethyl ketone, methyl isobutyl ketone, dichloromethane and tetrahydrofuran, soluble in acetone, methanol, ethanol, acetonitrile and toluene, sparingly soluble in isopropanol, and practically insoluble in water.
The pharmaceutical significance of pimecrolimus comes from its selective immunomodulatory activity. Pimecrolimus binds with high affinity to FKBP-12 and the resulting complex inhibits calcineurin, thereby interfering with T-cell activation and cytokine production. This pharmacological profile supports its use in topical treatment of inflammatory skin conditions. FDA labeling identifies pimecrolimus cream 1% as a second-line treatment for mild-to-moderate atopic dermatitis in specified patients aged 2 years and older.
Pimecrolimus is a structurally complex macrolide containing one chlorine atom, multiple oxygen functionalities, and numerous stereogenic centers. Its complexity makes accurate analytical characterization particularly important during API manufacturing. The USP monograph specifically defines pimecrolimus using the formula C43H68ClNO11 and requires assay determination on an anhydrous and solvent-free basis.
A significant feature of pimecrolimus quality control is its related-substance profile. The current USP monograph specifically identifies ascomycin, desmethylpimecrolimus, and pimecrolimus triene analog among the impurities controlled by the chromatographic procedure. Pimecrolimus tautomer I and tautomer II are included in the assay calculation rather than being treated as separate impurities for the total-impurity acceptance criterion.
| Product Parameter | Pimecrolimus |
|---|---|
| CAS Number | 137071-32-0 |
| UNII | 7KYV510875 |
| Molecular Formula | C43H68ClNO11 |
| Molecular Weight | 810.46 g/mol |
| Exact Mass | 809.4481 Da |
| XLogP3 | 3.8 |
| Hydrogen Bond Donors | 2 |
| Hydrogen Bond Acceptors | 11 |
| Rotatable Bonds | 6 |
| Topological Polar Surface Area | 158 Ų |
| Appearance | White to off-white fine crystalline powder |
| Water Solubility | Insoluble / practically insoluble |
| Methanol | Soluble |
| Ethanol | Soluble |
| API Class | Calcineurin inhibitor / immunomodulator |
| Primary Pharmaceutical Application | Topical dermatological formulations |
PubChem supports the chemical identity and calculated physicochemical descriptors, while current FDA/DailyMed labeling supports the appearance and solvent-solubility profile.
Pimecrolimus is primarily incorporated into topical pharmaceutical products for dermatological use. The commercially established dosage form is Pimecrolimus Cream 1%, containing 10 mg of pimecrolimus per gram of cream. Current U.S. labeling identifies this formulation for short-term and non-continuous chronic treatment of mild-to-moderate atopic dermatitis in non-immunocompromised adults and children 2 years of age and older when other topical prescription treatments have not provided an adequate response or are otherwise inadvisable.
The API's mechanism is associated with inhibition of calcineurin-mediated T-cell activation. Pimecrolimus-FKBP12 complexes inhibit calcineurin and consequently reduce transcription of several inflammatory cytokines. This activity is relevant to its topical immunomodulatory effect in inflammatory skin disorders.
The USP Pimecrolimus monograph provides considerably more useful numerical information than generic commercial specifications. The current USP definition requires NLT 98.0% and NMT 102.0% pimecrolimus, calculated on an anhydrous and solvent-free basis. The USP assay is an LC method using UV detection at 210 nm.
USP also specifies Residue on Ignition NMT 0.1%, Water Determination NMT 0.5%, and specific rotation of −45° to −55° at 20°C, calculated on the anhydrous and solvent-free basis. The monograph further establishes individual impurity limits and a total impurity limit.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.10% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 0.5% |
| Specific Rotation | −45° to −55° at 20°C |