Empagliflozin is an active pharmaceutical ingredient functioning as a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. It blocks glucose reabsorption in the renal proximal tubules, increasing urinary glucose excretion to lower blood glucose levels in adult patients diagnosed with type 2 diabetes mellitus. Production utilizes multi-step organic synthesis starting from validated chiral intermediates, followed by purification via crystallization to meet stringent purity thresholds. Finished active substance exists as a white to off-white crystalline powder, sparingly soluble in water and soluble in ethanol.
Product Information
|
Parameter |
Technical Specification |
|
IUPAC Name |
(1S)-1,5-anhydro-1-[4-chloro-3-[[4-[((3S)-tetrahydrofuran-3-yl)oxy]phenyl]methyl]phenyl]-D-glucitol |
|
CAS Registry Number |
864070-44-0 |
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Grade Standard |
Commercial Grade / USP/EP Compliant |
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Appearance |
White to off-white powder |
|
Melting Point |
148°C to 152°C |
|
Chiral Purity |
≤ 99.5 % by HPLC |
|
Loss on Drying |
≤ 0.5 % |
Quality & Specification
Assay (Calculated on anhydrous basis): $98.0\% \text{ to } 102.0\%$ determined via high-performance liquid chromatography.
Chiral Purity: Enantiomeric excess verified by chiral column chromatography to restrict undesired stereoisomers.
Residual Solvents: Controlled strictly below ICH Q3C limits for Class 3 solvents (e.g., ethanol, ethyl acetate) using headspace gas chromatography.
Heavy Metals: Total heavy metals quantified below 10 ppm via inductively coupled plasma mass spectrometry.
Microbial Limits: Total aerobic microbial count and total yeast/mold count monitored per pharmacopeial microbial enumeration tests.
Impurity Profile: Individual known impurities controlled at $\le 0.10\%$; total impurities limited to ≤ 0.5 %.
Manufacturing & Supply
Facility Standards: Synthesized within dedicated, isolated reaction suites operating under current Good Manufacturing Practices (cGMP).
Batch Capacity: Commercial scale production batches ranging from 100 kg to 500 kg per run.
Process Controls: In-process controls monitor reaction completion, temperature gradients, centrifugation parameters, and vacuum drying rates.
Traceability: Full raw material lot tracking from verified chemical starting materials through final packaging.
Supply Stability: Continuous multi-campaign scheduling designed to maintain consistent stock levels and meet scheduled annual volume demands.
Documentation
Drug Master File (DMF) available for reference by authorized regulatory authorities.
Certificate of Analysis (CoA) issued with every individual production batch.
Complete impurity profile reports, residual solvent validation data, and stability study summaries.
Written assurances confirming absence of Genotoxic Impurities (GTI), TSE/BSE compliance, and melamine-free status.
Packaging
Primary Packaging: Double-layer medical-grade low-density polyethylene (LDPE) bags, heat-sealed under controlled humidity conditions.
Secondary Packaging: Rigid fiber drums or stainless steel containers providing physical protection and light barrier properties.
Desiccant Integration: Food-grade silica gel packets placed between primary and secondary packaging layers to control residual moisture.
Labeling: Exterior drum labels display product nomenclature, CAS number, batch number, net weight, gross weight, manufacturing date, retest date, and storage instructions.
Pharmaceutical Application
Type 2 Diabetes Mellitus Management: Used as an adjunct to diet and exercise to improve glycemic control in adult patients.
Cardiovascular Risk Reduction: Incorporated into formulations intended to reduce the risk of cardiovascular death in patients diagnosed with type 2 diabetes and established cardiovascular disease.
Heart Failure Treatment: Serves as the active ingredient in medications prescribed to reduce the risk of cardiovascular death and hospitalization in adult patients with heart failure.
Combination Therapy Formulations: Blended with metformin hydrochloride or linagliptin to produce fixed-dose combination tablets for multi-pathway glycemic control.
Renal Protection Indications: Utilized in dosage forms formulated to slow the progression of diabetic kidney disease and reduce sustained eGFR decline.
FAQ
Q: What is the standard batch size available for commercial orders?
A: Standard commercial production runs generate batches scaled from 100 kg to 500 kg, with custom batch sizing available upon formal agreement.
Q: Is a Drug Master File accessible for regulatory review?
A: Yes, a comprehensive Drug Master File is maintained and available for submission support under appropriate confidentiality arrangements.
Q: What storage conditions are required to maintain stability?
A: Store in tightly closed containers protected from moisture and light, maintained at controlled room temperature between 15°C and 30°C.
Q: How are chiral purity and stereoisomers controlled during synthesis?
A: Chiral purity is maintained through stereoselective reduction steps and verified via chiral HPLC analysis on every isolated lot.
Q: What is the standard retest period designated for this active ingredient?
A: The established retest period is 24 months from the date of manufacture when stored in unopened, original packaging under recommended conditions.
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