112529-15-4 Pioglitazone Hydrochloride

✅ Pharmaceutical API (Primary Application)

1. Type 2 Diabetes Mellitus (T2DM): Monotherapy for adult patients with T2DM who cannot achieve adequate glycemic control with diet and exercise alone; also used as combination therapy with metformin, sulfonylureas, or insulin to improve blood glucose management (reduces HbA1c by 0.5–1.5%).

2. Dyslipidemia Associated with T2DM: Improves lipid profiles by reducing triglyceride levels and increasing high-density lipoprotein cholesterol (HDL-C) in T2DM patients with mixed dyslipidemia.

3. Non-alcoholic Fatty Liver Disease (NAFLD): Off-label use for the treatment of NAFLD in insulin-resistant patients, as it reduces hepatic steatosis and inflammation by improving insulin sensitivity.

✅ Formulation Development

1. Commercial dosage forms: Immediate-release tablets (15 mg, 30 mg, 45 mg), oral dispersible tablets, and fixed-dose combination tablets (with metformin).

2. R&D focus: Extended-release formulations to reduce dosing frequency and improve patient compliance; pediatric formulations for children with T2DM.

✅ Biomedical Research

1. Preclinical studies on PPARγ signaling pathways, insulin resistance mechanisms, and the role of adiponectin in glucose metabolism.

2. Research on therapeutic effects in polycystic ovary syndrome (PCOS) (improves insulin sensitivity and ovulation) and cardiovascular diseases (reduces atherosclerosis risk in T2DM patients).

▶ API Raw Material Packaging (GMP Standard)

▸ Lab/Research Grade: Sealed amber glass vials with Teflon-lined screw caps, specifications: 1 g, 5 g, 10 g, 25 g, 50 g, 100 g; purity ≥99.5%, vacuum-sealed to prevent moisture absorption and oxidation.

▸ Industrial/Pharmaceutical Grade: HDPE plastic drums or fiber drums with double polyethylene (PE) inner liners, specifications: 1 kg, 5 kg, 25 kg, 50 kg; drum labels include CAS number, batch number, purity, net weight, storage conditions, GMP certification, and hazard warnings (e.g., avoid prolonged skin contact).

▸ Customized Export Packaging: 10 g/50 g/100 g aluminum foil bags for small-batch shipments; labeled with international transportation marks and compliance with ICH Q7 standards.

▶ Finished Product Packaging

▸ Immediate-release tablets: HDPE bottles with child-resistant caps (30/60/90 tablets per bottle) or aluminum blister packs (10 tablets per blister, 3/6 blisters per box).

▸ Fixed-dose combination tablets: Blister packs with moisture-proof aluminum foil, 28/30 tablets per box, labeled with dual drug dosage information.

▶ Storage & Shelf Life Requirements

1. API storage: 25°C ± 2°C (short-term storage: 15–30°C), protected from light and moisture, stored in a well-ventilated warehouse; avoid contact with strong acids, bases, and oxidants; shelf life 24 months under sealed conditions.

2. Transportation: Normal temperature transportation for both API and finished products; use moisture-proof packaging (e.g., desiccant packs in containers) to prevent degradation.

Raw Materials: 2,4-thiazolidinedione, 4-(2-bromoethyl)benzoic acid ethyl ester, 2,5-dimethylaniline, hydrochloric acid

Steps (5-step scalable synthesis):

1. Esterification & Amination: React 4-(2-bromoethyl)benzoic acid with ethanol under acidic catalysis to form ethyl 4-(2-bromoethyl)benzoate; then react with 2,5-dimethylaniline in the presence of potassium carbonate (K₂CO₃) as acid scavenger, solvent: acetonitrile, temperature: 70–80°C, obtain intermediate ethyl 4-(2-(2,5-dimethylphenylamino)ethyl)benzoate.

2. Condensation with Thiazolidinedione: Condense the above intermediate with 2,4-thiazolidinedione in the presence of sodium methoxide (NaOCH₃) catalyst, solvent: methanol/toluene mixture, temperature: 80–90°C, generate 5-[4-[2-(2,5-dimethylphenylamino)ethyl]benzyl]-2,4-thiazolidinedione (pioglitazone free base precursor).

3. Cyclization & Purification: Heat the precursor in glacial acetic acid to promote intramolecular cyclization, then recrystallize from ethanol/water mixture to obtain high-purity pioglitazone free base (purity ≥99.0%).

4. Salt Formation: Dissolve the pioglitazone free base in isopropanol, add concentrated hydrochloric acid dropwise (molar ratio 1:1) under stirring at 20–30°C, adjust pH to 2–3, and cool to 0–5°C to induce crystallization.

5. Drying & Milling: Filter the crystalline precipitate, wash with cold isopropanol, and dry under vacuum at 50–60°C to obtain pioglitazone hydrochloride white crystalline powder (final purity ≥99.5%).

Advantages: Low-cost raw materials, mild reaction conditions, no ultra-low temperature requirements, easy industrial scale-up, and minimal by-product generation.