Acetazolamide API (Active Pharmaceutical Ingredient)

Acetazolamide API (Active Pharmaceutical Ingredient) refers to the pure chemical substance, acetazolamide, which serves as the core therapeutic component in pharmaceutical formulations. Here is a detailed overview:

1. Chemical Structure and Properties

• Chemical Name: N-(5-Sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide
• CAS Number: 59-66-5
• Molecular Formula: C₄H₆N₄O₃S₂
• Appearance: White crystalline powder, odorless, slightly bitter taste
• Solubility: Slightly soluble in boiling water, very slightly soluble in water or ethanol, practically insoluble in chloroform or ether; soluble in ammonia solution
• Melting Point: 256–261°C (decomposes upon melting)

2. Mechanism of Action

Acetazolamide is a potent carbonic anhydrase (CA) inhibitor, primarily targeting the CA-II and CA-IV isoforms. By inhibiting these enzymes, it reduces the conversion of carbon dioxide (CO₂) and water (H₂O) into bicarbonate (HCO₃⁻) and protons (H⁺). This leads to:

• Diuretic Effect: Decreased reabsorption of sodium (Na⁺), potassium (K⁺), and bicarbonate in the renal tubules, increasing urine output.
• Reduced Intraocular Pressure: Lowered aqueous humor production in the eye, beneficial in glaucoma treatment.
• Respiratory Alkalosis: Stimulation of ventilation, leading to increased elimination of CO₂ and respiratory alkalosis, which is useful in altitude sickness prevention.

3. Pharmacological Applications

• Glaucoma: Used to reduce intraocular pressure in open-angle and secondary glaucoma, and as an adjunct in acute angle-closure glaucoma before surgery.
• Edema: Manages edema due to congestive heart failure, though it is less potent than loop diuretics and often used in combination.
• Altitude Sickness: Prophylaxis and treatment of acute mountain sickness (AMS) by inducing metabolic acidosis and respiratory alkalosis.
• Epilepsy: Adjunctive therapy in certain types of seizures, particularly absence seizures.
• Other Uses: Management of idiopathic intracranial hypertension, periodic paralysis, and as a urine alkalinizer.

4. Pharmacokinetics

• Absorption: Well-absorbed orally, with peak plasma concentrations reached within 1–4 hours.
• Distribution: High protein binding (~90%).
• Metabolism: Minimal hepatic metabolism; excreted unchanged in the urine.
• Elimination Half-Life: Approximately 2–4 hours (short-acting); extended-release formulations have a longer duration of action.

5. Regulatory and Quality Considerations

• GMP Compliance: Manufactured under Good Manufacturing Practice (GMP) guidelines to ensure purity, potency, and safety.
• Impurity Control: Strict limits on impurities such as residual solvents, heavy metals, and degradation products.
• Stability: Must maintain potency under specified storage conditions (typically protected from light and moisture).

6. Market and Supply Chain

• Global Demand: Driven by its use in glaucoma, altitude sickness, and epilepsy, with steady growth in emerging markets.
• Key Producers: Concentrated in India, China, and Europe, with companies adhering to stringent regulatory standards (e.g., FDA, EMA, WHO).
• Formulations: Available as tablets, capsules, and injectables; extended-release formulations improve patient compliance.

7. Safety and Side Effects

• Common Adverse Effects: Paresthesia, metabolic acidosis, electrolyte imbalances (hypokalemia, hyponatremia), polyuria, and gastrointestinal disturbances.
• Contraindications: Hypersensitivity to sulfonamides, severe hepatic or renal impairment, hyperchloremic acidosis, and adrenal insufficiency.
• Monitoring: Regular assessment of electrolytes, renal function, and acid-base balance during prolonged therapy.