---

Pharmaceutical-grade Calcium Carbonate (CaCO₃) is a cornerstone material in modern drug formulation, serving dual critical roles as both an active pharmaceutical ingredient (API) and a versatile, multi-functional excipient. Unlike its industrial counterparts, pharmaceutical-grade CaCO₃ is manufactured and tested to meet the stringent purity, consistency, and safety standards mandated by global pharmacopoeias (USP, Ph. Eur., JP, ChP). Its unique physicochemical properties—including high purity, controlled particle size distribution, excellent compressibility, and chemical reactivity—make it indispensable in the development and production of solid oral dosage forms, antacid therapies, and phosphate-binding medications.

Product Specifications (Pharmaceutical Grade)‌

Item Specification ‌Product Name‌ Calcium Carbonate, Pharmaceutical Grade ‌INCI Name‌ Calcium Carbonate ‌Chemical Formula‌ CaCO₃ ‌Molecular Weight‌ 100.09 g/mol ‌CAS Number‌ 471-34-1 (Precipitated) ‌Appearance‌ Fine, white, odorless, crystalline powder. ‌Identification‌ Complies with USP/Ph. Eur. identification tests (reaction with acids, precipitation as calcium oxalate). ‌Assay (on dried basis)‌ 98.0% - 100.5% (as CaCO₃) ‌Loss on Drying‌ ≤ 2.0% (105°C to constant weight) ‌Acid-Insoluble Substances‌ ≤ 0.2% ‌Heavy Metals‌ ≤ 0.001% (10 ppm) ‌Arsenic (As)‌ ≤ 3 ppm ‌Lead (Pb)‌ ≤ 3 ppm ‌Microbial Limits‌ Total Aerobic Microbial Count (TAMC): ≤ 1000 CFU/g  Total Combined Yeasts & Molds Count (TYMC): ≤ 100 CFU/g  Absence of Escherichia coli, Salmonella spp. ‌Particle Size Distribution (PSD)‌ Customizable (D50 typically 5-50 μm). Controlled PSD is critical for batch consistency, flow, and dissolution. ‌Bulk & Tapped Density‌ Defined ranges to ensure consistent tablet weight and compression behavior. ‌pH (5% suspension)‌ 8.0 - 10.0 ‌Shelf Life‌ 36 months minimum when stored in original, unopened containers under recommended conditions. ‌Storage‌ Store in well-closed containers, in a cool, dry place (15-25°C), protected from moisture and acidic fumes.

Key Roles in Pharmaceutical Formulations‌

1. As an Active Pharmaceutical Ingredient (API)‌

Antacid:‌ Calcium carbonate neutralizes gastric acid (HCl) rapidly and effectively, providing relief from heartburn, acid indigestion, and dyspepsia. Its high acid-neutralizing capacity (ANC) and rapid onset of action make it a first-line OTC medication.
Calcium Supplement:‌ It is the most common and cost-effective source of elemental calcium (~40% by weight) for the prevention and treatment of calcium deficiency and osteoporosis. It is often combined with Vitamin D to enhance calcium absorption.
Phosphate Binder:‌ In patients with chronic kidney disease (CKD), it binds dietary phosphate in the gut, reducing serum phosphate levels and helping to manage renal osteodystrophy.

2. As a Critical Excipient‌

Diluent/Filler:‌ Its primary function in tablet and capsule formulation. It adds bulk to a formulation to achieve a practical tablet size for handling and compression.
Disintegrant (in certain forms):‌ While not a superdisintegrant, its effervescent reaction with gastric acid can aid in the initial breakdown of a tablet.
Alkalizing Agent:‌ Used to adjust the pH of formulations to improve stability or modify drug release.
Opacifying Agent:‌ In film coatings to provide an opaque, white background.
Source of Calcium Ions:‌ In effervescent formulations where it reacts with acids to produce carbon dioxide.

Critical Quality Attributes (CQAs) for Pharmaceutical Use‌

The functionality of calcium carbonate in a drug product is highly dependent on its physical and chemical properties, which must be tightly controlled:

Purity & Impurity Profile:‌ Stringent limits on heavy metals, arsenic, and acid-insoluble substances are non-negotiable for patient safety.
Particle Size & Distribution (PSD):‌ PSD directly affects ‌flowability, blend uniformity, compressibility, dissolution rate, and bioavailability‌. Fine particles may improve dissolution but hinder flow. A controlled, narrow PSD is essential for robust manufacturing.
Surface Area & Porosity:‌ Influence compaction behavior, binding properties, and chemical reactivity (e.g., acid-neutralizing speed).
Bulk Density:‌ Impacts die filling consistency and final tablet weight.
Compressibility:‌ Must provide adequate "binding" properties to form a mechanically strong tablet without excessive force.

Formulation Considerations & Challenges‌

Compatibility:‌ Generally inert, but can be incompatible with APIs that are sensitive to alkaline pH or that can form complexes with calcium ions (e.g., tetracycline antibiotics). Pre-formulation compatibility studies are essential.
Lubrication:‌ Has mild inherent lubricating properties but typically requires the addition of a lubricant (e.g., magnesium stearate) for high-speed tableting.
Dissolution for API Function:‌ As an antacid or calcium supplement, its dissolution profile in simulated gastric fluid is a key performance indicator. The use of highly reactive precipitated grades or micronized forms can optimize this.
Moisture Sensitivity:‌ Although stable, it should be protected from prolonged exposure to high humidity to prevent caking and flow issues.

Manufacturing & Sourcing: GCC vs. PCC‌

Ground Calcium Carbonate (GCC):‌ Milled from natural limestone or marble. May have more variable impurity profiles and broader PSD. Cost-effective for some standard applications.
Precipitated Calcium Carbonate (PCC):‌ Synthesized via a controlled chemical process. ‌This is the preferred grade for most critical pharmaceutical applications.‌ It offers:
Higher and more consistent purity.‌
Precise control over particle morphology (e.g., scalenohedral, rhombohedral), size, and surface area.‌
Better batch-to-batch reproducibility‌, which is paramount for regulatory filings (e.g., ANDA, NDA) and continuous manufacturing.

Regulatory & Compliance‌

Pharmaceutical-grade Calcium Carbonate must comply with the relevant monograph of the target market's pharmacopoeia. A comprehensive ‌Drug Master File (DMF)‌ or ‌Certificate of Suitability (CEP)‌ from the supplier is crucial for regulatory submissions, as it provides the regulatory agency with confidential details on the manufacturing, quality, and controls of the material.

Why Partner with a Specialized Pharmaceutical Supplier?‌

Sourcing is not a commodity purchase. A supplier dedicated to the pharmaceutical industry provides:

• ICH Q7 GMP Compliance:‌ Manufactured in facilities adhering to current Good Manufacturing Practices.
• Comprehensive Dossier Support:‌ Availability of DMF/CEP, Type II ASMF.
• Extensive Characterization Data:‌ Full suite of CQA data (PSD, BET surface area, density, etc.).
• Strict Change Control & Notification:‌ Guarantees supply consistency.
• Technical Expertise:‌ Support in formulation development and troubleshooting.

Looking for a reliable partner for your pharmaceutical-grade Calcium Carbonate?‌ Our portfolio includes both standard and customized PCC grades, backed by full regulatory documentation and dedicated technical support to ensure your formulation's success from development to commercial scale.