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Send EmailCaffeine, Caffeine Anhydrous, Guaranine, Hycomine, Theine, Methyltheobromine, 58-08-2
CAFFEINE ANHYDROUS
1. Chemical Identity and Material Classification
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Chemical Name: Caffeine, 1,3,7-Trimethylxanthine, 3,7-Dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
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Synonyms: Anhydrous Caffeine, Coffeine, Guaranine, Theine, Methyltheobromine, Hycomine
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CAS Number: 58-08-2
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EC Number (EINECS): 200-362-1
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Molecular Formula: C₈H₁₀N₄O₂
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Molecular Weight: 194.19 g/mol
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Chemical Class: Methylxanthine alkaloid
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HS Code / GTIP: 2939.30.00.00
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Pharmacopeia Compliance: Ph. Eur., BP, USP
2. Physical Properties
2.1 General Physical Properties
| Property | Value |
|---|---|
| Appearance | White crystalline powder or silky, white glistening needles |
| Odor | Odorless |
| Density (18°C) | 1.23 g/cm³ |
| Bulk density | 220 kg/m³ |
| Melting point | 234–239°C |
| Boiling point | 178°C (sublimes) |
| Flash point | 93°C |
| Autoignition temperature | >600°C |
| pH (10 g/L solution, 20°C) | 5.5–6.5 |
| Dissociation constant (pKa, 40°C) | 10.4 |
| Shelf life | 48 months (under proper storage) |
2.2 Solubility in Water
| Temperature | Solubility |
|---|---|
| 20°C | 20–21.6 g/L (2 g/100 mL) |
| 16°C | 18.7 g/L |
| 100°C (boiling water) | 66 g/100 mL (very soluble) |
2.3 Solubility in Organic Solvents
| Solvent | Solubility |
|---|---|
| Ethanol (750 g/L) | Soluble in 100 parts |
| Diethyl ether | Slightly soluble |
| Chloroform | Slightly soluble |
| Acetone | Soluble |
| Dichloromethane | Soluble |
2.4 Partition Coefficient (log P)
| Temperature | Value |
|---|---|
| 23°C | -0.091 |
3. Chemical Properties
3.1 Molecular Structure
Structure: 1,3,7-Trimethylxanthine (purine derivative)
Caffeine is formed by the substitution of hydrogen atoms at positions 1, 3, and 7 of the xanthine (2,6-dioxopurine) ring with methyl groups.
3.2 Chemical Stability
| Parameter | Value |
|---|---|
| Chemical stability | Stable under normal temperatures and pressures |
| Polymerization hazard | Will not occur |
| Hygroscopicity | Low (anhydrous form is stable in air) |
| Light sensitivity | Slightly light-sensitive |
3.3 Incompatibilities
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Strong oxidizing agents (fire/explosion risk)
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May release toxic gases upon contact with acids
3.4 Hazardous Decomposition Products
| Product | Description |
|---|---|
| Carbon oxides (CO, CO₂) | Combustion/decomposition product |
| Nitrogen oxides (NO, NO₂, etc.) | Combustion/decomposition product |
4. Quality Specifications (Pharmacopeial Grades)
4.1 Pharmacopeia Requirements (Ph. Eur., BP, USP)
| Parameter | Specification |
|---|---|
| Assay (on dried substance) | 98.5–101.0% |
| Loss on drying (80°C) | ≤ 0.5% |
| Sulfated ash | ≤ 0.1% |
| Sulfates (SO₄) | ≤ 500 ppm |
| Heavy metals (as Pb) | ≤ 0.001% |
| Clarity and color of solution | Clear and colorless |
| Identification (IR) | Conforms to reference spectrum |
| Melting point | 234–239°C |
| pH (10 g/L) | 5.5–6.5 |
4.2 USP/EP Grade Additional Specifications
| Parameter | Specification |
|---|---|
| Acidity | Conforms |
| Unspecified impurities | ≤ 0.10% |
| Total impurities | ≤ 0.10% |
| Organic impurities (HPLC) | Conforms to pharmacopeia limits |
5. Pharmacological and Biological Properties
5.1 Mechanism of Action
| Mechanism | Description |
|---|---|
| Adenosine receptor antagonist | CNS stimulant effect, psychotropic effect |
| Phosphodiesterase inhibition | Increased cAMP, cardiac stimulation |
| Adenosine receptor antagonist (low dose) | Wakefulness, fatigue reduction |
5.2 Pharmacological Effects
| Effect | Description |
|---|---|
| CNS stimulant | Cerebral cortex → medulla → spinal cord |
| Cardiac stimulation | Positive inotropic effect |
| Vasoconstriction (cerebral) | Anti-migraine effect |
| Vasodilation (peripheral) | Balances blood pressure effects, reduces arterial resistance |
| Skeletal muscle stimulation | Increased muscle performance |
| Respiratory stimulant | Stimulates respiratory center |
| Diuretic | Increases urine excretion |
| Gastric acid secretion | Increases |
5.3 Dosage Information
| Route | Dose | Application |
|---|---|---|
| Oral (asthenia treatment) | 50–100 mg / 6 hours | Up to 1200 mg/day based on clinical response |
| Oral (analgesic combination) | 30–65 mg | With aspirin, paracetamol, or codeine |
| Topical (cosmetic) | Up to 30% | Magistral formulation in atopic dermatitis treatment |
| Adult daily maximum | ~300 mg | General safety recommendation |
| Acute LD₅₀ (oral, rat) | 367.7 mg/kg | Acute toxicity threshold |
6. Natural Sources
Caffeine occurs naturally in approximately 60 plant species, including:
| Source | Approximate Caffeine Content |
|---|---|
| Coffee beans | 1–2% |
| Tea leaves | 2–4% |
| Guarana | 3–6% |
| Cocoa beans | 0.1–0.5% |
| Mate leaves | 0.5–1.5% |
7. Industrial Applications
7.1 Pharmaceutical Applications (Primary Application)
| Application | Description | Typical Use |
|---|---|---|
| Headache and migraine | Adjuvant component in analgesic formulations | 30–65 mg/dose |
| Cold preparations | Stimulant in combination products | 30–50 mg/dose |
| Asthenia and mental fatigue | CNS stimulant | 50–100 mg / 6 hours |
| Narcolepsy | Adjunct treatment | 100–200 mg/day |
| Heart failure | Cardiac stimulation | Physician-directed |
| Bronchial asthma | Respiratory stimulant effect | Physician-directed |
| Resuscitation solutions | Respiratory stimulant | Emergency medical use |
7.2 Food and Beverage Applications
| Application | Description | Typical Concentration |
|---|---|---|
| Energy drinks | Performance enhancer, stimulant | 30–50 mg/100 mL |
| Carbonated soft drinks (cola) | Flavor, stimulant effect | 10–25 mg/100 mL |
| Energy shots | High-concentration stimulant | 200–300 mg/dose |
| Multivitamin supplements | Energy-boosting component | Variable |
| Sports nutrition (pre-workout) | Performance enhancer | 150–300 mg/dose |
Food additive approvals:
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USA: GRAS (Generally Recognized as Safe)
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EU: Permitted as food additive
7.3 Cosmetic and Personal Care Applications
| Application | Description | Typical Concentration |
|---|---|---|
| Eye creams | Puffiness reduction, antioxidant | 1–5% |
| Anti-cellulite creams | Lipolysis stimulator (phosphodiesterase inhibition) | 1–10% |
| Body lotions | Skin conditioning agent | 0.5–5% |
| Facial creams | Antioxidant, skin protectant | 0.5–2% |
| Hair care products | Stimulant effect (rare) | 0.1–1% |
INCI Name: Caffeine
7.4 Sports Nutrition Applications
| Application | Description | Typical Dose |
|---|---|---|
| Pre-workout supplements | Energy, focus, performance enhancement | 150–300 mg |
| Fat burner formulations | Metabolism booster, lipolysis activator | 100–200 mg |
| Endurance supplements | Stamina enhancement | 100–300 mg |
| Concentration and focus products | Wakefulness and mental performance | 50–200 mg |
7.5 Industrial Applications
| Application | Description |
|---|---|
| Pesticide / pest repellent | Natural insect-paralyzing properties |
| Breath freshener sprays | Component in spray formulations |
8. Toxicology and Safety
8.1 Acute Toxicity
| Parameter | Value | Classification |
|---|---|---|
| Oral LD₅₀ (rat) | 367.7 mg/kg (female/male) | Acute Tox. 4 (H302) |
| Oral LD₅₀ (rat) | 261–383 mg/kg | Acute Tox. 4 (H302) |
| Dermal LD₅₀ (rat) | >2,000 mg/kg | Not classified |
| Inhalation LC₅₀ (rat, 4 hours) | 4.94 mg/L | Acute Tox. 4 (H332) |
8.2 Chronic Toxicity and Carcinogenicity
| Endpoint | Classification |
|---|---|
| Carcinogenicity (IARC) | Group 3 – Not classifiable as to carcinogenicity in humans |
| NTP | Not listed |
| OSHA Ca | Not listed |
| Mutagenicity | Negative in animal studies |
| Reproductive toxicity | Not classified |
| Skin irritation | Non-irritant (rabbit) |
| Eye irritation | Non-irritant (rabbit) |
| Skin sensitization | Non-sensitizer |
8.3 Human Health Effects (High Dose)
| Effect | Description |
|---|---|
| Cardiovascular | Increased blood pressure, palpitations |
| Gastrointestinal | Heartburn, increased gastric acid secretion |
| CNS | Anxiety, insomnia, restlessness, tremor |
| Metabolic | Increased diuresis |
| Dependence | Habit-forming effect (tolerance may develop) |
| Liver | Irregularities – human evidence |
8.4 GHS Classification
| Classification | Category |
|---|---|
| Signal word | Warning |
| Hazard statements | H302 – Harmful if swallowed |
| Precautionary statements | P264, P270, P301+P312, P330, P501 |
8.5 NFPA Rating
| Health | Flammability | Reactivity |
|---|---|---|
| 1-2 | 0-1 | 0 |
9. Safety Precautions and Personal Protective Equipment (PPE)
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Hazards:
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Harmful if swallowed (H302)
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Dust may cause respiratory tract irritation
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May be combustible at high temperatures (dust explosion risk)
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Mild irritant upon eye contact
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PPE (recommended – industrial handling):
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Dust mask (FFP2/N95) – for dusty operations
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Safety glasses (EN 166) – side shields
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Chemical-resistant gloves (nitrile)
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Protective clothing (dust protection)
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Engineering controls:
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Local exhaust ventilation (LEV) for dust control
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Dust collection systems
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Eyewash stations
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Storage conditions:
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Cool, dry, well-ventilated area (15–25°C recommended, do not exceed 30°C)
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Keep tightly closed in original container
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Protect from moisture
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Keep away from heat sources and ignition sources
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Store away from strong oxidizing agents
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First aid:
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Inhalation: Remove to fresh air; artificial respiration may be necessary; consult a physician
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Skin contact: Wash with soap and plenty of water; consult a physician
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Eye contact: Rinse with water (as a precaution)
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Ingestion: Rinse mouth; never give anything by mouth to an unconscious person; consult a physician
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10. Environmental Fate
| Parameter | Value |
|---|---|
| Biodegradability | Fully biodegradable |
| Fish toxicity (LC₅₀, 96 hours) | 87 mg/L (Leuciscus idus) |
| Daphnia magna (EC₅₀, 48 hours) | 182 mg/L |
| Algae toxicity (EC₅₀, 72 hours) | >100 mg/L (Desmodesmus subspicatus) |
| Discharge to water bodies | Prevent entry into sewers |
11. Transport Information
| Regulation | Classification |
|---|---|
| UN Number | Not regulated (non-hazardous) |
| ADR/RID | Not classified as dangerous goods |
| IMDG | Not regulated |
| IATA | Not regulated |
| Proper shipping name | Caffeine (non-hazardous) |
| Transport restrictions | No special requirements for land, sea, or air transport |
12. Regulatory Status
| Regulation | Status |
|---|---|
| REACH (EC 1907/2006) | Registered |
| TSCA (US) | Listed |
| FDA | GRAS (Generally Recognized as Safe) – food and beverages |
| EU Food Additives | Permitted |
| Pharmacopeias | Ph. Eur., BP, USP |
| Cosmetics (EU) | Permitted (skin conditioning agent) |
| IARC | Group 3 – Not classifiable as to carcinogenicity in humans |
13. Synonyms and Common Names
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English: Caffeine, Caffeine Anhydrous, 1,3,7-Trimethylxanthine, Guaranine, Theine, Methyltheobromine
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Other names: 3,7-Dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
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Trade names: Coffeine, Hycomine
14. Why Choose Caffeine Anhydrous?
| Advantage | Description |
|---|---|
| High purity (98.5–101.0%) | Meets pharmacopeia standards; consistent quality |
| Long shelf life (48 months) | Excellent stability under proper storage |
| Versatile solubility | Soluble in both water and organic solvents – suitable for various formulations |
| Pharmacopeia approved | USP, Ph. Eur., BP – globally accepted |
| Well-characterized safety profile | Centuries of use; low acute toxicity (LD₅₀ 367 mg/kg) |
| Widely available | Produced globally by numerous suppliers |
| Naturally derived or synthetic | Both sources available (natural extraction or chemical synthesis) |
| Multiple formulation types | Tablets, capsules, liquids, powders, cosmetics, food, beverages |
Limitations:
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Limited water solubility (20 g/L at 20°C) – Requires hot water or propylene glycol for high-concentration solutions
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Crystallization risk at room temperature – May require solubility stabilization in high concentrations
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Habit-forming at high doses – Tolerance and dependence potential
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Individual sensitivity – Side effects vary significantly from person to person
15. Formulation Notes
15.1 Aqueous Solubility Stabilization
Due to caffeine's limited water solubility (20 g/L at 20°C), for high-concentration formulations:
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Propylene glycol (PG) addition increases solubility and prevents crystallization
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Hot water use (up to 66 g/100 mL)
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Solubilization with surfactants such as Polysorbate 80
15.2 Typical Solvent Compatibility
| Solvent | Compatibility |
|---|---|
| Water (20°C) | Limited (2 g/100 mL) |
| Water (100°C) | Good (66 g/100 mL) |
| Ethanol | Partially soluble |
| Propylene glycol | Good |
| Glycerin | Moderate |
| Polyethylene glycol (PEG) | Good |
16. Comparison with Other Stimulants
| Property | Caffeine | Theobromine | Theophylline |
|---|---|---|---|
| Methyl groups | 3 (1,3,7) | 2 (3,7) | 2 (1,3) |
| CNS stimulation | High | Low | Very high |
| Cardiac effect | Moderate | Low | High |
| Diuretic effect | Moderate | Low | High |
| Bronchodilation | Low | Low | High |
| Primary source | Coffee, tea | Cocoa | Tea |
| Oral LD₅₀ (rat) | ~367 mg/kg | ~1,000 mg/kg | ~200 mg/kg |
17. Frequently Asked Questions (FAQs)
Q1: What is the difference between caffeine anhydrous and caffeine monohydrate?
A1: Caffeine anhydrous contains no water. Caffeine monohydrate contains one molecule of water (8.5–15.0% loss on drying). The anhydrous form provides higher active concentration.
Q2: What is the safe daily caffeine intake?
A2: The typical recommendation for adults is a maximum of 300–400 mg per day. The LD₅₀ of 367 mg/kg indicates that acute toxicity occurs at very high doses (5-10 grams at once).
Q3: Is caffeine carcinogenic?
A3: No. IARC (International Agency for Research on Cancer) lists caffeine as Group 3 – Not classifiable as to its carcinogenicity to humans.
Q4: How do I dissolve caffeine in water?
A4: Caffeine dissolves at 20 g/L at 20°C. For higher concentrations, use boiling water (66 g/L at 100°C) or add propylene glycol.
18. Industrial Application Summary Table
| Sector | Application | Typical Concentration | Function |
|---|---|---|---|
| Pharmaceutical | Headache/analgesic | 30–65 mg/dose | Stimulant, vasoconstrictor |
| Pharmaceutical | Narcolepsy/asthenia | 50–200 mg/dose | CNS stimulant |
| Food | Energy drinks | 30–50 mg/100 mL | Stimulant |
| Food | Carbonated soft drinks | 10–25 mg/100 mL | Flavor, stimulant |
| Sports Nutrition | Pre-workout | 150–300 mg/dose | Performance enhancer |
| Cosmetics | Eye creams | 1–5% | Puffiness reduction, antioxidant |
| Cosmetics | Anti-cellulite | 1–10% | Lipolysis activator |
| Agriculture | Pesticide | Variable | Natural insect repellent |
19. Storage Notes
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Temperature: 15–30°C (controlled room temperature)
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Humidity: Dry environment
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Light: Slightly light-sensitive – store in opaque containers
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Container: Original, tightly closed containers
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Distinguishing features: Anhydrous form does not effloresce in air (monohydrate effloresces)
20. Summary Table – Key Specifications at a Glance
| Parameter | Value |
|---|---|
| Product Name | Caffeine Anhydrous |
| CAS Number | 58-08-2 |
| Molecular Formula | C₈H₁₀N₄O₂ |
| Molecular Weight | 194.19 g/mol |
| Appearance | White crystalline powder or silky crystals |
| Odor | Odorless |
| Density | 1.23 g/cm³ |
| Melting Point | 234–239°C |
| Boiling Point | 178°C (sublimes) |
| Flash Point | 93°C |
| pH (10 g/L) | 5.5–6.5 |
| Water Solubility (20°C) | 20 g/L |
| Water Solubility (100°C) | 66 g/100 mL |
| log P (23°C) | -0.091 |
| Assay (Pharmacopeia) | 98.5–101.0% |
| Shelf Life | 48 months |
| Primary Applications | Pharmaceuticals (CNS stimulant), food/beverage, cosmetics, sports nutrition |
| IARC Carcinogenicity | Group 3 (not classifiable) |
| Oral LD₅₀ (rat) | 367.7 mg/kg |
| GHS Signal Word | Warning |
| Hazard Statements | H302 (Harmful if swallowed) |
| UN Number | Not regulated |
This TDS is prepared in compliance with ISO 11014-1 format and is intended for pharmaceutical manufacturers, food and beverage formulators, cosmetic chemists, sports nutrition manufacturers, and procurement professionals. Certificates of Analysis (CoA), Safety Data Sheets (SDS), and sample validation reports are available upon request.
