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Hydroxypropyl methylcellulose, often abbreviated as HPMC, is a semisynthetic, inert, viscoelastic polymer commonly used as an excipient and controlled-delivery component in oral medicaments, as well as in various industrial applications.
Hydroxypropyl methylcellulose is a cellulose ether derived from cellulose by chemical modification, where some of the hydroxyl groups are substituted with methoxy and hydroxypropyl groups.
HPMC is water-soluble, non-ionic, and forms a clear, odorless, tasteless film.
Hydroxypropyl methylcellulose acts as a thickener, emulsifier, film former, binder, and stabilizer.
Hydroxypropyl methylcellulose is widely used in pharmaceuticals, cosmetics, food products, and construction materials.
CAS Number: 9004-65-3
Synonyms and Other Names
Hydroxypropyl methylcellulose,Hypromellose,HPMC,Methylhydroxypropyl cellulose,Cellulose, 2-hydroxypropyl methyl ether,Methocel (brand name),E464 (food additive code), Hydroxypropyl methyl ether of cellulose
Hydroxypropyl methylcellulose (HPMC), also known as hypromellose, is a semisynthetic, inert, viscoelastic polymer derived from cellulose.
It is a multifunctional compound widely utilized in pharmaceutical formulations, food products, cosmetic preparations, and construction materials.
Derived through the chemical modification of natural cellulose, HPMC inherits biocompatibility and biodegradability, which, along with its versatile physicochemical properties, render it a material of choice in many industrial applications.
This paper presents a detailed analysis of HPMC, covering its chemical characteristics, synthesis, industrial use, analytical methodologies, and future prospects.
Chemical Structure and Composition
HPMC is a cellulose ether composed of D-glucose units linked by β-(1→4)-glycosidic bonds.
The native cellulose is chemically modified by replacing some of the hydroxyl groups on the glucose rings with methoxy (-OCH3) and hydroxypropyl (-CH2CHOHCH3) groups.
The degree of substitution (DS) refers to the average number of hydroxyl groups replaced per anhydroglucose unit, while the molar substitution (MS) refers to the average number of hydroxypropyl groups attached per anhydroglucose unit.
These parameters determine the physical and chemical behavior of HPMC.
Molecular Formula: Variable depending on substitution
Typical DS (methoxy): 1.4–2.0MS (hydroxypropyl): 0.15–1.0
Physical and Chemical Properties
HPMC is an off-white to white powder that is odorless and tasteless.
It is soluble in cold water and forms a colloidal solution.
Its properties depend on the degree of substitution and molecular weight.
The aqueous solutions of HPMC exhibit non-Newtonian, pseudoplastic behavior, which is shear-thinning and highly desirable in various applications.
Appearance: White/off-white powder
Solubility: Soluble in cold water; forms gels or colloidal solutions
pH range (2% solution): 5.0–8.0
Viscosity: 5 to 100,000 mPa·s (depends on grade and concentration)
Moisture Content: <5%
Bulk Density: ~0.5 g/cm³
Grades and Classification
HPMC grades are generally classified based on viscosity and substitution levels. Commonly used naming conventions include:
E-Grade: Lower viscosity; high substitution
K-Grade: High viscosity; moderate substitution
F-Grade: Film-forming; food-grade
Each grade is selected based on the application requirements.
Pharmaceutical and food industries often demand specific grades certified by regulatory authorities.
Production Process
HPMC is synthesized through a three-step reaction process:
Alkalization: Purified cellulose is treated with sodium hydroxide to swell and activate the fibers.
Etherification: The swollen cellulose reacts with methyl chloride and propylene oxide to substitute methoxy and hydroxypropyl groups.
Neutralization and Purification: The product is neutralized, washed to remove impurities, dried, and milled.
The reaction parameters such as time, temperature, and concentration of reagents influence the final DS and MS values.
Characterization and Analytical Methods
Various analytical techniques are employed to characterize HPMC:
Fourier Transform Infrared Spectroscopy (FTIR): To confirm functional groups
Nuclear Magnetic Resonance (NMR): For detailed molecular structure
Gel Permeation Chromatography (GPC): To determine molecular weight
Thermogravimetric Analysis (TGA): For thermal stability
X-Ray Diffraction (XRD): To assess crystallinity
Viscometry and Rheometry: For flow and viscosity analysis
Solubility and Viscosity Behavior
HPMC is insoluble in hot water but dissolves in cold water to form a transparent, stable colloid.
Upon heating, aqueous solutions undergo reversible gelation.
The viscosity is highly dependent on concentration, temperature, and shear rate.
Gelation Temperature: 60–80°C
Shear-thinning Behavior: Useful in construction and pharmaceutical applications
Thermal Properties
HPMC demonstrates considerable thermal stability:
Glass Transition Temperature (Tg): ~180°C
Decomposition Temperature: Onset around 200°C
Thermal Degradation: Occurs in multiple stages; involves depolymerization and combustion
SAFETY INFORMATION ABOUT HYDROXYPROPYL METHYLCELLULOSE
First aid measures:
Description of first aid measures:
General advice:
Consult a physician.
Show this safety data sheet to the doctor in attendance.
Move out of dangerous area:
If inhaled:
If breathed in, move person into fresh air.
If not breathing, give artificial respiration.
Consult a physician.
In case of skin contact:
Take off contaminated clothing and shoes immediately.
Wash off with soap and plenty of water.
Consult a physician.
In case of eye contact:
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
Continue rinsing eyes during transport to hospital.
If swallowed:
Do NOT induce vomiting.
Never give anything by mouth to an unconscious person.
Rinse mouth with water.
Consult a physician.
Firefighting measures:
Extinguishing media:
Suitable extinguishing media:
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, Nitrogen oxides (NOx), Hydrogen chloride gas
Advice for firefighters:
Wear self-contained breathing apparatus for firefighting if necessary.
Accidental release measures:
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment.
Avoid breathing vapours, mist or gas.
Evacuate personnel to safe areas.
Environmental precautions:
Prevent further leakage or spillage if safe to do so.
Do not let product enter drains.
Discharge into the environment must be avoided.
Methods and materials for containment and cleaning up:
Soak up with inert absorbent material and dispose of as hazardous waste.
Keep in suitable, closed containers for disposal.
Handling and storage:
Precautions for safe handling:
Avoid inhalation of vapour or mist.
Conditions for safe storage, including any incompatibilities:
Keep container tightly closed in a dry and well-ventilated place.
Containers which are opened must be carefully resealed and kept upright to prevent leakage.
Storage class (TRGS 510): 8A: Combustible, corrosive hazardous materials
Exposure controls/personal protection:
Control parameters:
Components with workplace control parameters
Contains no substances with occupational exposure limit values.
Exposure controls:
Appropriate engineering controls:
Handle in accordance with good industrial hygiene and safety practice.
Wash hands before breaks and at the end of workday.
Personal protective equipment:
Eye/face protection:
Tightly fitting safety goggles.
Faceshield (8-inch minimum).
Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection:
Handle with gloves.
Gloves must be inspected prior to use.
Use proper glove
removal technique (without touching glove's outer surface) to avoid skin contact with this product.
Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
Full contact:
Material: Nitrile rubber
Minimum layer thickness: 0.11 mm
Break through time: 480 min
Material tested:Dermatril (KCL 740 / Aldrich Z677272, Size M)
Splash contact
Material: Nitrile rubber
Minimum layer thickness: 0.11 mm
Break through time: 480 min
Material tested:Dermatril (KCL 740 / Aldrich Z677272, Size M)
It should not be construed as offering an approval for any specific use scenario.
Body Protection:
Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection:
Where risk assessment shows air-purifying respirators are appropriate use a fullface respirator with multi-purpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls.
If the respirator is the sole means of protection, use a full-face supplied air respirator.
Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so.
Do not let product enter drains.
Discharge into the environment must be avoided.
Stability and reactivity:
Chemical stability:
Stable under recommended storage conditions.
Incompatible materials:
Strong oxidizing agents:
Hazardous decomposition products:
Hazardous decomposition products formed under fire conditions.
Carbon oxides, Nitrogen oxides (NOx), Hydrogen chloride gas.
Disposal considerations:
Waste treatment methods:
Product:
Offer surplus and non-recyclable solutions to a licensed disposal company.
Contact a licensed professional waste disposal service to dispose of this material.
Contaminated packaging:
Dispose of as unused product
