1. Basic properties of HPMC
Hydroxypropyl methylcellulose, the English name is hydroxypropyl methylcellulose, also known as HPMC. Its molecular formula is C8H15O8-(C10Hl8O6)N-C8HL5O8, and its molecular weight is approximately 86,000. The product is semi-synthetic, consisting of part methyl and part cellulose polyhydroxypropyl ether. It can be made by two methods: one is to treat the appropriate grade of methyl cellulose with NaOH, and then react with propylene oxide under high temperature and high pressure. The reaction time must be sustained so that the methyl and hydroxypropyl groups can be converted into ethers. The form exists and is bonded with the dehydrated glucose ring of cellulose to the required extent; the other is to treat cotton lint or wood pulp fiber with caustic soda to react to obtain methane chloride and propylene oxide, which can be further refined and ground. Make it into fine and uniform powder or granules. HPMC is a natural plant cellulose and an excellent pharmaceutical excipient with a wide range of sources. It is currently widely used at home and abroad and is one of the most commonly used pharmaceutical excipients in oral drugs.
This product is white to milky white, non-toxic, odorless, granular or fibrous, easy-flowing powder. Relatively stable under light and humidity. It expands in cold water to form a milky colloidal solution with a certain viscosity, and the sol-gel interconversion phenomenon occurs due to the temperature change of the solution with a certain concentration. Very soluble in 70% ethanol or dimethyl ketone, but insoluble in absolute ethanol, chloroform or ethoxyethane.
The pH value of hydroxypropyl methylcellulose is between 4.0 and 8.0, and it has good stability. The pH value is stable between 3.0 and 11.0. It can be stored at 20°C and relative humidity of 80% for 10 days. The moisture absorption coefficient of HPMC is 6.2%.
Hydroxypropyl methylcellulose has various types of products due to the different contents of methoxy and hydroxypropyl groups in the structure. At specific concentrations, various types of products have specific viscosity and thermal properties. Gel temperature and therefore have different properties that can be used for different purposes. Each country’s pharmacopoeia has different model requirements and expressions: the European Pharmacopoeia is based on the different viscosities, different degrees of substitution, usage levels and numbers of various grades of products sold on the market. The unit of the United States Pharmacopoeia is mPa·s, and the common names are as follows Use four digits to represent the content of hydroxypropyl methylcellulose with different substituents and types, such as hydroxypropyl methylcellulose, 2208. The first two digits represent the approximate percentage of methoxy groups, and the last two digits represent the hydroxyl group. Approximate percentage of propyl.
2. HPMC dissolved in water method
2.1 Hot water method
Since hydroxypropyl cellulose is insoluble in hot water, it can be evenly dispersed in hot water and then cooled. Two typical methods are introduced as follows:
(1) Put the required amount of hot water into the container and heat it to about 70°C. Add product gradually while stirring slowly. At first, the product floats on the water and then gradually forms a slurry.
(2) Add 1/3 or 2/3 of the required amount of water into the container and heat it to 70°C to disperse the product, prepare a hot water slurry, and then add the remaining amount of cold water or add ice water to the hot water slurry. slurry in water, stir the mixture after cooling.
2.2 Powder mixing method
The powder particles are thoroughly dispersed by dry blending with equal or greater amounts of other powdered ingredients and then dissolved with water, where the HMCS dissolves without coagulation.
3. Advantages of HPMC
3.1 Soluble in cold water
It is soluble in cold water below 40℃ or 70% ethanol, and basically insoluble in hot water above 60℃, but can gel.
3.2 Chemical inertness
HPMC is a non-ionic cellulose ether. Its solution has no ionic charge and does not interact with metal salts or ionic organic compounds. Therefore, other excipients do not react with it during the preparation production process.
3.3 Stability
It is stable to acid and alkali and can be stored for a long time between pH 3 and 1l without significant change in viscosity. Aqueous solutions of hydroxypropyl methylcellulose (HPMC) are antifungal and maintain good viscosity stability during long-term storage. The quality stability of HPMC is better than traditional excipients (such as dextrin, starch, etc.).
3.4 Adjustable viscosity
Different viscosity derivatives of HPMC can be in different proportions, and their viscosity can be changed according to needs to comply with certain rules and have a good linear relationship, so the ratio can be selected according to needs.
3.5 Metabolic inertness
HPMC is not absorbed or metabolized in the body and does not provide heat, so it is a safe excipient for pharmaceutical preparations.
3.6 Security
HPMC is generally considered a non-toxic, non-irritating material, with an LD50 of 5g/kg in mice and 5.2g/kg in rats. Daily doses are harmless to humans.
4 Application of HPMC in preparation
4.1 Film coating materials and film-forming materials
Hydroxypropyl methylcellulose (HPMC) is used as the film coating material. Its coated tablets have no obvious advantages over traditional coated tablets such as sugar-coated tablets in terms of masking the taste and appearance of the drug, but its hardness, brittleness, and hygroscopicity , poor disintegration. , coating weight gain and other quality indicators are better. The low viscosity grade of this product is used as a water-soluble film coating material for tablets and pills, and the high viscosity grade is used as a film coating material for organic solvent systems. The concentration is usually 2.0%~20%.
4.2 As a binder and disintegrant
The low viscosity grade of this product can be used as a binder and disintegrant for tablets, pills, and granules, while the high viscosity grade can only be used as a binder. The dosage varies according to the model and requirements, generally 5% for dry granulation tablets and 2% for wet granulation tablets.
4.3 As a suspension aid
The suspending agent is a viscous gel substance that is hydrophilic and can be used to slow down the settling speed of particles and adhere to the surface of the particles to prevent the particles from aggregating into balls. Suspension aids play an important role in the production of suspension agents. HPMC is an excellent suspension additive. Its dissolved colloidal solution can reduce the liquid-solid interfacial tension and the free energy of small solid particles, thereby enhancing the stability of the heterogeneous dispersion system. This product is a high-viscosity suspension preparation with good suspension effect, easy dispersion, non-stick wall, and fine flocculation particles. Its usual dosage is 0.5% to 1.5%.
4.4 As a retardant, sustained-release agent and porogen
The high viscosity grade of this product is used to prepare hydrophilic gel matrix sustained-release tablets, mixed material matrix sustained-release tablets of retarders and controlled-release agents. It has the effect of delaying drug release. Its usage concentration is 10%-80% ( W/W). Low viscosity levels are used as pore inducers in sustained or controlled release formulations. Such tablets can quickly achieve the initial dose required for therapeutic effect, then produce a sustained or controlled release effect, and maintain effective blood drug concentrations in the body. Hydroxypropyl methylcellulose hydrates in water to form a gel layer. The drug release mechanism of matrix tablets mainly includes the diffusion of the gel layer and the dissolution of the gel layer.
4.5 Thickeners and protective colloids
When this product is used as a thickener, the commonly used concentration is 0.45%~1.0%. This product can also increase the stability of hydrophobic glue, form a protective colloid, prevent particles from agglomeration and agglomeration, thereby inhibiting the formation of precipitation. Its common concentration is 0.5%~1.5%.
4.6 Use as capsule material
Usually the capsule shell material of capsules is gelatin. The production process of gelatin capsule shells is simple, but there are problems and phenomena such as poor protection against moisture- and oxygen-sensitive drugs, reduced drug dissolution, and delayed disintegration of capsule shells during storage. Therefore, hydroxypropyl methylcellulose is used as a substitute for capsule materials in the preparation of capsules, which improves the manufacturing, molding and use effects of capsules, and has been widely promoted at home and abroad.
4.7 As a bioadhesive
Bioadhesion technology uses excipients with bioadhesive polymers to adhere to biological mucosa and enhance the consistency and tightness of contact between the preparation and the mucosa, allowing the drug to be slowly released and absorbed by the mucosa to achieve therapeutic purposes. To achieve the purpose of treatment, it is currently widely used to treat diseases in the nasal cavity, oral mucosa and other parts of the body. Gastrointestinal bioadhesion technology is a new type of drug delivery system developed in recent years. It not only prolongs the residence time of drug preparations in the gastrointestinal tract, but also improves the contact performance between the drug and the cell membrane absorption site and changes the structure of the cell membrane. Mobility, that is, the permeability of the drug to the intestinal epithelial cells, thereby
Post time: Feb-01-2024