1. The basic nature of HPMC
Hypromellose, English name hydroxypropyl methylcellulose, alias HPMC. Its molecular formula is C8H15O8-(C10Hl8O6)n-C8Hl5O8, and the molecular weight is about 86,000. This product is a semi-synthetic material, which is part of the methyl group and part of the polyhydroxypropyl ether of cellulose. It can be manufactured by two methods: one is to treat the methyl cellulose of suitable grade with NaOH, and then react with propylene oxide under high temperature and high pressure. The reaction time must be sustained to allow the methyl and hydroxypropyl groups to bond with ether. The form of is connected to the anhydroglucose ring of cellulose, and can reach the desired degree; the other is to treat cotton linter or wood pulp fiber with caustic soda, and then obtain by reacting with chlorinated methane and propylene oxide successively, and then further refined , Pulverize, make into fine and uniform powder or granule. HPMC is a variety of natural plant cellulose, and it is also an excellent pharmaceutical excipient, which has a broad source. At present, it is widely used at home and abroad, and it is one of the pharmaceutical excipients with the highest utilization rate among oral drugs.
The color of this product is white to milky white, non-toxic and tasteless, and it is a granular or fibrous, easy-flowing powder. It is relatively stable under light exposure and humidity. It swells in cold water to form a milky white colloidal solution with a certain degree of viscosity. The sol-gel interconversion phenomenon can occur due to the temperature change of a certain concentration of solution. It is very easy to dissolve in 70% alcohol or dimethyl ketone, and will not dissolve in anhydrous alcohol, chloroform or ethoxyethane.
Hypromellose has good stability when the pH is between 4.0 and 8.0, and it can exist stably between 3.0 and 11.0. After storing for 10 days at a temperature of 20°C and a relative humidity of 80%, The moisture absorption coefficient of HPMC is 6.2%.
Due to the difference in the content of the two substituents in the structure of hypromellose, methoxy and hydroxypropyl, various types of products have appeared. In a specific concentration, various types of products have specific viscosity and Thermal gelation temperature, therefore, has different properties and can be used for different purposes. The pharmacopoeias of various countries have different specifications and expressions for the model: The European Pharmacopoeia is based on the various grades of the different viscosities and different degrees of substitution of the products on the market. It is expressed by the grade plus a number. The unit is mPa•s. After adding 4 digits to indicate the content and type of each substituent of hypromellose, for example, hypromellose 2208, the first two digits represent the approximate percentage of methoxy group, the last two digits represent hydroxypropyl Approximate percentage of cases.
2.The method of dissolving HPMC in water
2.1 Hot water method
Since hypromellose does not dissolve in hot water, it can be uniformly dispersed in hot water at the initial stage, and then when it is cooled, two typical methods are described as follows:
(1) Put the required amount of hot water in the container and heat it to about 70℃. Gradually add the product under slow stirring. At the beginning, the product floats on the surface of the water, and then gradually forms a slurry. Cool down the 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 to prepare a hot water slurry, and then add the remaining amount of cold water or ice water to the hot water slurry In the slurry, cool the mixture after stirring.
2.2 Powder mixing method
The powder particles and other powdery ingredients of equal or larger amount are fully dispersed by dry mixing, and then water is added to dissolve. At this time, the hypromellose can be dissolved without agglomeration.
3. Advantages of HPMC
3.1 Cold water solubility
It is soluble in cold water below 40°C or 70% ethanol. It is basically insoluble in hot water above 60°C, but it can be gelled.
3.2 Chemical inertness
Hypromellose (HPMC) is a kind of 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 process.
It is relatively stable to both acid and alkali, and can be stored for a long time between pH 3 to 1l, and its viscosity has no obvious change. The aqueous solution of hypromellose (HPMC) has an anti-mold effect and can maintain good viscosity stability during long-term storage. The pharmaceutical excipients using HPMC have better quality stability than those using traditional excipients (such as dextrin, starch, etc.).
3.4 Adjustability of viscosity
Different viscosity derivatives of HPMC can be mixed in different proportions, and its viscosity can change according to a certain rule, and has a good linear relationship, so it can be selected according to the requirements.
3.5 Metabolic inertia
HPMC is not absorbed or metabolized in the body, and does not provide calories, so it is a safe excipient for medicinal preparations.
It is generally believed that HPMC is a non-toxic and non-irritating material. The median lethal dose for mice is 5g/kg, and the median lethal dose for rats is 5.2g/kg. The daily dosage is harmless to the human body.
4. Application of HPMC in preparations
4.1 Used as film coating material and film forming material
Hypromellose (HPMC) is used as the film-coated tablet material. Compared with traditional coated tablets such as sugar-coated tablets, the coated tablets have no obvious advantages in masking the taste and appearance, but their hardness and friability , Moisture absorption, 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 use 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, and the high-viscosity grade can only be used as a binder. The dosage varies with different models and requirements. Generally, the amount of binder used for dry granulation tablets is 5%, and the amount of binder used for wet granulation tablets is 2%.
4.3 As a suspending agent
Suspending agent is a viscous gel substance with hydrophilicity. The use of suspending agent in suspending agent can slow down the sedimentation speed of particles, and it can be attached to the surface of particles to prevent the particles from polymerizing and condensing into a mass. Suspending agents play a vital role in the production of suspensions. HPMC is an excellent variety of suspending agents. The colloidal solution dissolved into it can reduce the tension of the liquid-solid interface and the free energy on the small solid particles, thereby enhancing the stability of the heterogeneous dispersion system. This product is a high-viscosity suspension liquid preparation prepared as a suspending agent. It has good suspending effect, easy to redisperse, non-sticky, and fine flocculated particles. The usual amount is 0.5% to 1.5%.
4.4 Used as a blocker, slow and controlled release agent and pore-forming agent
The high-viscosity grade of this product is used to prepare hydrophilic gel matrix sustained-release tablets, retarders and controlled-release agents for mixed-material matrix sustained-release tablets. It has the effect of delaying drug release. Its use concentration is 10%~80% (W /W). The low viscosity grade is used as a pore-forming agent for sustained or controlled release formulations. The initial dose required for the therapeutic effect of this type of tablet can be quickly reached, and then the sustained or controlled release effect is exerted, and the effective blood drug concentration is maintained in the body . Hypromellose hydrates to form a gel layer when it meets with water. The mechanism of drug release from the matrix tablet is mainly the diffusion of the gel layer and the erosion of the gel layer.
4.5 Protective glue used as thickener and colloid
When this product is used as a thickener, the usual concentration is 0.45%~1.0%. This product can also increase the stability of the hydrophobic glue, form a protective colloid, prevent particle coalescence and agglomeration, thereby inhibiting the formation of sediments. Its usual concentration is 0.5%~1.5%.
4.6 Used as capsule material
Usually, the capsule shell material of the capsule is mainly gelatin. The production process of Ming capsule shell is simple, but there are some problems and phenomena such as poor protection of moisture and oxygen sensitive drugs, reduced drug dissolution, and delay of disintegration of the capsule shell during storage. Therefore, hypromellose is used as a substitute for the capsule material in the preparation of capsules, which improves the moldability and use effect of the capsule, and has been widely promoted at home and abroad.
4.7 As a bioadhesive
Bioadhesive technology, the application of excipients with bioadhesive polymers, by adhering to the biological mucosa, enhance the continuity and tightness of the contact between the preparation and the mucosa, so that the drug is slowly released and absorbed by the mucosa to achieve the purpose of treatment. It is widely used now It is used to treat diseases of the nasal cavity and oral mucosa. 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 of the drug with the cell membrane of the absorption site and changes the fluidity of the cell membrane. The penetrating power of the drug to the epithelial cells of the small intestine is enhanced, thereby improving the bioavailability of the drug.
4.8 As a topical gel
As an adhesive preparation for skin, gel has a series of advantages such as safety, beauty, easy cleaning, low cost, simple preparation process, and good compatibility with drugs. In recent years, it has received extensive attention and has become the development of skin external preparations. direction.
4.9 As a precipitation inhibitor in the emulsification system
Post time: Dec-16-2021