1. The basic properties of HPMC
Hypromellose, full name hydroxypropyl methylcellulose, alias HPMC. Its molecular formula is C8H15O8-(C10Hl8O6)n-C8Hl5O8, and its molecular weight is about 86000. This product is a semi-synthetic material, which is part of methyl and part of polyhydroxypropyl ether of cellulose. It can be produced by two methods: one is that the appropriate grade of methyl cellulose is treated with NaOH, and then reacted with propylene oxide under high temperature and pressure. The form is connected to the anhydroglucose ring of cellulose, and can reach the ideal level; the other is to treat cotton linter or wood pulp fiber with caustic soda, and react with methyl chloride and propylene oxide successively to obtain it, and then further refine , crushed to make fine and uniform powder or granules. HPMC is a variety of natural plant cellulose, and it is also an excellent pharmaceutical excipient, which has a wide range of sources. At present, it is widely used at home and abroad, and it is one of the pharmaceutical excipients with the highest utilization rate in oral drugs.
This product is white to milky white in color, non-toxic and tasteless, and is in the form of granular or fibrous powder that flows easily. It is relatively stable under light exposure and humidity. It swells in cold water to form a milky white colloidal solution, which has a certain degree of viscosity, and the phenomenon of sol-gel interconversion can occur due to the temperature change of a certain concentration of the solution. It is very soluble in 70% alcohol or dimethyl ketone, and will not dissolve in absolute alcohol, chloroform or ethoxyethane.
When the pH of hypromellose is between 4.0 and 8.0, it has good stability, and it can exist stably when the pH is between 3.0 and 11.0. When the temperature is 20°C and the relative humidity is 80%, it is stored for 10 days. The moisture absorption coefficient of HPMC is 6.2%.
Due to the different contents of methoxy and hydroxypropyl in the structure of hypromellose, various types of products have appeared. In specific concentrations, various types of products have specific viscosity and Thermal gelation temperatures, therefore, have different properties and can be used for different purposes. The pharmacopoeias of various countries have different regulations and representations on the models: the European Pharmacopoeia, according to the various grades of different viscosities and degrees of substitution of the products sold in the market, is represented by grades plus numbers, and the unit is mPa·s; in the United States Pharmacopoeia, the common name Add 4 digits at the end to indicate the content and type of each substituent of hypromellose, such as hypromellose 2208, the first two digits represent the approximate percentage of methoxy, and the last two digits represent hydroxypropyl Approximate percentage.
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 beginning, and then cooled. Two typical methods are described as follows:
(1) Put the required amount of hot water into the container, and heat it to about 70°C, gradually add this product under slow stirring, at the beginning, this product floats on the surface of the water, and then gradually forms a slurry, stirring Cool the slurry down.
(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, then add the remaining amount of cold water or ice water until the hot water silts In a slurry, the mixture is cooled after stirring.
2.2 Powder mixing method
The powder particles are fully dispersed by dry mixing with an equal or greater amount of other powdery ingredients, and then dissolved in water. At this time, the hypromellose can be dissolved without agglomeration.
3. Advantages of HPMC
3.1 Cold water solubility
Soluble in cold water below 40°C or 70% ethanol, basically insoluble in hot water above 60°C, but 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.
3.3 Stability
It is relatively stable to acid and alkali, and can be stored for a long time between pH 3 and 1l without obvious change in viscosity. The aqueous solution of hypromellose (HPMC) has anti-mildew effect and can maintain good viscosity stability during long-term storage. Pharmaceuticals using HPMC as excipients have better quality stability than those using traditional excipients (such as dextrin, starch, etc.).
3.4 Viscosity adjustability
Different viscosity derivatives of HPMC can be mixed according to different ratios, and its viscosity can change according to certain rules, and has a good linear relationship, so the ratio can be selected according to requirements.
3.5 Metabolic inertia
HPMC is not absorbed or metabolized in the body, and does not provide heat, so it is a safe pharmaceutical preparation excipient.
3.6 Security
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. Daily doses are harmless to humans.
4. Application of HPMC in preparation
4.1 As film coating material and film-forming material
Using hypromellose (HPMC) 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 of medicine 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 concentration is usually 2.0% to 20%.
4.2 As 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 dosage of binder for dry granulation tablets is 5%, and the dosage of binder for wet granulation tablets is 2%.
4.3 As a suspending agent
The suspending agent is a viscous gel substance with hydrophilicity, which can slow down the sedimentation speed of the particles when used in the suspending agent, and it can be attached to the surface of the particles to prevent the particles from aggregating and shrinking into a ball. Suspending agents play a vital role in making suspensions. HPMC is an excellent variety of suspending agents, and its dissolved colloidal solution can reduce the tension of the liquid-solid interface and the free energy on small solid particles, thereby enhancing the stability of the heterogeneous dispersion system. The high-viscosity grade of this product is used as a suspension-type liquid preparation prepared as a suspending agent. It has a good suspending effect, is easy to redisperse, does not stick to the wall, and has fine flocculated particles. The usual dosage is 0.5% to 1.5%.
4.4 As a blocker, sustained-release agent and pore-causing agent
The high-viscosity grade of this product is used to prepare hydrophilic gel matrix sustained-release tablets, blockers and controlled-release agents for mixed material matrix sustained-release tablets, and has the effect of delaying drug release. Its use concentration is 10%~80% (W /W). Low-viscosity grades are used as pore-forming agents for sustained-release or controlled-release preparations. The initial dose required for the therapeutic effect of this type of tablet can be achieved quickly, and then exert a sustained-release or controlled-release effect, and the effective blood drug concentration is maintained in the body . When hypromellose meets water, it hydrates to form a gel layer. The mechanism of drug release from the matrix tablet mainly includes the diffusion of the gel layer and the erosion of the gel layer.
4.5 Protective glue as thickener and colloid
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 agglomerating and agglomerating, thereby inhibiting the formation of sediment, and its usual concentration is 0.5%~1.5%.
4.6 Capsule material for capsules
Usually the capsule shell capsule material of capsule is based on gelatin. The production process of the gelatin capsule shell is simple, but there are some problems and phenomena such as poor protection against moisture and oxygen sensitive drugs, low drug dissolution rate, and delayed disintegration of the capsule shell during storage. Therefore, hypromellose, as a substitute for gelatin capsules, is used in the preparation of capsules, which improves the formability and use effect of capsules, and has been widely promoted at home and abroad.
4.7 as bioadhesive
Bioadhesion technology, the use of excipients with bioadhesive polymers, through adhesion to the biological mucosa, enhances 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 therapeutic purposes. It is currently widely used It is used to treat diseases of the nasal cavity, oral mucosa and other parts. Gastrointestinal bioadhesion technology is a new drug delivery system developed in recent years. It not only prolongs the residence time of pharmaceutical preparations in the gastrointestinal tract, but also improves the contact performance between the drug and the cell membrane at the absorption site, changing the fluidity of the cell membrane, Enhance the penetration of the drug to the intestinal epithelial cells, thereby improving the bioavailability of the drug.
4.8 As 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. direction.
Post time: Dec-15-2022