Pharmaceutical excipients are excipients and adjuvants used in the production of medicines and formulating prescriptions, and are an important part of pharmaceutical preparations. As a natural polymer derived material, cellulose ether has the characteristics of biodegradability, non-toxicity, and low price, such as sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, Cellulose ethers such as hydroxyethyl cellulose and ethyl cellulose have important application value in pharmaceutical excipients. At present, the products of most domestic cellulose ether enterprises are mainly used in the middle and low-end fields of the industry, and the added value is not high. The industry urgently needs to transform and upgrade and improve the high-end applications of products.
Pharmaceutical excipients play an important role in the development and production of formulations. For example, in sustained-release preparations, polymer materials such as cellulose ethers are used as pharmaceutical excipients in sustained-release pellets, various matrix sustained-release formulations, coated sustained-release formulations, sustained-release capsules, sustained-release drug films, and sustained-release resin drugs. Preparations and liquid sustained-release preparations have been widely used. In this system, polymers such as cellulose ethers are generally used as drug carriers to control the release rate of drugs in the human body, that is, they are required to be slowly released in the body at a set rate within a certain time range to achieve the purpose of effective treatment.
According to the statistics of Consulting and Research Department, there are about 500 kinds of excipients on the market in my country, but compared with the United States (more than 1500 kinds) and the European Union (more than 3000 kinds), there is a big difference, and the types are still small. my country’s pharmaceutical excipients The development potential of the market is huge. It is understood that the top ten pharmaceutical excipients in my country’s market scale are medicinal gelatin capsules, sucrose, starch, film coating powder, 1,2-propylene glycol, PVP, hydroxypropyl methylcellulose (HPMC), and microcrystalline fibers. Vegetarian, HPC, lactose.
“Natural cellulose ether is the general term for a series of cellulose derivatives produced by the reaction of alkali cellulose and etherifying agent under certain conditions, and is a product in which the hydroxyl groups on the cellulose macromolecule are partially or completely replaced by ether groups. Cellulose ethers are widely used in the fields of petroleum, building materials, coatings, food, medicine and daily chemicals. In all fields, pharmaceutical-grade products are basically in the middle and high-end areas of the industry and have high added value. Due to strict quality requirements, the production of pharmaceutical-grade cellulose ethers is also relatively difficult. It can be said that the quality of pharmaceutical-grade products can basically represent the technical strength of cellulose ether enterprises. Cellulose ether is usually added as a retarder, matrix material and thickener to make sustained-release matrix tablets, gastric-soluble coating materials, sustained-release microcapsule packaging materials, sustained-release drug film materials, etc.
Sodium carboxymethyl cellulose (CMC-Na) is the cellulose ether with the largest output and consumption at home and abroad. It is an ionic cellulose ether made from cotton and wood through alkalization and etherification with chloroacetic acid. CMC-Na is a commonly used pharmaceutical excipient. It is often used as a binder for solid preparations and as a thickening, thickening and suspending agent for liquid preparations. It can also be used as a water-soluble matrix and film-forming material. It is often used as a sustained-release drug film material and sustained-release matrix tablet in sustained (controlled) release formulations.
In addition to sodium carboxymethyl cellulose as pharmaceutical excipients, croscarmellose sodium can also be used as pharmaceutical excipients. Cross-linked carboxymethyl cellulose sodium (CCMC-Na) is a water-insoluble substance that carboxymethyl cellulose reacts with a cross-linking agent at a certain temperature (40-80°C) under the action of an inorganic acid catalyst and is purified. The crosslinking agent can be propylene glycol, succinic anhydride, maleic anhydride, adipic anhydride, and the like. Croscarmellose sodium is used as a disintegrant for tablets, capsules and granules in oral preparations. It relies on capillary and swelling effects to achieve disintegration. It has good compressibility and strong disintegration. Studies have shown that the swelling degree of croscarmellose sodium in water is greater than that of common disintegrants such as low-substituted sodium carboxymethyl cellulose and hydrated microcrystalline cellulose.
Methyl cellulose (MC) is a non-ionic cellulose monoether made from cotton and wood through alkalization and methyl chloride etherification. Methyl cellulose has excellent water solubility and is stable in the pH range of 2.0 to 13.0. It is widely used in pharmaceutical excipients, and is used in sublingual tablets, intramuscular injections, ophthalmic preparations, oral capsules, oral suspensions, oral tablets and topical preparations. In addition, in sustained-release formulations, MC can be used as a hydrophilic gel matrix sustained-release formulation, gastric-soluble coating material, sustained-release microcapsule packaging material, sustained-release drug film material, etc.
Hydroxypropyl methylcellulose (HPMC) is a non-ionic cellulose mixed ether made from cotton and wood through alkalization and etherification of propylene oxide and methyl chloride. It is odorless, tasteless, non-toxic, soluble in cold water, and gels in hot water. Hydroxypropyl methylcellulose is a cellulose mixed ether variety that has been rapidly increasing in production, consumption and quality in the past 15 years. It is also one of the largest pharmaceutical excipients used at home and abroad. It has been used as a pharmaceutical excipient for nearly 50 years. Years of history. At present, the application of HPMC is mainly reflected in the following five aspects:
One is as a binder and disintegrant. HPMC as a binder can make the drug easy to wet, and it can expand hundreds of times after absorbing water, so it can significantly improve the dissolution or release of the tablet. HPMC has strong viscosity, and can enhance the particle viscosity and improve the compressibility of raw materials with crisp or hard texture. HPMC with low viscosity can be used as a binder and disintegrant, and HPMC with high viscosity can only be used as a binder.
Secondly, it is used as a sustained and controlled release material for oral preparations. HPMC is a commonly used hydrogel matrix material in sustained-release preparations. HPMC of low viscosity grade (5～50mPa·s) can be used as a binder, viscosity increasing agent and suspending agent, and HPMC of high viscosity grade (4000～100000mPa·s) can be used to prepare mixed material matrix sustained-release tablets and sustained-release Blocker for capsules and hydrophilic gel matrix sustained-release tablets. HPMC is soluble in gastrointestinal fluid, has the advantages of good compressibility, good fluidity, strong drug loading capacity and drug release characteristics not affected by pH. It is an extremely important hydrophilic carrier material in sustained-release preparation systems and is often used as The hydrophilic gel matrix and coating material of sustained-release preparations, and used in gastric floating preparations and sustained-release drug membrane auxiliary materials.
The third is as a coating film-forming agent. HPMC has good film-forming properties. The film formed by it is uniform, transparent, and tough, and it is not easy to adhere during production. Especially for drugs that are easy to absorb moisture and are unstable, using it as an isolation layer can greatly improve the stability of the drug and prevent The film changes color. HPMC has a variety of viscosity specifications. If selected properly, the quality and appearance of the coated tablets are better than other materials, and its common concentration is 2% to 10%.
Four is used as a capsule material. In recent years, with the frequent outbreak of global animal epidemics, compared with gelatin capsules, plant capsules have become the new darling of the pharmaceutical and food industries. Pfizer has successfully extracted HPMC from natural plants and prepared VcapTM vegetable capsules. Compared with traditional gelatin hollow capsules, vegetable capsules have the advantages of wide adaptability, no risk of cross-linking reaction, and high stability. The drug release rate is relatively stable, and individual differences are small. After disintegration in the human body, it is not absorbed and can be excreted. Excreted from the body. In terms of storage conditions, after a lot of tests, it is almost not brittle under low humidity conditions, and the properties of the capsule shell are still stable under high humidity, and the various indexes of plant capsules under extreme storage conditions are not affected. With people’s understanding of plant capsules and the transformation of public medicine concepts at home and abroad, the market demand for plant capsules will grow rapidly.
The fifth is as a suspending agent. Suspension type liquid preparation is a commonly used clinical dosage form, which is a heterogeneous dispersion system in which hardly soluble solid drugs are dispersed in a liquid dispersion medium. The stability of the system determines the quality of suspension liquid preparations. HPMC colloidal solution can reduce the solid-liquid interfacial tension, reduce the surface free energy of solid particles, and stabilize the heterogeneous dispersion system. It is an excellent suspending agent. HPMC is used as a thickener for eye drops, with a content of 0.45% to 1.0%.
Hydroxypropyl cellulose (HPC) is a non-ionic cellulose monoether made from cotton and wood through alkalization and propylene oxide etherification. HPC is usually soluble in water below 40°C and a large amount of polar solvents, and its performance is related to the content of hydroxypropyl and the degree of polymerization. HPC can be compatible with various drugs and has good inertness.
Low-substituted hydroxypropyl cellulose (L-HPC) is mainly used as a tablet disintegrant and binder. Its characteristics are: easy to press and form, strong applicability, especially difficult to form, plastic and brittle tablets, add L －HPC can improve the hardness of the tablet and the brightness of the appearance, and it can also make the tablet disintegrate quickly, improve the internal quality of the tablet, and improve the curative effect.
High substituted hydroxypropyl cellulose (H-HPC) can be used as a binding agent for tablets, granules and fine granules in the pharmaceutical field. H-HPC has excellent film-forming properties, and the resulting film is tough and elastic, which can be compared with plasticizers. By mixing with other anti-wet coating agents, the performance of the film can be further improved, and it is often used as a film coating material for tablets. H-HPC can also be used as a matrix material to prepare matrix sustained-release tablets, sustained-release pellets and double-layer sustained-release tablets.
Hydroxyethyl cellulose (HEC) is a non-ionic cellulose monoether made from cotton and wood through alkalization and ethylene oxide etherification. HEC is mainly used as a thickener, colloidal protective agent, adhesive, dispersant, stabilizer, suspending agent, film-forming agent and slow-release material in the medical field. It can be applied to emulsions, ointments, and eye drops for topical medication. Oral liquid, solid tablets, capsules and other dosage forms. Hydroxyethyl cellulose has been included in the U.S. Pharmacopoeia/U.S. National Formulary and European Pharmacopoeia.
Ethyl cellulose (EC) is one of the most widely used water-insoluble cellulose derivatives. EC is non-toxic, stable, insoluble in water, acid or alkaline solutions, and soluble in organic solvents such as ethanol and methanol. The commonly used solvent is a mixed solvent of toluene/ethanol 4/1 (weight). EC has many uses in drug sustained-release preparations, and is widely used as a carrier and microcapsules, coating film-forming materials, etc. of sustained-release preparations, such as tablet retarders, adhesives, film coating materials, etc. It is used as a matrix material film to prepare various types of matrix sustained-release tablets, as a mixed material to prepare coated sustained-release preparations and sustained-release pellets, as a encapsulation auxiliary material to prepare sustained-release microcapsules; it can also be widely used as a carrier material It is used to prepare solid dispersions; it can be widely used in pharmaceutical technology as a film-forming substance and protective coating, and it can also be used as a binder and filler. As a protective coating for tablets, it can reduce the sensitivity of the tablets to humidity and prevent the drugs from becoming discolored and deteriorated by moisture; it can also form a slow-release glue layer and microencapsulate the polymer to continuously release the drug effect.
In summary, the water-soluble sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose and oil-soluble ethyl cellulose are all based on their respective The characteristics of the product are used in pharmaceutical excipients as adhesives, disintegrants, sustained and controlled release materials for oral preparations, coating film-forming agents, capsule materials and suspending agents. Looking at the world, several foreign multinational companies (Shin-Etsu Japan, Dow Wolff and Ashland ) realized the huge market for pharmaceutical cellulose in China in the future, and either increased production or mergers, they have increased their presence in this field. Investment within the application. Dow Wolff announced that it will increase its attention to the formulation, ingredients and needs of the Chinese pharmaceutical preparation market, and its application research will also strive to get closer to the market. The Wolff Cellulose Division of Dow Chemical and Colorcon Corporation of the United States have established a sustained and controlled release preparation alliance globally. It has more than 1,200 employees in 9 cities, 15 asset institutions and 6 GMP companies. Applied research professionals provide services to clients in approximately 160 countries. Ashland has production bases in Beijing, Tianjin, Shanghai, Nanjing, Changzhou, Kunshan and Jiangmen, and has invested in three technology research centers in Shanghai and Nanjing.
According to statistics from the website of the China Cellulose Association, in 2017, the domestic production of cellulose ether was 373,000 tons and the sales volume was 360 thousand tons. In 2017, the actual sales volume of ionic CMC was 234,000 tons, an increase of 18.61% year-on-year, and the sales volume of non-ionic CMC was 126,000 tons, an increase of 8.2% year-on-year. In addition to HPMC (building material grade) non-ionic products, HPMC (pharmaceutical grade), HPMC (food grade), HEC, HPC, MC, HEMC, etc. have all risen against the trend, and production and sales have continued to increase. Domestic cellulose ethers have been growing rapidly for more than ten years, and the output has become the world’s first. However, most of the cellulose ether companies’ products are mainly used in the middle and low end of the industry, and the added value is not high.
At present, most of the domestic cellulose ether enterprises are in a critical period of transformation and upgrading. They should continue to increase product research and development efforts, continuously enrich product varieties, make full use of China, the world’s largest market, and increase efforts to develop foreign markets so that enterprises will be able to expand as soon as possible. Complete the transformation and upgrade, enter the mid-to-high end of the industry, and achieve benign and green development.
Post time: Apr-25-2024