Pharmaceutical excipients are excipients and adjuncts used in the production and dispensing of drugs, and are an important part of pharmaceutical preparations. Cellulose ether as derived from natural polymer material, has the characteristics of biodegradable, nontoxic, cheap, such as sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, ethyl cellulose and hydroxyethyl cellulose, cellulose ether has important application value in the pharmaceutical excipients. At present, most of the products of domestic cellulose ether enterprises are mainly applied to the low-end of the industry, the added value is not high, the industry is in urgent need of transformation and upgrading, improve the high-end application of products.

Pharmaceutical excipients market potential is huge

Pharmaceutical excipients play an important role in the development and production of pharmaceutical preparation. For example, in sustained-release preparations, cellulose ether and other polymer materials as pharmaceutical excipients have been widely used in sustained-release pellets, various framework sustained-release preparations, coating sustained-release preparations, sustained-release capsules, sustained-release film, resin drug sustained-release preparations and liquid sustained-release preparations. In this system, cellulose ether and other polymers are generally used as the carrier of drugs to control the release rate of drugs in the human body, that is, they are required to be released slowly in the body at a set rate within a certain time range to achieve the purpose of effective treatment.

According to the statistics of zhiyan Consulting and research Department, China has been listed about 500 kinds of excipients, but compared with the United States (more than 1500 kinds), the European Union (more than 3000 kinds), there is a great gap, the type is still less, China’s pharmaceutical excipients market development potential is huge. It is understood that the top ten pharmaceutical excipients in China market are pharmaceutical gelatin capsule, sucrose, starch, film coating powder, 1, 2-propylene glycol, PVP, hydroxypropyl methyl cellulose (HPMC), microcrystalline cellulose, HPC, lactose.

Six kinds of cellulose ether?in pharmaceutical excipients

Natural cellulose ether is alkali cellulose and etherifying agent under certain conditions of reaction to generate a series of cellulose derivatives, is a cellulose macromolecule hydroxyl ether group is partially or completely replaced by the product. Cellulose ether is widely used in petroleum, building materials, coatings, food, medicine and daily chemicals and other fields, in all fields, pharmaceutical products are basically in the high-end field of the industry, with high added value. Due to strict quality requirements, the production of pharmaceutical grade cellulose ether is also more difficult, it can be said that the quality of pharmaceutical grade products can represent the technical strength of cellulose ether enterprises. Cellulose ether is usually used as a blocker, skeleton material and viscosifier to add, made of sustained-release skeleton tablet, stomach soluble coating material, sustained-release microcapsule packaging material, sustained-release drug film agent materials.

Sodium carboxymethyl cellulose

Sodium carboxymethyl cellulose (CMC-NA) is the largest yield and dosage of cellulose ether varieties at home and abroad, is made of cotton, wood by alkali, chloroacetic acid etherification and other processes made of ionic cellulose ether. Cmc-na is a kind of commonly used pharmaceutical excipients, commonly used as adhesives for solid preparations and viscous, thickening and suspension AIDS for liquid preparations, as well as water-soluble matrix and film forming materials. In slow (controlled) release preparations, it is often used as film agent material for slow release drugs and framework tablets for slow release.

In addition to sodium carboxymethyl cellulose as pharmaceutical excipients, crosslinked sodium carboxymethyl cellulose can also be used as pharmaceutical excipients. Crosslinked sodium carboxymethyl cellulose (CCMC-NA) is a purified water insoluble substance of carboxymethyl cellulose reacted with crosslinking agent at a certain temperature (40 ~ 80℃) under the action of inorganic acid catalyst. The crosslinking agent can be propylene glycol, succinic anhydride, maleic anhydride and adipic anhydride. Crosslinked sodium carboxymethyl cellulose is used as a disintegrating agent of tablets, capsules and granules in oral preparations, relying on capillary and swelling to have the effect of disintegrating, its good compressibility, strong disintegrating force. Studies have shown that the swelling degree of crosslinked sodium carboxymethyl cellulose in water is greater than that of low-substituted sodium carboxymethyl cellulose and hydrated microcrystalline cellulose and other common disintegrating agents.

Methyl cellulose

Methyl cellulose (MC) is a single nonionic cellulose ether made from cotton and wood by alkalization, chloromethane etherification and other processes. Methyl cellulose has excellent water solubility and is stable in the pH range of 2.0~13.0. It is widely used in pharmaceutical excipients, sublingual tablets, intramuscular injections, ophthalmic preparations, oral capsules, oral suspensions, oral tablets and local preparations. In addition, MC can be used as hydrophilic gel framework sustained-release preparation, gastric soluble coating material, sustained-release microcapsule coating material, sustained-release drug film agent material, etc.

Hydroxypropyl methyl cellulose

Hydroxypropyl methyl cellulose (HPMC) is a nonionic cellulose mixed ether made from cotton and wood by alkalization, propylene oxide and chloromethane etherification. It is odorless, tasteless and non-toxic, soluble in cold water and gelatinous in hot water. Hydroxypropyl methyl cellulose is the domestic yield, dosage and quality of cellulose mixed ether varieties in the past 15 years are rapidly improving, is also one of the largest amount of medicinal excipients at home and abroad, as a medicinal excipient has nearly 50 years of history. At present, HPMC application is mainly reflected in the following five aspects:

One is as a binder and disintegrating agent. HPMC as a binder can make the drug easy to wet, and its own water can expand hundreds of times, so it can significantly improve the dissolution or release of tablets. HPMC has strong viscosity, for the texture of crisp or brittle hard raw materials can enhance its particle viscosity, improve its compressibility. HPMC low viscosity can be used as a binder and disintegrating agent, high viscosity only as a binder.

The second is as a slow and controlled release material for oral preparations. HPMC is a hydrogel framework material commonly used in sustained-release preparations. HPMC with low viscosity level (5 ~ 50mPa·s) can be used as adhesive, adhesive-enhancing agent and suspension aid, while HPMC with high viscosity level (4000 ~ 100000mPa·s) can be used as a blocker for the preparation of mixed materials framework sustained-release tablets, sustained-release capsules and hydrophilic gel framework sustained-release tablets. HPMC can be dissolved in gastric enteric fluid, has the advantages of good pressability, good fluidity, strong drug loading ability and drug release characteristics are not affected by pH, etc., is a very important hydrophilic carrier material in sustained release preparation system, commonly used as hydrophilic gel framework and coating material of sustained release preparation, and used in gastric floating preparation, sustained release drug film agent excipients.

Third, as a coating film – forming agent. HPMC has good film forming, it forms the film uniform, transparent, tough, production is not easy to stick, especially for easy moisture absorption, unstable drugs, with it as isolation layer can greatly improve the stability of drugs, prevent film discoloration. HPMC has a variety of viscosity specifications, such as proper selection, coating film quality, appearance is better than other materials, its commonly used concentration of 2% ~ 10%.

The fourth is as capsule capsule material. In recent years, with the frequent outbreak of animal epidemic worldwide, compared with gelatin capsules, plant capsules have become the new darling of the pharmaceutical and food industry. Pfizer has successfully extracted HPMC from natural plants and prepared VcapTM plant capsules. Compared with the traditional gelatin hollow capsules, plant capsules have the advantages of wide adaptability, no cross-linking reaction risk and high stability. The drug release rate is relatively stable, the individual differences are small, and they are not absorbed after disintegrating in the human body, and can be discharged from the body with feces. In terms of storage conditions, through a large number of experiments, the capsules are almost not brittle under low humidity conditions, and the properties of capsules are still stable under high humidity conditions, and the indexes of plant capsules are not affected under extreme storage conditions. With people’s understanding of plant capsules, as well as the change of public drug concept at home and abroad, the market demand of plant capsules will grow rapidly.

Five is as a suspension agent. Suspended liquid preparations are commonly used in clinical dosage forms, which are heterogeneous dispersion systems of insoluble solid drugs in liquid dispersion media. The stability of the system determines the quality of suspended liquid preparation. HPMC colloidal solution can reduce the solid-liquid interface tension, reduce the surface free energy of solid particles, so that the heterogeneous dispersion system tends to be stable, is an excellent suspension agent. HPMC is used as the thickener of eye drops, and the content is 0.45% ~ 1.0%.

Hydroxypropyl cellulose

Hydroxypropyl cellulose (HPC) is a single nonionic cellulose ether made from cotton and wood by alkalization, propylene oxide etherification and other processes. HPC is usually soluble in water below 40℃ and a large number of polar solvents. Its properties are related to the content of hydroxypropyl and degree of polymerization. HPC can be compatible with various drugs and has good inertia.

Low substituted hydroxypropyl cellulose (L – HPC) mainly for tablet disintegrants and adhesive, its features are: easy to suppress forming, strong applicability, especially not easy molding, plasticity and brittleness of film, joined the L – HPC can increase the hardness of tablet and the appearance of brightness, still can make tablet disintegrated rapidly, promote the intrinsic quality of the film, and improve the curative effect.

High substituted hydroxypropyl cellulose (H-HPC) can be used as a binder for tablet, granule and fine granule in the pharmaceutical field. H-HPC has excellent film forming property, the film obtained is tough and elastic, and can be compared with plasticizer. By mixing with other anti-moisture coating agents, the film performance can be further improved, and is commonly used as a film coating material for tablets. H-hpc can also be used as framework material to prepare framework sustained-release tablets, sustained-release pellets and double-layer sustained-release tablets.

Hydroxyethyl cellulose

Hydroxyethyl cellulose (HEC) is a single nonionic cellulose ether made from cotton and wood by alkalization, ethylene oxide etherification and other processes. HEC is mainly used as thickener, colloidal protective agent, adhesive, dispersant, stabilizer, suspension agent, film forming agent and sustained-release material in the medical field. It can be used in local drug emulsions, ointments, eye drops, oral liquid, solid tablets, capsules and other dosage forms. Hydroxyethyl cellulose has been included in the United States Pharmacopoeia/United States National Formulary and European pharmacopoeia.

Ethyl cellulose

Ethyl cellulose (EC) is one of the most widely used water-insoluble cellulose derivatives. EC is non-toxic and stable, insoluble in water, acid or alkali solutions, soluble in ethanol, methanol and other organic solvents. Common solvents are toluene/ethanol mixtures of 4/1 by weight. EC has many USES in drug controlled-release formulation, widely used as a carrier of the controlled-release formulation and micro capsule, coating film materials, such as: can be used as a tablet blockers, adhesive, film coating material, used as skeleton materials membrane preparation of various types of skeleton zyban, used as a mixed material prepare coating sustained-release preparations, slow release micro pill, used as packing materials preparation of slow release micro capsule; It can also be widely used as a carrier material to prepare solid dispersion. It is widely used in pharmaceutical technology as a film forming substance and protective coating, as well as as a binder and filler. As the protective coating of tablets, it can reduce the sensitivity of tablets to humidity and prevent the drugs from being affected by damp and discoloration. It can also form a slow-release adhesive layer and encapsulate the polymer with microcapsules, so that the drug effect can be released continuously.

We will get rid of mid – and low-end applications and accelerate transformation and upgrading

To sum up, the water-soluble sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose and oil soluble ethyl cellulose with their respective features, as a binder, disintegrating agent, oral preparations slow controlled release materials, coating film formers, capsule capsule material and suspended aid used in the pharmaceutical excipients. Looking at the world, several foreign multinational companies (Japan Shin-Etsu, the United States Dow Wolf and Ashland ) realize the huge market of pharmaceutical cellulose in China in the future, or increase production, or merger, have increased the application investment in this field. Dow Announced that it will step up its focus on the formulations, ingredients and needs of the Chinese pharmaceutical market, as well as its efforts to bring applied research closer to the market. Dow’s Cellulose division and colorcon have established a global alliance for controlled-release formulations, with more than 1,200 employees in 9 cities, 15 asset facilities and 6 GMP companies, and a large number of applied research professionals serving customers in approximately 160 countries. Ashland has manufacturing facilities in Beijing, Tianjin, Shanghai, Nanjing, Changzhou, Kunshan and Jiangmen, and has invested in three technology research centers in Shanghai and Nanjing.

According to the website of the China Cellulose?ether?Association, in 2017, the domestic output of cellulose ether was 373,000 tons, and the sales volume was 360,000 tons. In 2017, the actual sales volume of ionic CMC was 234,000 tons, up 18.61% year on year, and that of non-ionic CMC was 126,000 tons, up 8.2% year on year. Non-ionic products in addition to HPMC(building materials), HPMC(pharmaceutical), HPMC(food), HEC, HPC, MC, HEMC and so on are bucking the trend and increasing production and sales. Domestic cellulose ether has grown rapidly for more than ten years, output has become the world’s first, but most of the products of cellulose ether enterprises are mainly applied to the low-end of the industry, the added value is not high.

Various cellulose ether enterprise at home and abroad, mostly in the critical period of transformation and upgrading, should continue to strengthen product development, enrich the varieties of products, make full use of the world’s largest market, and intensify efforts to develop the foreign market, make the enterprise to complete the transformation and upgrading as soon as possible, into the high-end in the field of industry, realize the benign and green development.