■New technologies and new excipients are constantly being introduced
Most solid preparations must go through the granulation process. In recent years, with the development of the pharmaceutical industry, granulation technology has also been greatly improved, which has greatly promoted the traditional Chinese medicine preparation technology.
Fluidized bed granulation technology (one-step granulation technology) is a more popular granulation technology. Its characteristics are: greatly reducing the amount of excipients, and the content of extract in the granules can reach 50-70% ; The particles are formed in the boiling state, with round surfaces and good fluidity. At the same time, since the granulation process is completed in a closed granulator, the production process is not easily contaminated, and the quality of the finished product can be well guaranteed. Shanghai No. 2 Traditional Chinese Medicine Factory once used fluidized spray drying technology to improve the Yinqiao tablet process. It not only reduced the granulation process, but also produced loose and porous granules. After tableting, it has high hardness and rapid disintegration, which improves tablet quality. .
Rapid mixing granulation technology is a granulation technology completed by using a rapid mixing granulator. Usually, the container containing solid materials (auxiliary materials) is lifted and sealed, and the traditional Chinese medicine extract is added through the feeding port, and three openings are opened. The stirring blade rotates at a certain speed, causing the material to be thrown up in a rotating wave from the bottom of the container along the wall. The wave crest is cut into small pieces with certain edges and corners by the high-speed rotating scraper, and the small pieces rub against each other. Finally, spherical particles are formed. The granules produced by this method are uniform and round, the amount of auxiliary materials is small, and the granulation process is airtight and fast.
Traditional Chinese medicine granules, tablets, and pills have the disadvantages of being highly hygroscopic, easy to splinter, and become moldy. The application of film coating technology can overcome these shortcomings. Traditional film coating materials mainly include gastric-soluble and enteric (small intestine)-soluble types. With the synthesis of new pH-sensitive coating materials, localized drug delivery in the large intestine and colon becomes possible. By selecting coating materials and designing the coating formula, the coating film can be dissolved or disintegrated within a certain pH value range, and the permeability of the film can also be controlled, so that the coated drugs can be gradually released in the body to achieve a constant The purpose of release, sustained release, immediate release, or the drug is made into a positioning tablet that is released at the point of action and a targeted preparation that delivers the drug accurately into the target tissue. Domestic pharmaceutical manufacturers have made full use of this technology, not only using it in ordinary tablets, but also in various dosage forms such as water pills.
At present, β-cyclodextrin (β-Cyclodextrin) inclusion compounds have been widely used in the field of traditional Chinese medicine preparations. It can increase the solubility of drugs, improve the stability of drugs, powderize liquid drugs, and prevent Volatile ingredients evaporate, reducing the irritation and toxicity of the drug. Researchers from Yunnan College of Traditional Chinese Medicine once used β-cyclodextrin to contain the volatile oils of peppermint and Schizonepeta in Yinqiao Jiedu Granules, and selected the inclusion process conditions based on the utilization rate of volatile oils as the main indicator. The study was carried out under the conditions that the ratio of oil to β-cyclodextrin was 1:8 (ml:g), the inclusion temperature was 30°C, and the inclusion time was 1 hour, and TLC (thin layer chromatography) was used to check the inclusion. Stability of volatile oils before and after. The final results show that the β-cyclodextrin inclusion process can more effectively preserve the active components of volatile oil and improve its stability.
Solid dispersion technology refers to a technical system in which drugs are uniformly dispersed in a solid carrier in the form of particles, microcrystals or molecules. Using highly water-soluble or hydrophilic substances as solid dispersion carriers can increase the solubility and dissolution rate of poorly soluble drugs, and increase the bioavailability of drugs. Currently, products using this technology include Compound Danshen Dropping Pills and Su Bing Drops. Pills, Xianglian dripping pills, etc. In recent years, this technology has also been well used in sustained-release preparations. Research has proven that the use of water-insoluble carriers or poorly soluble materials as carriers can prevent drug release and achieve sustained or controlled release, such as the sustained release of artemether solid dispersions made with enteric material acrylic resin No. Ⅱ as the carrier. preparation.
Micro-encapsulation technology is a technology that uses polymer materials to embed powder particles or liquid droplets into tiny capsules. After the drug is microencapsulated, the stability is improved, the efficacy is prolonged, and the bad odor is masked. Researchers have studied natural pharmaceutical ingredients such as tetrandrine, cantharidin, paclitaxel, artemisinin, and harringtonine, and the results have been good. But there are still many problems with microcapsules.
Research on the control of average particle size, control of drug release rate at the target site, and biodegradable and absorbable capsule materials needs to be further strengthened.
■Research on new dosage forms of traditional Chinese medicine has made gratifying progress
With the research progress of new formulation technologies and the improvement of preparation processes, many new dosage forms of traditional Chinese medicine have appeared in China.
TCM tablets are one of the fastest growing new dosage forms of traditional Chinese medicine, with more than 1,000 varieties currently available. Relevant types include compressed tablets, sugar-coated tablets, buccal tablets, effervescent tablets, solution tablets, microencapsulated tablets, gastric floating tablets, sustained-release tablets, etc. If traditional Chinese medicine tablets contain less viscous ingredients, more loose ingredients, or drugs with strong oiliness, they will easily cause splitting; extract tablets contain a large amount of moisture-absorbing ingredients, which are prone to moisture, softening, sticking, and mildew. Generally, removing moisture-absorbing ingredients is used to remove the moisture-absorbing ingredients. Impurities can be solved by adding moisture-proof auxiliary materials or coating.
In recent years, scientific and technical personnel have applied new preparation technologies to develop some varieties with clear action characteristics and good curative effects, such as compound guaiacol glyceryl ether double-layer sustained-release tablets, Weiyoujing floating tablets, Wuhuang hemostatic effervescent tablets.
Capsules include hard capsules and soft capsules. Soft capsules can mask the unpleasant smell and taste of drugs, are convenient to take, and are easy to accept. They have become a hot spot in R&D and production. Drugs that are sensitive to light, unstable when exposed to moisture and heat, and easily oxidized, oily drugs, and drugs with low melting points are suitable for soft capsules. At the same time, soft capsules omit adsorption excipients, miniaturize the preparation, and avoid drug dissociation and leakage. At present, many traditional Chinese medicines have been made into soft capsules, such as Huoxiang Zhengqi soft capsules, Xinganmao soft capsules, and Vitex oil capsules sold on the market.
Granules have the characteristics of traditional decoctions or powders, and overcome many of their shortcomings. They have high bioavailability, simple production processes, and are easy to implement mechanized production. Due to the application of new technologies and new excipients such as ultrafiltration technology, flocculation and clarification technology, and fluidized granulation technology, granules have developed rapidly. On the basis of the original varieties, sugar-free granules and effervescent granules have been developed. Such as sugar-free Huazhen granules, Shaogan analgesic effervescent granules, etc.
There are two main types of traditional Chinese medicine dripping pills: one is prepared by dispersing oily ingredients in the matrix and using the dripping method; the other is traditional Chinese medicine that is insoluble in water, has a slow dissolution rate and is poorly absorbed. The ingredients or effective parts are prepared using solid dispersion technology to prepare quick-acting dropping pills. The drug loading capacity of dripping pills is small, and the raw materials must be refined to enrich the active ingredients or effective parts. Such products currently on the market include Tripterygium wilfordii dropping pills, Pueraria lobata flavonoid dropping pills, etc.
*Parental administration dosage form
The film coating agent has a simple preparation process and is easy to use, and has a good effect in the prevention and treatment of some skin diseases, occupational diseases, etc. At present, several coating agents are only produced in hospital preparation rooms and used internally in hospitals, and the quality control of preparations is only in the preliminary exploratory stage. Compound Chinese medicine has complex components, and some components may react physically or chemically with the film-forming materials, destroying the stability of the coating agent. In addition, the drug loading capacity of the film coating agent is also small. Therefore, further research is needed on the development of film coating agents.
At present, there are many research and development and applications of styling cataplasms. It uses water-soluble polymer as the base of the drug. It does not stick to the skin and has no skin allergic reaction like rubber plaster. It has good moisturizing properties and can easily soften the cuticle of the skin, thereby facilitating the absorption of the drug. At present, domestic cataplasm products include antiasthmatic and cough patches, qi and laxative patches made of Miao medicinal ingredients such as Jixiangcao and Aidi tea, as well as Schisandra chinensis cataplasm and Wu Xing Sanba made of PVA as the base. Cloth agent, Xingqianba cloth agent, etc. However, there is still a lack of in-depth research on the matrix and preparation process of cataplasm. As the ingredients of traditional Chinese medicine aqueous extract are complex, the application of cataplasm in traditional Chinese medicine preparations still has certain limitations.
Aerosols and sprays can directly reach the site of action through the respiratory tract, are effective and easy to use. Some traditional Chinese compound medicines used for first aid in China have been developed into aerosols. For example, the Heart-saving Aerosol developed by researchers at the Jilin Institute of Traditional Chinese Medicine is used to treat angina pectoris attacks. However, the small drug loading capacity of aerosols and the limitations of propellants make many traditional Chinese medicines unsuitable for making aerosols.
TCM injections have been widely used in clinical practice to meet the needs of TCM emergency medication.
Some active monomers isolated from Chinese herbal medicines have made gratifying progress using new technologies. Related products include astragalus polysaccharide liposome injection, paclitaxel liposome lyophilized injection, harringtonine nanocapsule injection, camptothecin solid lipid nanoparticle injection, ligustrazine hydrochloride lung-targeted microsphere injection, etc. Researchers at China Pharmaceutical University once combined the traditional Chinese medicine compound "Sanjie Huayu Granule Extract" with 5-Fu to create a magnetic microsphere preparation for the treatment of tumors. However, some industry experts pointed out that due to the complex ingredients of traditional Chinese medicine, traditional Chinese medicine injections have shortcomings such as poor stability, high irritation, and prone to precipitation.