Crushing and granulating technology to solve the problem of Chinese medicine capsule preparation
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The problem of the production process of traditional Chinese medicine capsules is to be solved. The common Chinese medicine capsules generally have the common problem of taking a large amount of tablets, causing the number of grains to be filled, the moisture content of the filling contents to be easy to absorb moisture, and the roundness of the particles are not good. The easy moisture absorption and bonding is a key issue to be solved.
Taking more capsules, traditional Chinese medicine capsules generally take too many capsules, especially some compounds containing more tonic herbs, such as: Bailing Capsule, 5 to 15 capsules a day, 3 times a day; Weitaiping capsule, 8 capsules at a time 3 times a day; Guifu Dihuang capsule, 7 capsules at a time, 2 times a day. The excessive number of capsules taken by the capsule is mainly related to the high solid matter yield after the raw material extraction, the amount of the auxiliary materials, and the shortage of various granulation methods of the traditional Chinese medicine.
For the solid matter yield is too high, the static precipitation method, the water extraction and alcohol precipitation method, the clarification agent filtration method, the high-speed centrifugal filtration method and the like are often used to reduce the impurities in the raw material extraction to reduce the amount of the leachate. . However, due to the material basis research of traditional Chinese medicine preparations, especially the material basis research of compound preparations, it is difficult to make breakthroughs. Therefore, it is difficult to reduce the number of capsules taken by the artisan.
Excipient application plays an extremely important role in the development and use of modern preparations. At present, the extract of traditional Chinese medicine is still a crude extract, and the volume is larger, and the use of the auxiliary material makes the taking volume larger, and the capsule takes more particles. Moreover, existing granulation techniques have more or less problems, and the prepared granules cannot achieve the purpose of reducing the number of capsules or reducing the size of the capsule.
Moisture-absorbing bonding Due to the complex and diverse content and form of the contents of the filled capsules, most of the capsules often have the phenomenon of moisture absorption, adhesion and even mildew in the storage process, which has become one of the important reasons affecting the quality and efficacy of the drug. Nowadays, it is generally used to improve the situation by using packaging materials. The common method is to add a moisture-proof aluminum-plastic bag to the aluminum-plastic panel to achieve moisture-proof purposes.
The contents of traditional Chinese medicine capsules are generally granules. However, due to the problems of the existing granulation technology, the particle size is not uniform and the appearance is not round. It is precisely because of the small density of the particles themselves and the large specific surface area that the hygroscopicity cannot be effectively improved, which is one of the reasons why the content of the capsule is easy to absorb moisture, and at the same time, the particle coating technology is difficult to realize, and Easy to pack.
Chinese scholars have proposed that the traditional Chinese medicine preparation process of the squeezing granulation technology is divided into two parts: the extraction process and the molding process. The selection from the relatively small molding process, starting from the granulation point of view, may be able to effectively solve the above problems of traditional Chinese medicine capsules. Some scholars in our country have envisaged the concept of "compressed granules" (such as compressed biscuits) to solve the common problems in the production of Chinese medicine capsules.
Assume that the total volume of the capsule is V, and the daily dosage of the preparation is M. According to the formula M=ÏV, since M is constant, to reduce V, it is necessary to increase the bulk density Ï of the particles, that is, to reduce the number of tablets to be taken, it is necessary to increase significantly. Particle bulk density. If the prepared particles have a reduced specific surface area, the appearance is smooth and round, and the texture is compact, not only has strong anti-wetting property, but also facilitates coating. Through film coating, not only can the particle's anti-wetting property be more effectively enhanced, but also a special drug delivery system can be made by wrapping a special material, and at the same time, the appearance color of the particles can be changed, and the patient compliance can be improved.
At present, various granulation techniques, including wet granulation, dry granulation, spray granulation, fluidized bed granulation, etc., are not rough surface, large specific surface area, loose texture, low bulk density, and no method. It can meet the requirements of reducing the number of capsules and solving or improving the moisture-proof bonding of particles.
In order to meet the requirements of the pellets, on the basis of the extrusion granulation technology, Chinese researchers have improved a granulation principle to obtain a new granulation technology--the extrusion granulation technology, that is, the twin-screw The strong pressure granulator is the main process equipment. After the material is wetted and mixed, it is made into a soft material, and then made into a sphere or a class by hard extrusion, rotary pelletizing, friction rolling, drying and expansion into balls. Spherical particles, the resulting particles are named "squeezed particles" or "compressed particles."
The squeeze granulation technology can increase the particle bulk density, increase the capsule dosage while changing the single dose; and use less or no auxiliary materials when preparing the capsule, thereby reducing the capsule dosage or reducing the capsule size. Improve patient compliance. In addition, this technology can effectively reduce the specific surface area of ​​the particles and increase the tightness of the particles, thereby preventing the adsorption of more moisture and achieving the purpose of moisture prevention. At the same time, due to the rounded appearance of the prepared particles, the true sphericity is high and the strength is large, which facilitates the particle coating, and the coating can more effectively prevent moisture.
The application prospect of squeeze granulation technology is worth looking forward to the extrusion granule technology brings new ideas for the research and development of new Chinese medicines and new preparations, which can be promoted and applied in the following fields.
First, it is applied to the secondary development of traditional Chinese medicine preparations. Some modified type varieties, due to more extracts, lead to a large single dose, the choice of dosage form can not choose capsules, tablets and other small drug-loaded dosage forms, but only granules, pills and other dosage forms, although The drug is large, but it lacks market competitiveness. Some imitations with a large number of grains are used to increase the thinness of the drug's taste layer or to increase the sample content limit to improve the quality of the variety. After imitation, the patient's compliance is still poor.
If the squeezing granulation is used for the secondary development of the traditional Chinese medicine preparation, by reducing the number of tablets taken or reducing the size of the capsule shell, it is possible to consider not only the dosage form of capsules, tablets and the like, but also the preparation of the dosage form, and the preparation of the preparation. The species can significantly improve patient compliance and enhance market competitiveness.
The second is applied to new drug delivery systems. Taking the pulse release system in the release mechanism of sustained-release pellets as an example, the pulse-release pellets, also known as the time-controlled burst system (TES), are released in a specific part of the gastrointestinal tract (such as the stomach and colon) by timing control. The release method is in line with the change of the human circadian rhythm.
The pellets are divided into four layers from the inside to the outside: a pellet core-drug layer-intumescent layer-water insoluble polymer outer coating film. Usually, the sugar pellet is used as a pellet core, and the hydrophilic and hydrophobic drugs are respectively used as a drug layer, and then the swelling layer is wrapped, and after the Zui, the TES is made by using ethyl cellulose as the outer coating film.
The study found that the size of TES depends on the size of the core, the thickness of the drug layer and the swelling layer, and the release rate depends on the solubility of the drug, and does not depend on the external pH (because the membrane is not affected by pH), so the pellet The preparation of the core determines whether the pellets are good or bad. The pellet core is required to have a uniform size, a round shape, a good sphericity, and a certain strength, and the compressed granule can satisfy these requirements, so the pellet core used for preparing the sustained-release pellet can be considered.
In addition, the extrusion granulation technique can be applied not only to the preparation of capsules but also to granules, pellets and the like. It has been found that when the content of the material above 80% is made into squeezed particles, under certain temperature conditions, when the particles contain a wetting agent (generally water and ethanol) above 10%, the extruded particles are all puffed into spherical particles. Its appearance is exactly the same as that of pellets. Granules, formulated granules, instant pellets and the like can be prepared by using such particles. The prepared pellets are hollow and puffed, and have good meltability and dissolvability.
The promotion and application of squeeze granulation technology still needs to solve some basic problems. As we all know, just like the smashing of traditional Chinese medicine, different degrees of comminution can show different properties. The powder passing through the 100 mesh sieve is called fine powder, the sieve that is over 120 mesh is called zui fine powder, and the 200 mesh is called ultrafine powder. How do you express 300 mesh and 400 mesh? Since the powder reaches a certain fineness, it exhibits different physical and chemical properties from the ordinary powder, and thus has the concept of powder theory. Is there a similar situation in the extrusion granule technology? Compared with the general extrusion granulation technology, the same is done by mechanical force extrusion granulation, the difference is only the pressure level, but the physicochemical properties of the particles which are different from other particles, whether the pre-extrusion particles may be different from any previous ones Is the granule a new granule? These questions have yet to be answered in in-depth experimental research.
Related links squeeze granulation naming basis*, in engineering, the granulation technology that presses the material into a certain shape by external force is collectively called compression granulation technology, such as dry pressed granules, which can also be called compression in engineering. Granulation, while extrusion granulation mentioned in pharmacy, is also a form of compression granulation; second, according to technical characteristics, using strong propulsion is called "pressure", compared with other particles, the unit The reduction of the specific surface area of ​​the mass particles is called "shrinking". This technology is an improvement in the original extrusion technology. For the sake of distinction, the technology is temporarily named "squeezing granulation technology".
During the application of the squeezing granulation technology, it was found that the granules produced under certain temperature conditions were prone to swell and sometimes even burst; the color of the granules generally deepened and the time limit of disintegration of some whole medicinal powder granules was unqualified. These phenomena are different from those produced by other granulation methods, and it is suggested that the physical properties of the particles may change after strong extrusion. Therefore, the pellets produced by the squeeze granulation technique are referred to as "squeezing granules" or "compressed granules".
Basic principle and technical characteristics of squeeze granulation The squeezing granulation adopts the twin-screw strong pressure granulator as the process equipment. After the soft material made of the wetting agent mixture passes through the machine, it is subjected to hard extrusion, rotary dicing and drying. It is made into a spherical or spheroidal particle with a rounded appearance and a smooth surface.
The main features of the squeeze granulation technology are summarized as follows. First, the density of the prepared particles is larger than that of ordinary particles. When the particles are filled with the particles, the filling amount will be significantly increased. Taking the No. 0 capsule as an example, the large filling amount of zui can reach 0.65 g (generally, the other particles have a large filling amount of 0.50 g). This technique not only increases the drug loading of the capsule, but also reduces the number of tablets taken without changing the original dosage. Second, the particle has a small specific surface area, a smooth and round appearance, and a compact texture. Third, it can effectively reduce the amount of preparations used in the preparation. For the extraction preparation, the ratio of the auxiliary materials is 3% to 8%, and the alcohol extract is 8% to 15%. The traditional Chinese medicine powder generally does not need excipients.