Solid drug preparations account for about 70% to 80% of pharmaceutical products. The dosage forms containing solid drugs include powders, granules, capsules, tablets, powder injections, and suspensions. For example, we use ibuprofen sustained-release capsules, ibuprofen suspensions, cold granules, etc. in curing COVID-19. These are actually closely related to powder materials. The production processes involved include crushing, grading, mixing, granulation, etc. Some solid drug preparations need to be modified during the preparation process to improve the properties of the powder to meet the needs of product quality and powder operation. In addition to the above-mentioned solid drug preparations themselves requiring crushing, some raw materials also need to rely on the catalytic reduction of metal powders during preparation.
The application of metal powders in medicine also involves different morphology controls. Among them, spherical powders are mostly prepared by liquid and gas phase methods, and flaky powders are mostly prepared by solid phase methods. The particle size, purity and mass fraction of trace elements of metal powders play a decisive role in the yield and qualified rate of medicines. The development and application of powder preparation technology and metal powder materials have an important impact on the preparation process and preparation quality of the pharmaceutical industry.
Application of powder technology in the pharmaceutical industry In traditional
Chinese medicine preparations and synthetic drugs, traditional Chinese medicine biological powder materials and metal powders have been widely used. At present, for mineral drugs, precious drugs and traditional Chinese medicines with special properties, hammering and ball milling methods are generally used in China, which can not only make the drugs reach a certain particle size, but also maintain the inherent pharmacodynamic basic substances of traditional Chinese medicine. The particle size, quality difference, mixing uniformity, tablet strength, etc. of traditional Chinese medicine are mostly related to powders. For medicinal materials processed by ultrafine powder technology, the purpose of controlling the quality of solid preparations can be achieved by controlling the fluidity, filling and compression forming properties of solid preparations, while their disintegration, solubility and bioavailability are related to the powder properties of each material in the drug prescription. The smaller the particle size of powder materials for Chinese medicine, the better. The Chinese medicine powder materials with a median particle size of about 15μm have a high cell wall breaking rate, which is conducive to the release and absorption of drugs; the drug dissolution rate is high in vitro. In the process of compound Chinese herbal medicine pulverization, the homogenization of each active ingredient is conducive to retaining the biologically active ingredients and improving the drug effect; it is easy to shape and easy to use, which is conducive to exerting the efficacy of drugs and improving the utilization rate of medicinal materials. Ultrafine Chinese medicine powder.
When synthesizing Western medicine, metal powder materials with a median particle size of about 75μm are generally used for chemical reactions such as catalysis, reduction and oxidation. In recent years, with the current climax of the modernization of Chinese and Western medicines and the development of nanotechnology, powder technology has also had a broader development space, providing new methods and approaches for the research of modern drug delivery systems, and significantly improving the absorption rate and amount of the active ingredients of each component by the human body.Application of metal powder materials in the pharmaceutical industry
01 Zinc powder material
The most commonly used metal powder material in medicine is zinc powder with a median particle size of about 75μm and prepared by distillation. The zinc powder has uniform particle size, high purity, strong activity, and low mass fraction of other impurity elements. It can be used as a reducing agent to prepare various drugs, such as salicylic acid, aminopyrine, gliclazide, indomethacin, cephalosporin, etc.
The particle size of zinc powder has a great influence on the yield and qualified rate of pharmaceutical intermediates. Too large particle size will lead to incomplete chemical reaction. Only the surface of the spherulite reacts with the chemical agent, and the internal reaction cannot be fully carried out. In addition, the zinc powder will agglomerate into blocks under the action of the agent, and even cause safety accidents. The purity of zinc powder also plays a decisive role in the degree of reaction and product yield. In some pharmaceutical processes, high-purity and high-activity zinc powder is needed to replace hydrogen or carry out chemical synthesis. On the one hand, it can make full use of raw materials, effectively control costs, and reduce secondary environmental disposal costs; on the other hand, it can improve product yield, which can not only reduce hazardous solid disposal costs, but also improve economic benefits. The mass fraction of trace elements such as lead and cadmium impurities must be low enough so that the heavy metals in the medicine will not exceed the standard when preparing Western medicine, thereby not harming the patient's body. Therefore, the mass fraction of trace elements is crucial to the edibility of medicines.
Zinc powder is used as a catalytic reducing agent, mainly to catalyze the reduction of strong alkaline media or reduce nitro groups to amino groups, aldehydes or ketones to alcohols, etc.
02 Iron powder materials
The medicinal value of iron powder can be traced back to the book "Supplement to Materia Medica". Iron powder with a particle size of about 75
μm has a weak electron-donating ability and is suitable for easily reduced groups. Iron powder can be used to prepare synthetic drugs such as paracetamol, vitamin B6, and anti-inflammatory drug benoxaprofen. Its particle size, purity, and trace element mass fraction are the core factors affecting the pharmaceutical process.
Typical applications of iron powder are, for example, catechol, which is an important raw material intermediate in fine chemical sectors such as medicine, petrochemicals, and spices. It is usually synthesized by peroxidation of phenol to synthesize catechol; when iron powder is used as a catalyst for phenol hydroxylation, its preparation is simple, cost-effective, reaction conditions are mild, the catalyst dosage is small, and the activity is good. Compared with zinc powder, in some catalytic reduction reactions, the yield of the product is lower when iron powder is used as a reducing agent. Therefore, it is necessary to select appropriate powder materials according to the catalytic reduction of the drug. As a catalytic reducing agent, iron powder mainly reduces nitro groups to amino groups, carbonyl groups to hydroxyl groups, and prepares thiophenol compounds.
03 Aluminum, tin and other metal powder materials
Aluminum, tin and other metal powder materials are not common in the preparation of drugs. The main reasons are as follows:
(1) Aluminum powder and tin powder are more dangerous during preparation and use;
(2) The activity of the two is relatively low, far less than that of zinc powder in the replacement reaction of pharmaceutical preparation;
(3) The density is relatively low, and it is difficult to be compatible with pharmaceutical reagents and undergo chemical reactions.
Aluminum powder and tin powder are mainly used for catalytic reduction in the pharmaceutical industry. For example, nitrobenzene is reduced by aluminum powder in a sulfuric acid medium to obtain hydroxyaniline (aniline), and at the same time rearranged into p-aminophenol (PAP, used in the pharmaceutical industry to synthesize paracetamol, clofibrate, etc.); under acidic conditions, tin can reduce the nitro group to an amino group, such as the intermediate of the anthelmintic methylaminobenzeneamidine and the intermediate of aminobenzoic acid (mainly used for hemostasis in acute or chronic bleeding situations).
Under some special conditions, magnesium can be used instead of zinc for reaction. Organic magnesium reagents are highly active and can be used for reactions that organic zinc cannot perform.
In addition, metal oxide powders can also be used in pharmaceutical products. For example, zinc oxide powder materials have good activity and high purity. In the pharmaceutical industry, they can be used as raw materials for adhesive plasters, baby powders, zinc pastes, etc.; iron, copper, and aluminum oxide powder materials are also widely used in the pharmaceutical industry.