Selection and design of a hammer pulverizing system for continuous, flexible and closed production of oral solid preparations

[technical article of China Pharmaceutical network] the challenge for the pretreatment of raw and auxiliary materials of oral solid preparations in particle size distribution is to achieve the distribution accuracy as high as possible, so as to maintain a constant content of active ingredients in the subsequent preparation process In addition to the micro pulverization specially designed for the customized rotational speed range of the product, the temperature maintenance and crystal stability of the active ingredients and excipients lay the foundation for the granulation, tablet pressing and capsule filling of the back-end of the oral solid preparation, and the previous micro pulverization process of the oral solid preparation is crucial In addition to dust removal, pre-treatment can solve dust, health and environmental protection problems through dust-free feeding or automatic feeding system, especially for occupational exposure band, OEB) other micronization processes such as anti-tumor, hormone and toxic drugs, so the modular, flexible, continuous and closed production process of oral solid preparation pretreatment is particularly urgent (occupational exposure band (OEB) in the traditional process, micronization is often to use the API active ingredients and auxiliary materials to form a vortex mixed air flow in a strong position through the traditional 20b / 30b dynamic and static gear grinding form Different sizes, shapes and properties in the chamber through friction and collision, constantly reciprocating until the mesh diameter fineness This process is established without considering many factors such as temperature rise, OEL value, airtightness, crystal protection, etc during the comminution process As a result, the crystal form of active ingredient of API is destroyed; temperature rise causes physical and chemical changes of active ingredient; health of operators is challenged; pollution of clean area is threatened (diversity of HM400 hammer pulverizing system) fandu dust-free oral solid pulverizing system uses the internationally recognized advanced sterile hammer pulverizer head (hammer) Mill-fd400) as the core part of the pulverization, improves the particle size distribution and crystal shape in the above hammer pulverization process; at the same time, on the basis of the original grinding head technology, through the outer wall contact cooling and cooling, to ensure the constant temperature in the continuous feeding / feeding process Active pharmaceutical ingredients can enter the equipment through vacuum conveying or glove box feeding According to the characteristics of the product, the speed of the crusher can be adjusted to meet the requirements of good particle size The material usually stays in the crusher for a few seconds, It can achieve the required uniform distribution without staying in the chamber In the front end of the crushing chamber, a quantitative feeding device can be used to ensure the stability and uniformity of the materials entering the chamber for crushing In general, the lower end of the crushing adopts IBC turnover barrel to facilitate the flexible docking with the mixer The intermediate materials are often connected at the lower end with a weighing and sub loading mechanism According to the needs, the whole hammer type can be used Nitrogen can be added into the pulverizer for inerting The continuous production of oral preparation (HM400 hammer pulverizing system with temperature and pressure detection and nitrogen inerting) firstly reduces the complex cleaning steps and intermediate product storage time At the same time, due to the improvement of production efficiency, the size of fandu hammer oral solid preparation pulverizer is greatly reduced on the basis of the traditional pulverizing unit At the same time, the static or rotating nozzle cleaning device can be used according to the needs, and the nozzle can be designed to be retractable, so as to reach all areas in the container conveniently After cleaning, the equipment can be blown by hot air and dried thoroughly for the next use, which is also a challenge for the hammer crusher seal to enter the gas with a certain pressure (HM400 hammer pulverizing system with CIP / SIP) however, not all active ingredients and auxiliary materials are suitable for continuous process production, and the development from batch process to continuous process requires high start-up capital - process equipment The first investment of process analysis PAT system and controllable system is very high - often higher than that allowed by economic conditions At the same time, the active ingredients are usually produced by a proven process Therefore, in the pharmaceutical industry, the solid preparations are usually still produced by a classic batch process In terms of dust control, in order to ensure the strict sealing of incoming and outgoing materials, it is necessary to consider the release of cavity pressure and the flow of internal air flow Fandu uses the negative pressure dedusting device on the basis of the original hammer grinding head, which is a dedusting and filtering device with automatic back blowing system The device generates negative pressure near the discharge port, which accelerates the downward flow of materials; the internal dust removal filter will be automatically cleaned by the back blown air pressure pulse every other period of time, which ensures that the filter chamber is always clean, and the materials sucked out will also return to the barrel, which will not cause waste The pneumatic control system is directly connected to the filter chamber, so the whole filter system operates independently without interference; the dedusting system adjusts parameters such as back blowing and dedusting time, interval time, etc through PLC control, to meet the needs of different particle size materials In recent years, the increasing activity of drugs (so-called hpapi, active drug ingredients) has led to the protection of production personnel by special primary and secondary measures In addition, because a very small amount of drugs have a very good effect, we must avoid cross contamination with other substances Fandu dust-free oral solid pulverizing system is optimized, and the material feeding adopts the closed vacuum conveying mode, so as to achieve the requirements of dust-free, continuous and closed standards, and to reach the required threshold specified by the workplace The shaft seal adopts air seal or air blast to prevent the product from leaking out of the equipment and reduce the wear of the seal (HM400 hammer pulverizing system for automatic feeding and mixing in the production of oral solid preparations) According to the concept that quality comes from design (QBD), airtightness should be a part of the design of high active pharmaceutical production process equipment As far as the mechanical structure is concerned, the airtight pulverizing system composed of airtight pulverizer and related auxiliary equipment designed to meet the requirements of high active pharmaceutical pulverization adopts airtight isolation, negative pressure control, airtight transmission, Bibo, WIP cleaning and other prevention measures Dust and airtight technology can achieve the grinding operation of highly active drugs with OEL<10 μ g/m3 or even more However, the actual level of OEL of pharmaceutical preparations is related to the product process formula, or even particle size and other properties For different drugs, the same equipment may achieve different OEL values, so for a certain drug, the airtight performance that the equipment can achieve needs to be determined by the test results.