Yao Da
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Yao Da
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Total6464 Words|Recommended Reading21 Minutes
From | Chinese Pharmaceutical Technology
Drying is a crucial step in the preparation process of Traditional Chinese Medicine (TCM) pills, and the choice of drying method and optimization of process parameters directly determine the quality of the dried TCM pills. However, there are still limitations in the selection of drying methods, low intelligence of drying equipment, and poor suitability of equipment, which need to be addressed through in-depth research on the drying mechanisms of pills, integration of precise sensing technologies, and computer intelligent control technologies to achieve intelligent drying equipment that meets GMP production requirements.
TCM pills refer to spherical solid preparations made from finely powdered medicinal materials or extracts combined with suitable binders and excipients. Depending on the excipients used and the preparation methods, TCM pills can be categorized into types such as honey pills (mi wan), water honey pills (shui mi wan), water pills (shui wan), paste pills (hu wan), wax pills (la wan), concentrated pills (nong su wan), and micro pills (wei wan). TCM pills have their own advantages as a dosage form, being natural sustained-release preparations that are traditional yet not outdated, making them an ideal choice for clinical research and application in TCM. In recent years, with the development of pill-making equipment, techniques, and new excipients, the volume of TCM pills can be significantly reduced, and their quality continuously improved, especially for the production of sustained and controlled-release preparations, where many chemical drugs are made into micro pills, thus injecting new vitality into this traditional dosage form.
The preparation methods for TCM pills mainly include the plastic method and the general method. The appearance of the formed wet pills should ensure uniform roundness, no cracks, no sticking, and consistent color, with moisture content varying by type from 20% to 40%. According to the standards for TCM inspection, the moisture content of honey pills should be ≤15%, water honey pills and concentrated water honey pills ≤12%, and water pills, paste pills, and concentrated water pills ≤9%. Therefore, the drying and dehumidification of TCM pills is an essential process in their preparation.
Currently, the industrial production process for drying TCM pills mainly relies on traditional drying equipment that is low in investment cost, simple in structure, and relatively mature in technology. However, to improve production efficiency, enhance the quality of dried TCM pills, save energy, and reduce environmental pollution, researchers are continuously exploring new technologies and equipment suitable for drying TCM pills. This article analyzes and discusses common drying technologies for TCM pills, new technologies and equipment with development potential, and existing issues in the drying of TCM pills.
1. Quality Evaluation Indicators for Drying TCM Pills
▍Appearance of Dried Pills
Overall, the dried pills should be uniformly round and not cracked. Different types of pills have different requirements; for example, honey pills should remain delicate and moist after drying, with moderate hardness, while concentrated pills should maintain a smooth and uniform appearance without cracks.
A reasonable drying process is crucial to ensure the appearance requirements of the pills after drying. Honey pills should be dried at a pressure of 80 °C or lower, and when they are about 50% dry, they should be frequently turned to maintain their round and soft appearance; otherwise, if the moisture is too low, the surface of the pills will become rough. Water pills should be dried at a pressure of 80 °C or lower, with uniform heating to prevent cracking. Paste pills should be dried at temperatures below 60 °C or placed in a ventilated area to dry in the shade, as the internal moisture of paste pills evaporates slowly. If dried at high temperatures too quickly or exposed to sunlight, the surface of the pills may dry while the inside remains soft, leading to cracks or breakage. Pills containing volatile components should be dried at low temperatures below 60 °C, using a gradual heating method, slowly increasing to around 60 °C without turning the pills or allowing cold and hot air convection until they are about 80% dry, at which point air circulation can be initiated for temperature exchange. This is because volatile components will evaporate with moisture at high temperatures, and the powder of drugs with many volatile components is very loose; if heat exchange is too rapid, the binding between the powders will not be tight, making them prone to cracking, affecting the quantity and properties of the pills.
▍Moisture Content of Pills
The Chinese Pharmacopoeia specifies moisture content requirements for different types of finished pills to maintain a low moisture content to improve drug stability and ensure drug quality. The 2015 edition of the Chinese Pharmacopoeia outlines five methods for determining moisture in TCM: the Karl Fischer method, drying method, vacuum drying method, toluene method, and gas chromatography method.
▍Dissolution Time
Dissolution refers to the process by which pills dissolve and disintegrate in water, with all fragments passing through a basket screen, or if they do not pass through the screen but have softened without hard cores, they can be considered qualified. Unless otherwise specified, small honey pills, water honey pills, and water pills should dissolve completely within 1 hour; concentrated pills and paste pills should dissolve within 2 hours; the dissolution time for micro pills is determined according to the type of pills; large honey pills are not subject to dissolution time checks.
All TCM pills contain some powdered medicinal materials, and the release of effective components must go through stages of wetting, permeation, dissolution, and diffusion based on the dissolution of the pills. Many factors affect the dissolution time of pills, such as the properties of the materials, the fineness of the powders, the properties and amounts of excipients, the moisture content of the pills, the speed of pill formation, the size of the pills, and the drying methods and temperatures used.
▍Microbial Limits
Microbial contamination in TCM pills originates from raw materials, the preparation process, packaging, and transportation. Effective control of microbial counts can be achieved by focusing on the pre-treatment of raw materials, using clean and qualified binders, ensuring hygiene during the pill-making process, using qualified packaging materials, and strengthening terminal sterilization of finished products.
▍Content of Indicator Components
The change in the amount of indicator components during the drying process of TCM pills is one of the most important indicators for evaluating the quality of dried products. The types of indicator components in TCM pills vary, such as alkaloids, glycosides, volatile oils, and organic acids. The drying process usually involves heat transfer and mass transfer, so there may be a loss or chemical transformation of indicator components, ultimately leading to a decrease or loss of efficacy after drying. Choosing a reasonable drying method and equipment and optimizing drying process parameters can minimize the changes in the amount of indicator components from the beginning to the end of the drying process.
2. Analysis of Drying Mechanisms for TCM Pills
▍Drying Process of TCM Pills
The drying process of TCM pills is divided into three stages: preheating stage, constant rate stage, and falling rate stage. The preheating stage is the initial heating process of TCM pills at the start of drying, where the temperature of the pills continuously rises, and the internal moisture evaporation rate accelerates. Therefore, the preheating stage at the beginning of drying is a brief period of accelerated drying rate.
When the temperature of the pills reaches the wet bulb temperature under the corresponding drying conditions, the temperature no longer increases, and the drying rate remains constant, entering the constant rate stage. During the constant rate drying stage, the surface of the pills remains moist, and there is sufficient moisture migrating from the interior to the surface, so the drying rate during this stage is mainly controlled by external factors, such as the temperature, humidity, flow rate, and direction of the drying medium, as well as the physical state of the pills.
As drying progresses, the moisture content of the pills continues to decrease, the surface no longer remains moist, and the surface temperature rises from the wet bulb temperature, gradually approaching the temperature of the drying medium, entering the falling rate drying stage. The drying rate during the falling rate stage is mainly controlled by the rate of internal moisture migrating to the surface, rather than the evaporation rate of surface moisture, so the form and rate of moisture migration from the inside to the outside during this stage are mainly determined by the internal structural characteristics of the pills. The forms of moisture migration during the falling rate stage mainly include diffusion, capillary flow, and internal pressure generated by the shrinkage during the drying process.
▍Characteristics of Drying Processes for TCM Pills
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Temperature Factors
Temperature is one of the main influencing factors controlled by external factors during the constant rate drying stage. Increasing the drying temperature can enhance heat transfer and increase the drying rate during the constant rate stage. However, most pharmacological active components in TCM pills are heat-sensitive; for example, the phenolic compounds in Liu Wei Di Huang Wan dissolve in hot water, and if the drying temperature is too high, these components will be lost with the water vapor. Therefore, the drying temperature should not exceed 70 °C. Additionally, excipients added during the pill-making process may also have temperature requirements; for instance, the gel point of PEG 6000 used in Yuan Hu Zhi Tong Di Wan is 53–58 °C, and excessive drying temperatures can lead to deformation of the pills, thus vacuum drying at 35 °C is preferred.
During the hot air drying process of TCM pills, excessively high initial drying temperatures can cause the surface of the pills to dry too quickly, leading to a hard crust that prevents internal moisture from migrating to the surface, hindering the continuation of drying. Additionally, high internal vapor pressure may cause the pills to explode or crack, directly affecting product quality. Bai Na Ren found in research on the drying of Mongolian water pills that excessively high drying temperatures lead to the formation of a hard layer on the surface, resulting in extended dissolution times that do not meet requirements. Therefore, during the drying process of TCM pills, temperature control should balance drying rate and product quality, leaning towards ensuring product quality.
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Microbial Control
As solid oral preparations, TCM pills have strict limits on microbial counts. The 2015 edition of the Chinese Pharmacopoeia clearly states that pills containing raw powdered medicinal materials and not containing fermented raw powders should have a total aerobic count limit of 3×104 cfu/g and a total mold and yeast count limit of 100 cfu/g.
The drying of TCM pills, as the final process in pill production, is particularly critical for controlling microbial limits. The control of microbial counts during the drying process is mainly achieved through prevention of contamination and sterilization. Preventing contamination of the pills during drying is related to the cleanliness of the production environment, drying equipment, and operator practices; for example, drying equipment in non-clean environments should be equipped with high-efficiency filters to purify the air entering the drying equipment.
Simultaneous sterilization during the drying process of TCM pills should be achieved through specific drying technologies and processes or by adding sterilization units for combined application. In summary, microbial control is a factor that should be considered during the drying process of TCM pills.
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Holding Methods
The holding method during drying directly determines the state of the material being dried within the dryer. Based on whether the material is in motion, it can be classified as dynamic or static. Dynamic drying can increase the contact probability between the pills and the heat medium, enhancing heat transfer efficiency and accelerating drying, and appropriate movement trajectories help maintain the spherical shape of the pills.
Micro pills and small pills, due to their smaller size and mass, benefit from dynamic holding methods that not only accelerate drying and ensure uniform heating but also minimize shape distortion. Equipment such as rotary drum dryers, double-cone rotary dryers, and fluidized bed dryers can be used. However, TCM pills are formed from powdered drugs bound together with excipients, and for larger pills, the reduction of internal moisture can change the binding properties. If excessive vibration or inappropriate vibration methods are applied, it may cause the pills to disintegrate and lose shape. For loose pills like fennel pills, heating during drying can cause shrinkage, and if excessive vibration is applied, it may lead to cracking. Therefore, static holding methods are generally used for TCM pills. When determining the drying holding method for TCM pills, it is essential to fully understand the physical properties of the pills to achieve optimal results in drying efficiency and product quality.
3. Common Drying Processes and Equipment for TCM Pills
▍Box-Type Hot Air Drying
Intermittent operation of a box-type dryer at atmospheric pressure involves spreading the prepared TCM pills on drying trays placed on fixed racks or carts within the drying chamber. If the drying workshop is a non-clean space, the air is filtered through a high-efficiency filter and heated before entering the dryer, then passes horizontally over the surface of the TCM pills for drying.
Box-type dryers are characterized by simple structure, ease of manufacture, simple operation, and high adaptability, making them widely used in small and medium-sized TCM pill production facilities, especially suitable for drying expensive TCM pills, small batches, high drying requirements, and situations where drying conditions such as airflow, temperature, and humidity need to be changed frequently. Ma Xinhua and others optimized the drying process of Qi Ju Di Huang Wan in a hot air circulation oven, selecting the moisture content and dissolution time of the dried Qi Ju Di Huang Wan as evaluation indicators, and the results indicated that the optimal drying conditions were a temperature of 60 °C, drying time of 28 hours, and material thickness of 2 cm. However, since box-type drying of TCM pills generally uses static holding methods, there may be issues with uneven drying leading to uneven moisture distribution and color discrepancies in the TCM pills, and the manual handling of materials during loading and unloading can increase labor intensity, worsen operating conditions, and prolong drying times.
▍Vacuum Drying
The vacuum drying technology for TCM pills involves placing wet pills in a sealed negative pressure environment and appropriately heating them to evaporate moisture at lower temperatures, with the vacuum system removing the water vapor. The vacuum dryer for TCM pills uses heat conduction to heat the material, with heat transfer media typically being steam, hot water, or heat transfer oil. The closed space combined with the vacuum system not only lowers the boiling point of moisture in the pills but also allows for the timely removal of evaporated water vapor from the drying chamber, achieving efficient low-temperature drying. Suitable forms of vacuum dryers for TCM pills include box-type vacuum dryers and double-cone rotary vacuum dryers. Jia Jiangping studied the use of double-cone rotary vacuum dryers for drying micro pills, evaluating the working principle, factors affecting drying speed, and drying examples, concluding that the quality of products dried using vacuum methods is superior to those dried at atmospheric pressure. However, the heat transfer efficiency of the heat conduction method is affected by the contact area between the heating surface and the pills, so for larger pills using static holding methods, the contact may be point-like, leading to uneven drying and low drying efficiency.
▍Box-Type Microwave Drying
The box-type microwave dryer consists of a rectangular resonant cavity, input waveguide, reflector, and stirrer. Microwaves are transmitted through the waveguide into the rectangular box, with each side dimension greater than 1/2 wavelength, allowing for reflection of waves from different directions. The TCM pills being dried can absorb microwave energy from all directions within the cavity, leading to heating and drying.
Microwave drying refers to a method where moisture within the wet material absorbs microwaves of specific frequencies, generating thermal effects that cause evaporation, ultimately drying the material.
Since moisture is the primary medium for absorbing microwaves, its uniform distribution within the wet material allows for even heating during the drying process, thus avoiding surface hardening and uneven drying commonly seen in conventional drying processes.
Due to its high energy efficiency, low drying temperature, short drying time, no preheating required, and no residual heat, which does not affect the color, taste, aroma, or structure of the dried material, as well as its sterilization and pest control advantages, microwave drying technology is widely applied in the drying of wet TCM pills. Lu Pengwei and others conducted experimental verification of the microwave drying process for Liu Wei Di Huang Wan, comparing the moisture content, dissolution time, and microbial limits of the pills after microwave drying, concluding that microwave drying is stable and reliable, and certain measures should be taken to improve the differences in moisture content and dissolution time of pills at different positions on the conveyor belt.
Static holding methods for box-type microwave drying require strict control over drying time and temperature, and uneven initial moisture distribution in the pills can easily lead to localized charring and undried phenomena. If horizontal rotating loading racks and basket-type rotating loading racks are used, allowing for overall dynamic drying of the material, these issues can be effectively prevented. However, the dynamic basket loading method reduces the effective loading space within the box-type dryer and increases the complexity and cost of the equipment.
4. Issues and Countermeasures in Drying TCM Pills
▍Limitations in the Selection of Drying Methods
TCM pills have a multi-component characteristic and often contain heat-sensitive components that can decompose or be lost at high temperatures. Therefore, their drying temperature cannot be too high, leading to certain limitations in the selection of drying methods. The requirements for low-temperature drying significantly impact drying efficiency, as temperature is one of the main driving forces for heat and mass transfer during the constant rate drying stage. Lowering the temperature significantly reduces the drying rate during this stage, resulting in many TCM pill manufacturers taking 12 to 24 hours for industrial production using 50 to 60 °C hot air circulation drying ovens, with some varieties even exceeding 30 hours. Additionally, the drying process using ovens or drying rooms is static, and to prevent deformation or cracking of the pills due to uneven heating, manual turning of the pills is often required, increasing labor costs. Thus, the insufficient capacity of the drying process segment has become a bottleneck for pharmaceutical companies looking to expand production scale.
To improve the thermal efficiency of low-temperature hot air drying processes, improvements can be made through reasonable design of airflow organization and the addition of tail heat recovery systems. A reasonable airflow organization should ensure that hot air fully contacts the material to enhance heat and mass transfer efficiency, and properly manage the temperature and humidity gradient formed by hot air during the drying process to achieve energy cascading utilization.While effectively removing moisture from the pills, hot air should also be reasonably recovered to improve thermal efficiency.
To address the issues caused by static drying in ovens or drying rooms, improvements can be made to the material holding forms in drying equipment, such as using mechanically driven vibrating beds, rotary double-cone cylinders, and cylindrical rollers, which can allow the pills to be in motion during drying, ensuring more uniform contact between the material and the heat medium and further shaping the pills through rolling along the walls of the dryer to improve appearance quality.
▍Low Intelligence of Drying Equipment
Drying equipment for TCM pills must not only meet various production process indicators for drying pills but also comply with GMP requirements, which include considerations for equipment strength, precision, surface roughness, and operational reliability, as well as ease of disassembly and cleaning, and the absence of sanitary dead corners.
In recent years, with the continuous development of sensing technology and mechanical manufacturing processes, TCM pill drying equipment has made significant progress in product stability and appearance. However, there is still considerable room for development in the intelligence of the equipment. The physical parameters of TCM pills during the drying process, such as moisture, odor, appearance, and the amount of indicator components, are still primarily measured through sampling, leading to drying processes being set before drying begins and remaining unchanged until the end. The inability to obtain timely information on the changes in physical parameters during the drying process results in an inability to make real-time adjustments to drying process parameters, which can compromise pill quality and even lead to energy waste.
The intelligent development of drying equipment for TCM pills may draw inspiration from intelligent technologies used in other drying equipment, such as bionic systems, computer vision technology, microwave dielectric spectroscopy, near-infrared reflectance spectroscopy, magnetic resonance imaging technology, ultrasonic technology, and electrostatic sensing technology, which are being researched and gradually applied in the food drying field. The drying of TCM pills is a complex process, and achieving multi-faceted intelligence in drying equipment will require ongoing research and exploration.
▍Suitability of Drying Equipment Needs Improvement
The promotion and application of new drying equipment for TCM pills face various unsuitabilities. The new GMP implemented in China in 2011 has imposed stricter regulations on the design, manufacture, installation, validation, and quality control of pharmaceutical equipment, posing challenges for pharmaceutical equipment manufacturing enterprises.
Some drying equipment for TCM pills that is structurally simple, has rough processes, high energy consumption, and low cost is gradually being eliminated due to non-compliance with new GMP requirements. Meanwhile, some new drying equipment based on new technologies faces challenges such as immature technology, complexity, and high costs, making it difficult to cope with large-scale industrial production applications. In summary, drying equipment for TCM pills should be based on general equipment, upgraded and transformed using advanced concepts and technologies, and designed and manufactured with high efficiency, low consumption, and quality to meet the needs of industrial production of TCM pills.
5. Conclusion
Drying, as a key operational unit in the preparation process of TCM pills, directly affects the quality of the finished product. Different categories of TCM pills require different drying methods based on the physical properties of the pills and production conditions. Traditional drying technologies for TCM pills each have their advantages and disadvantages, and the technology has matured to a certain extent. In contrast, some new low-energy, low-cost, and high-efficiency drying technologies and equipment are rarely applied.
New drying technologies such as heat pump technology, combined drying technology, and high-voltage electric field drying technology have advantages in improving product quality in the drying of TCM pills, but they still face practical issues such as high investment costs and immature technology applications. Multi-layer vibrating dryers, which fully consider the heat and mass transfer theory during the drying process, improve energy utilization, and reasonably control the temperature and humidity gradients of the drying medium, ensuring the quality of the pills while maintaining a simple structure, have great development prospects.
Overall, drying equipment for TCM pills is developing towards high efficiency, energy saving, environmental protection, and intelligence. With the continuous deepening of research on the drying mechanisms of pills, the ongoing development of sensing technologies, and the effective integration of computer control technologies with drying equipment, the drying processes and equipment for TCM pills will continue to transition from experimental to production applications, becoming more intelligent and compliant with GMP production requirements.
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