Application of spray drying technology in the production of oral solid preparations

The spray drying technology uses a spray method to disperse the material in a hot air stream in a mist state. The material is in full contact with the hot gas to complete the heat transfer and mass transfer process in an instant, so that the solvent (including water and organic solvent) evaporates rapidly. For gas, achieve the purpose of drying. Spray drying technology is widely used in the pharmaceutical industry in China. It is widely used in the field of oral solid preparations, and is often used for the drying of easily decomposable drugs in high heat sensitive medicines and liquid concentrates. The obtained product has fine particle size, uniformity, good fluidity and fast solubility.

Spray dryer features and classification

A spray dryer is a drying device that directly dries a solution or suspension into solid particles. The dry product can be directly obtained from the liquid, eliminating the unit operations such as evaporation, crystallization, separation and pulverization, and can be continuously and automatically produced, and the operation is stable. By adopting the drying method, the gas-solid two-phase contact surface area in the spray dryer is large, the drying time is short, and the drying time is generally 5 to 30 s, which is suitable for drying the heat sensitive material. The product obtained by drying is of good quality, and particles of 30 to 50 μm can be obtained, and the product has good fluidity and fast solubility. The disadvantage is that the dryer has a large volume and a low heat transfer coefficient, resulting in low thermal efficiency and high power consumption. There are many classification methods for spray dryers. According to the flow direction of gas and liquid, it can be divided into parallel flow, counter flow and mixed flow; according to the installation method of atomizer, it can be divided into upper spray type and lower spray type; The structure of the device can be divided into centrifugal type, pressure type and air flow type; according to whether the heating gas is circulated, it can be divided into open type, partial circulation type and closed type.

Basic process of spray drying (closed)

The liquid is atomized by the atomizer and dispersed into fine mist droplets into the drying chamber. At the same time, the heating gas is sent to the heater through the blower to heat up, and then enters the drying chamber. The liquid droplets are thoroughly mixed and contacted with the hot gas in the drying chamber. The liquid in the droplets evaporates instantaneously into a gas, which is dried into fine particles. The mixed gas-solid two-phase is sucked into the cyclone by the induced draft fan, the two phases are separated, the solid material is settled to the bottom collector, and the gas phase is led to the dust filter to capture the escaped material. After the filtered gas phase is condensed by the condenser, the solvent carried in the gas phase becomes a liquid, which can be collected and used, and the gas as a carrier is dried and then recycled in the system. The flow chart is as follows:

Process requirements for oral APIs

There are many kinds of oral solid preparations, and the specific process requirements are also very different. In the process of designing and manufacturing the spray dryer, it is better to design different designs for different varieties to achieve the best condition for equipment and process. Solid formulation production When using a spray dryer, some of the requirements listed below are often raised:

1. Cleanliness requirements (the following seven subheadings should be changed to italics) The main process of API production needs to be carried out in a 100,000-level clean environment. Spray drying is an important process of quality control. The part of the spray dryer that contacts the material should be made of stainless steel. For materials with strong acid corrosion, 316L stainless steel is the best choice. Drying chamber, cyclone separator, filter and other parts that directly contact the material should have smooth inner wall, no dead angle, easy to clean, easy to disassemble, and easy to clean. Spray dryers tend to be bulky, so they cannot be placed in a clean area as a whole, and often only the part where the material is collected is placed in a clean area. This requires a good system sealing performance to prevent external contamination from being systematic.

2. Avoiding stick wall sticking is still a prominent problem that hinders the normal operation of spray dryers. The spray drying process of solid preparations (especially Chinese medicines) is particularly obvious. The sticky wall of the material is not only unfavorable for the collection operation, but as time goes on, the sensitive sticky wall material will deteriorate and become a non-conforming material. From a process point of view, the solution includes selecting the right solvent, adding the excipients, and changing the process parameters. However, there is not much room for adjustment of these methods, so a fundamental solution must be sought from the perspective of the equipment. Experts at home and abroad have conducted in-depth research on the problem of sticking and agglomeration in the drying process. It is agreed that the main cause of sticking is the wall temperature. The following are five possible ways to prevent sticking walls: * Use a wall-mounted drying tower with air cooling to keep the wall temperature below 50 °C; * Introduce the secondary air cooling tower wall through the tangential direction of the tower wall vortex sheet; * Install an air broom consisting of a row of nozzles near the inner wall of the tower and make it slowly rotate along the tower wall; * increase the air hammer on the tower wall, force the sticky material to be detached by the hammering of the air hammer; * increase the processing Accuracy, polished inside the tower can also reduce the sticking wall.

3. Self-control performance Spray drying is a continuous production process with more control points. For example, the control points of the closed circulation system include: feed concentration, feed rate, inlet speed, inlet air temperature, system pressure, differential pressure of each component, gas purity detection, etc., relying on traditional manual adjustment is very difficult. A good automatic control system can make the whole spray drying system run smoothly, reduce the product's unqualified rate and reduce safety hazards. At present, domestic products are relatively backward in terms of self-control, while some advanced equipments in foreign countries, such as the spray dryers of Danish Nero Company, are already very mature in terms of self-control.

4. Drying effect Since the oral drug substance needs to further complete the preparation process, different requirements are imposed on the physical properties of the spray-dried product in terms of improving the effect of the preparation and the absorption effect of the final drug. First of all, the moisture content is the first indicator of dry products, generally required to be controlled within a certain range, not too high or too low. Secondly, the dispensing of drugs generally controls the volume according to the volume, which requires that the bulk density of the product is stable and the fluidity of the product is good. Oral granules often require fast solubility. In general, by varying the dispersion of the atomization or by appropriately changing the operating conditions to control the drying rate, products having different bulk densities can be produced, but the magnitude of the variation is limited. One technique worth mentioning in improving physical properties is foam spray drying, in which the feed liquid is first foamed and then spray dried. The method was originally proposed to improve thermal efficiency and was later used to adjust the physical properties of the product. It has been proved that the product prepared by foam spray drying has large particle size, is porous, has many depressions, has a rough surface, and has good fast solubility. In addition, there are some special requirements for oral drug substances, such as: particle shape. Some require spherical particles with a uniform particle size. Generally, particles of different shapes can be obtained by changing the atomization method. Before selecting a spray dryer, it is best to conduct a parameter optimization experiment with the assistance of the equipment manufacturer to determine an optimal combination of parameters to ensure the drying effect of the sprayed drug.

5. Protection measures Due to the different nature of the drugs, some higher requirements are also placed on the protection design of the equipment. Materials dissolved in organic solvents require that the entire system must meet explosion protection requirements when dry. Explosion-proof type should be selected when designing motors, instruments, control valves and other accessories. In addition, in order to prevent the solvent and air from mixing into an explosive gas, the system cannot adopt an open type, but a closed circulation system must be used, and the carrier should be an inert gas such as nitrogen. In addition, some of the easy-to-oxide materials are dried, and a closed circulation system using nitrogen as a carrier is also used.

6. Environmental protection spray drying products are fine particles. In order to meet the requirements of environmental protection, it is not enough to use a cyclone separator to separate products and purify exhaust gas. It is generally necessary to purify with a bag filter to make the exhaust gas The dust content is less than 50mg/(nm)3 gas; or the wet scrubber can reduce the dust content of the exhaust gas to 15~35mg/(nm)3 gas. When using nitrogen as the carrier, the system should be sealed and the exhaust port should be led to the outside.

7. Reduced cost The hot air inlet temperature is 250-500 °C in the cocurrent operation and 200-300 °C in the countercurrent operation. The outlet temperature after atomization drying is generally controlled at 60-100 °C. Spray drying has a low heat utilization rate, and industrial scale spray dryers generally have a thermal efficiency of 30% to 50%. Spray drying with waste heat recovery abroad can achieve a thermal efficiency of 70%, but this equipment is only economically meaningful when the production capacity is greater than 100kg (water) / h. However, when a nitrogen carrier and an organic solvent are used, a closed circulation system can be used, and the nitrogen can be recycled, and the solvent can be condensed, thereby effectively reducing the production cost. Domestic spray dryer manufacturers are constantly improving their technical level and solving the technical problems of spray drying in the field of oral APIs. I believe that in the near future, we will be able to produce more suitable, high quality and low price products, so that our country Spray drying technology has reached the world's leading level.

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